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pmid:38313020

A ubiquitination-related risk model for predicting the prognosis and immunotherapy response of gastric adenocarcinoma patients.

Shuai Shao · Yang Sun · Dongmei Zhao · Yu Tian · Yifan Yang · Nan Luo

PeerJ · 2024 doi:10.7717/peerj.16868

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A ubiquitination-related risk model for predicting the prognosis and immunotherapy response of gastric adenocarcinoma patients.
doi
10.7717/peerj.16868
pmid
38313020
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Shuai Shao
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Yang Sun
[2]
Dongmei Zhao
[3]
Yu Tian
[4]
Yifan Yang
[5]
Nan Luo
journal
PeerJ
year
2024
abstract
Ubiquitination is crucial for the growth of cancer. However, the role of ubiquitination-related genes (URGs) in stomach adenocarcinoma (STAD) remains unclear. Differentially expressed URGs (DE-URGs) were examined in the whole TCGA-STAD dataset, and the prognosis-related genes were discovered from the The Cancer Genome Atlas (TCGA) training set. Prognostic genes were discovered using selection operator regression analysis and absolute least shrinkage (LASSO). A multivariate Cox analysis was further employed, and a polygene-based risk assessment system was established. Signatures were verified using the Gene Expression Omnibus (GEO) database record GSE84433 and the TCGA test set. Using the MEXPRESS dataset, a detailed analysis of gene expression and methylation was carried out. Using the DAVID database, DE-URG function and pathway enrichment was examined. The identified 163 DE-URGs were significantly associated with pathways related to protein ubiquitination, cell cycle, and cancer. A prognostic signature based on 13 DE-URGs was constructed, classifying patients into two risk groups. Compared to low-risk patients, people at high risk had considerably shorter survival times. Cox regression analyses considered prognostic parameters independent of age and risk score and were used to generate nomograms. Calibration curves show good agreement between nomogram predictions and observations. Furthermore, the results of the MEXPRESS analysis indicated that 13 prognostic DE-URGs had an intricate methylation profile. The enhanced Random Forest-based model showed greater efficacy in predicting prognosis, mutation, and immune infiltration. The in vitro validation, including CCK8, EdU, Transwell, and co-culture Transwell, proved that RNF144A was a potent oncogene in STAD and could facilitate the migration of M2 macrophages. In this research, we have created a genetic model based on URGs that can appropriately gauge a patient's prognosis and immunotherapy response, providing clinicians with a reliable tool for prognostic assessment and supporting clinical treatment decisions.
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LASSO regression analysis also included genes connected to the above prognosis to predict STAD prognosis.
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sections[6] "Selection of prognosis-related genes" paragraph 2
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LASSO regression analysis also included genes connected to the above prognosis to predict STAD prognosis.
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The following information was supplied regarding data availability:The raw measurements, R codes, matrices and the raw data of the in vitro validation are available in the Supplementary Files.
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The risk scoring system’s AUCs for projecting STAD patients’ 1-, 3-, and 5-year OS in the TCGA training group were, respectively, 0.665, 0.618, and 0.722, according to the ROC curve (Fig. 1F).
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sections[17] "Establishment and evaluation of the 13 DE-URGs-based prognostic signatures in the TCGA-training set" paragraph 2
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The risk scoring system’s AUCs for projecting STAD patients’ 1-, 3-, and 5-year OS in the TCGA training group were, respectively, 0.665, 0.618, and 0.722, according to the ROC curve (Fig. 1F).
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The risk scoring system’s AUCs for projecting STAD patients’ 1-, 3-, and 5-year OS in the TCGA training group were, respectively, 0.665, 0.618, and 0.722, according to the ROC curve (Fig. 1F).
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[55]
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[56]
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[63]
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[64]
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[65]
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[66]
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[67]
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[68]
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[69]
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[70]
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[71]
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[72]
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[73]
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[74]
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[75]
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[76]
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[77]
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[78]
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[79]
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[80]
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[83]
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[84]
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[85]
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[86]
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[87]
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[88]
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[97]
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[98]
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[99]
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[100]
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[108]
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[118]
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[119]
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[120]
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[121]
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[125]
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[126]
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[128]
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[129]
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[130]
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[131]
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[132]
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[133]
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[134]
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[135]
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[136]
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[137]
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[138]
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[139]
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[140]
GSM2235840
[141]
GSM2235841
[142]
GSM2235842
[143]
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[144]
GSM2235844
[145]
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[146]
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[147]
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[148]
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[149]
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[150]
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[151]
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[152]
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[153]
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[154]
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[155]
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[156]
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[157]
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[158]
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[159]
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[160]
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[161]
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[162]
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[163]
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[164]
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[165]
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[166]
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[167]
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[168]
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[169]
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[170]
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[171]
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[172]
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[173]
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[174]
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[175]
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[176]
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[177]
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[178]
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[179]
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[180]
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[181]
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[182]
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[183]
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[184]
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[185]
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[186]
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[187]
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[188]
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[189]
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[190]
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[191]
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[192]
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[193]
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[194]
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[195]
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[196]
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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]
GSM2235940
[206]
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[207]
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[208]
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[209]
GSM2235944
[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]
GSM2235951
[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]
GSM2235962
[228]
GSM2235963
[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]
GSM2235969
[235]
GSM2235970
[236]
GSM2235971
[237]
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[238]
GSM2235973
[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]
GSM2235979
[245]
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[246]
GSM2235981
[247]
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[248]
GSM2235983
[249]
GSM2235984
[250]
GSM2235985
[251]
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[252]
GSM2235987
[253]
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[254]
GSM2235991
[255]
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[256]
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[257]
GSM2235994
[258]
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[259]
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[260]
GSM2235997
[261]
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[262]
GSM2235999
[263]
GSM2236000
[264]
GSM2236001
[265]
GSM2236002
[266]
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[267]
GSM2236004
[268]
GSM2236005
[269]
GSM2236006
[270]
GSM2236007
[271]
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[272]
GSM2236009
[273]
GSM2236010
[274]
GSM2236011
[275]
GSM2236012
[276]
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[277]
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[278]
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[279]
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[280]
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[281]
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[282]
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[283]
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[284]
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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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[292]
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[293]
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[294]
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[295]
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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]
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[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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[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]
GSM2236084
[346]
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[347]
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[348]
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[349]
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[350]
GSM2236089
[351]
GSM2236090
[352]
GSM2236091
[353]
GSM2236092
[354]
GSM2236093
[355]
GSM2236094
[356]
GSM2236095
sample_count
357
group_sizes
null
group_sizes_basis
null
platform
6947
taxon
Homo sapiens
title
Molecular subtypes in gastric cancer. [II]
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 10 items
[0]
asset:data:geo:GSE13911 not downloaded
[1]
asset:data:geo:GSE13911 licence not read
[2]
asset:data:geo:GSE19826 not downloaded
[3]
asset:data:geo:GSE19826 licence not read
[4]
asset:data:geo:GSE54129 not downloaded
[5]
asset:data:geo:GSE54129 licence not read
[6]
asset:data:geo:GSE65801 not downloaded
[7]
asset:data:geo:GSE65801 licence not read
[8]
asset:data:geo:GSE84433 not downloaded
[9]
asset:data:geo:GSE84433 licence not read
analysis object · 4 fields
state
partial
methods array · 8 items
[0] object · 10 fields
id
method-1
family
group_comparison
specific
anova
label
Group comparison
dsl_operations array · 4 items
[0]
group_summary
[1]
welch_t
[2]
bootstrap_mean_difference
[3]
group_comparison_anova
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
band
high
quote
analysis