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pmid:36915600

Extracellular matrix-based gene signature for predicting prognosis in colon cancer and immune microenvironment.

Ruoyang Chai · Zhengjia Su · Yajie Zhao · Wei Liang

Translational cancer research · 2023 doi:10.21037/tcr-22-2036

Paper

complete

Experiment

complete

Data

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Analysis

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title
Extracellular matrix-based gene signature for predicting prognosis in colon cancer and immune microenvironment.
doi
10.21037/tcr-22-2036
pmid
36915600
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[0]
Ruoyang Chai
[1]
Zhengjia Su
[2]
Yajie Zhao
[3]
Wei Liang
journal
Translational cancer research
year
2023
abstract
Background: The extracellular matrix (ECM) plays a vital role in progression, expansion, and prognosis of malignancies. In this study, we aimed to explore a novel ECM-based prognostic model for patients with colon cancer (CC). Methods: ECM-related genes were obtained from Molecular Signatures database. Differential expression analysis was performed using the CC dataset from The Cancer Genome Atlas (TCGA) database. Four ECM-related genes related to overall survival were identified using the Cox regression and LASSO analysis. Then an ECM-related signature was developed and verified in three independent CC cohorts (GSE33882, GSE39582 and GSE29621) from the Gene Expression Omnibus (GEO). A prognostic nomogram was developed incorporating the ECM-related gene signature with clinical risk factors. CIBERSORT was used to explore the immune cell infiltration level. Human Protein Atlas (HPA) database was utilized to validate the expression levels of identified prognostic ECM genes. Results: Four ECM-related genes (CXCL13, CXCL14, SFRP5 and THBS4) were identified to develop an ECM-based gene signature and demarcated CC patients into the high- and low-risk groups. In training and validation datasets, patients in the low-risk group had better overall survival outcomes than those in the high-risk group (log-rank P<0.001). In addition, ECM-related signature was significantly associated with consensus molecular subtype 4 (CMS4) as well as other known clinical risk factors such as a higher Tumor, Nodal Involvement, Metastasis (TNM) stage. Moreover, the risk score derived from the ECM-based gene signature could be utilized as an independent prognostic factor for CC patients. A nomogram including the ECM-related gene signature, age and stage was developed to serve clinical practice. CIBERSORT analysis showed immune cell infiltration was different between high- and low-risk groups. The immunohistochemical results derived from HPA indicated differential expression of prognosis-related ECM genes in CC and normal tissues. Conclusions: In the present study, a novel risk model based on ECM-signature could effectively reflect individual risk classification and provide potential therapeutic targets for CC patients. Moreover, the prognostic nomogram may help predict individualized survival.
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Four ECM-related genes related to overall survival were identified using the Cox regression and LASSO analysis.
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Data Sharing Statement: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2036/dss
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In training and validation datasets, patients in the low-risk group had better overall survival outcomes than those in the high-risk group (log-rank P<0.001).
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In training and validation datasets, patients in the low-risk group had better overall survival outcomes than those in the high-risk group (log-rank P<0.001).
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[186]
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[187]
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[188]
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[194]
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[197]
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[198]
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[199]
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[200]
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[201]
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[202]
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[203]
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[204]
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[205]
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[206]
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[207]
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[208]
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[209]
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[210]
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[211]
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[212]
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[213]
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[214]
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[215]
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[216]
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[217]
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[218]
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[219]
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[220]
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[221]
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[222]
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[223]
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[224]
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[225]
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[226]
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[227]
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[228]
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[229]
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[230]
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[231]
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[232]
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[233]
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[234]
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[235]
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[236]
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[237]
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[238]
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[239]
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[240]
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[241]
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[242]
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[243]
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[244]
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[245]
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[246]
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[247]
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[249]
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[250]
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[251]
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[252]
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[253]
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[254]
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[255]
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[256]
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[257]
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[258]
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[259]
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[260]
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[261]
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[262]
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[263]
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[264]
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[265]
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[266]
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[267]
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[268]
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[269]
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[270]
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[271]
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[272]
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[273]
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[274]
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[275]
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[276]
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[280]
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[281]
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[285]
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[286]
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[287]
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[288]
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[289]
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[290]
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[291]
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[293]
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[294]
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[296]
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[297]
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[298]
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[299]
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[300]
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[301]
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[302]
GSM972240
[303]
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[304]
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[305]
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[306]
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[307]
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[308]
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[309]
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[310]
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[311]
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[312]
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[313]
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[314]
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[315]
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[316]
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[317]
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[318]
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[319]
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[320]
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[321]
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[322]
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[323]
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[324]
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[325]
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[326]
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[327]
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[328]
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[329]
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[330]
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[331]
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[332]
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[333]
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[334]
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[335]
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[336]
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[337]
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[338]
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[339]
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[340]
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[341]
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[342]
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[343]
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[344]
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[345]
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[346]
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[347]
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[348]
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[349]
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[350]
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[351]
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[352]
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[353]
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[354]
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[355]
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[356]
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[357]
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[358]
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[359]
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[360]
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[361]
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[362]
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[363]
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[364]
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[365]
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[366]
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[367]
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[368]
GSM972306
[369]
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[370]
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[371]
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[372]
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[373]
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[374]
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[375]
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[376]
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[377]
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[378]
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[379]
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[380]
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[381]
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[382]
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[383]
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[384]
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[385]
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[386]
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[387]
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[388]
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[389]
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[390]
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[391]
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[392]
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[393]
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[394]
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[395]
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[396]
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[397]
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[398]
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[399]
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[400]
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[401]
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[402]
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[403]
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[404]
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[405]
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[406]
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[407]
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[408]
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[409]
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[410]
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[411]
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[412]
GSM972350
[413]
GSM972351
[414]
GSM972352
[415]
GSM972353
[416]
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[417]
GSM972355
[418]
GSM972356
[419]
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[420]
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[421]
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[422]
GSM972360
[423]
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[424]
GSM972362
[425]
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[426]
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[427]
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[428]
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[429]
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[430]
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[431]
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[432]
GSM972370
[433]
GSM972371
[434]
GSM972372
[435]
GSM972373
[436]
GSM972374
[437]
GSM972375
[438]
GSM972376
[439]
GSM972377
[440]
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[441]
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[442]
GSM972380
[443]
GSM972381
[444]
GSM972382
[445]
GSM972383
[446]
GSM972384
[447]
GSM972385
[448]
GSM972386
[449]
GSM972387
[450]
GSM972388
[451]
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[452]
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[453]
GSM972391
[454]
GSM972392
[455]
GSM972393
[456]
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[457]
GSM972395
[458]
GSM972396
[459]
GSM972397
[460]
GSM972398
[461]
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[462]
GSM972400
[463]
GSM972401
[464]
GSM972402
[465]
GSM972403
[466]
GSM972404
[467]
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[468]
GSM972406
[469]
GSM972407
[470]
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[471]
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[472]
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[473]
GSM972411
[474]
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[475]
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[476]
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[477]
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[478]
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[479]
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[480]
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[481]
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[482]
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[483]
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[484]
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[485]
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[486]
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[487]
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[488]
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[489]
GSM972427
[490]
GSM972428
[491]
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[492]
GSM972430
[493]
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[494]
GSM972432
[495]
GSM972433
[496]
GSM972434
[497]
GSM972435
[498]
GSM972436
[499]
GSM972437
[500]
GSM972438
[501]
GSM972439
[502]
GSM972440
[503]
GSM972441
[504]
GSM972442
[505]
GSM972443
[506]
GSM972444
[507]
GSM972445
[508]
GSM972446
[509]
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[510]
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[511]
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[512]
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[513]
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[514]
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[515]
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[516]
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[517]
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[518]
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[519]
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[520]
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[521]
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[522]
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[523]
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[524]
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[525]
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[526]
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[527]
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[528]
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[529]
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[530]
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[531]
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[532]
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[533]
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[534]
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[535]
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[536]
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[537]
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[538]
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[539]
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[540]
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[541]
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[542]
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[543]
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[544]
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[545]
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[546]
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[547]
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[548]
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[549]
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[550]
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[551]
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[552]
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[553]
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[554]
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[555]
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[556]
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[557]
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[558]
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[560]
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[561]
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[562]
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[563]
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[564]
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[565]
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[566]
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[567]
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[568]
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[569]
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[570]
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[571]
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[572]
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[573]
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[574]
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[575]
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[576]
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[577]
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[578]
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[579]
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[580]
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[581]
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[582]
GSM972520
[583]
GSM972521
[584]
GSM972522
sample_count
585
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Gene expression Classification of Colon Cancer defines six molecular subtypes with distinct clinical, molecular and survival characteristics [Expression]
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 8 items
[0]
asset:data:geo:GSE29621 not downloaded
[1]
asset:data:geo:GSE29621 licence not read
[2]
asset:data:geo:GSE33882 not downloaded
[3]
asset:data:geo:GSE33882 licence not read
[4]
asset:data:geo:GSE38832 not downloaded
[5]
asset:data:geo:GSE38832 licence not read
[6]
asset:data:geo:GSE39582 not downloaded
[7]
asset:data:geo:GSE39582 licence not read
analysis object · 4 fields
state
complete
methods array · 3 items
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
1
band
verbatim
quote
Four ECM-related genes related to overall survival were identified using the Cox regression and LASSO analysis.
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
dsl_operations array · 1 item
[0]
survival_km
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
quote
Kaplan-Meier
[2] object · 10 fields
id
method-3
family
survival_analysis
specific
log_rank_test
label
Survival analysis
dsl_operations array · 1 item
[0]
logrank_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.7
band
medium
quote
log-rank
targets array · 1 item
[0] object · 8 fields
id
target-published-estimate
claim_id
claim-target-result
operation
cox_ph
unit
p-value
tolerance
null
state
complete
note
The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold.
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 4 items
[0]
GSE33882
[1]
GSE38832
[2]
GSE39582
[3]
GSE29621
resolved_accessions array · 4 items
[0]
GSE33882
[1]
GSE38832
[2]
GSE39582
[3]
GSE29621
statements array · 1 item
[0]
Data Sharing Statement: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2036/dss
basis
The paper names GSE33882, GSE38832, GSE39582, GSE29621 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
cox_ph
assets array · 2 items
[0]
source:pmid:36915600
[1]
data:geo:GSE29621
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE29621
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-11-01T18:33:33Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
15247
completion_tokens
2123
cached_tokens
0
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
runs array · 0 items
gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:36915600
type
paper
label
pmid:36915600
[1] object · 3 fields
id
source:pmid:36915600
type
manuscript
label
PMID 36915600 full text
[2] object · 3 fields
id
data:geo:GSE29621
type
dataset
label
GEO GSE29621
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:36915600
type
paper
label
pmid:36915600
[1] object · 3 fields
id
source:pmid:36915600
type
manuscript
label
PMID 36915600 full text
[2] object · 3 fields
id
data:geo:GSE29621
type
dataset
label
GEO GSE29621
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-36915600
type
extraction
used array · 1 item
[0]
source:pmid:36915600
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE29621
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE29621
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
type
software
label
MiniMax literature reader
source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:36915600
parent_hash
sha256:79f6aaaa1e706751d3f514f44aeb31ac46d7d144100f2f299fbe372097babeca
fork_of
null
gaps array · 12 items
[0]
asset:data:geo:GSE29621 licence not read
[1]
asset:data:geo:GSE29621 not downloaded
[2]
asset:data:geo:GSE33882 licence not read
[3]
asset:data:geo:GSE33882 not downloaded
[4]
asset:data:geo:GSE38832 licence not read
[5]
asset:data:geo:GSE38832 not downloaded
[6]
asset:data:geo:GSE39582 licence not read
[7]
asset:data:geo:GSE39582 not downloaded
[8]
execution.not_run
[9]
review.human_critique
[10]
review.independent_reader
[11]
review.machine_critique
assays array · 2 items
[0] object · 11 fields
role
data_generation
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.93
evidence array · 1 item
[0]
erent between high- and low-risk groups. The immunohistochemical results derived from HPA indicated different
order_basis
paper_text_order:1965
id
assay:1
[1] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
cox_ph
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Four ECM-related genes related to overall survival were identified using the Cox regression and LASSO analysis.
order_basis
consumes_earlier_output
id
assay:2
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36915600", "kind": "science-record", "revision": 2, "content_hash": "sha256:9d8291b55e9e9bb8cd0768fcb35b4967a6fc975529967f7c4bdb8e29ad859d83", "created_at": "2026-11-01T19:01:33Z", "updated_at": "2026-11-01T21:30:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Extracellular matrix-based gene signature for predicting prognosis in colon cancer and immune microenvironment.", "doi": "10.21037/tcr-22-2036", "pmid": "36915600", "authors": ["Ruoyang Chai", "Zhengjia Su", "Yajie Zhao", "Wei Liang"], "journal": "Translational cancer research", "year": 2023, "abstract": "Background: The extracellular matrix (ECM) plays a vital role in progression, expansion, and prognosis of malignancies. In this study, we aimed to explore a novel ECM-based prognostic model for patients with colon cancer (CC).\nMethods: ECM-related genes were obtained from Molecular Signatures database. Differential expression analysis was performed using the CC dataset from The Cancer Genome Atlas (TCGA) database. Four ECM-related genes related to overall survival were identified using the Cox regression and LASSO analysis. Then an ECM-related signature was developed and verified in three independent CC cohorts (GSE33882, GSE39582 and GSE29621) from the Gene Expression Omnibus (GEO). A prognostic nomogram was developed incorporating the ECM-related gene signature with clinical risk factors. CIBERSORT was used to explore the immune cell infiltration level. Human Protein Atlas (HPA) database was utilized to validate the expression levels of identified prognostic ECM genes.\nResults: Four ECM-related genes (CXCL13, CXCL14, SFRP5 and THBS4) were identified to develop an ECM-based gene signature and demarcated CC patients into the high- and low-risk groups. In training and validation datasets, patients in the low-risk group had better overall survival outcomes than those in the high-risk group (log-rank P<0.001). In addition, ECM-related signature was significantly associated with consensus molecular subtype 4 (CMS4) as well as other known clinical risk factors such as a higher Tumor, Nodal Involvement, Metastasis (TNM) stage. Moreover, the risk score derived from the ECM-based gene signature could be utilized as an independent prognostic factor for CC patients. A nomogram including the ECM-related gene signature, age and stage was developed to serve clinical practice. CIBERSORT analysis showed immune cell infiltration was different between high- and low-risk groups. The immunohistochemical results derived from HPA indicated differential expression of prognosis-related ECM genes in CC and normal tissues.\nConclusions: In the present study, a novel risk model based on ECM-signature could effectively reflect individual risk classification and provide potential therapeutic targets for CC patients. Moreover, the prognostic nomogram may help predict individualized survival.", "claims": [{"id": "claim-method", "statement": "Four ECM-related genes related to overall survival were identified using the Cox regression and LASSO analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36915600", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Four ECM-related genes related to overall survival were identified using the Cox regression and LASSO analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Sharing Statement: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2036/dss", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36915600", "locator": "sections[26] \"Footnotes\" paragraph 2", "quote": "Data Sharing Statement: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2036/dss"}], "state": "complete"}, {"id": "claim-target-result", "statement": "In training and validation datasets, patients in the low-risk group had better overall survival outcomes than those in the high-risk group (log-rank P<0.001).", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "In training and validation datasets, patients in the low-risk group had better overall survival outcomes than those in the high-risk group (log-rank P<0.001)."}, "evidence": [{"asset": "source:pmid:36915600", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In training and validation datasets, patients in the low-risk group had better overall survival outcomes than those in the high-risk group (log-rank P<0.001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In training and validation datasets, patients in the low-risk group had better overall survival outcomes than those in the high-risk group (log-rank P<0.001).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36915600"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE29621"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE29621"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36915600", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/tcr-22-2036", "sha256": 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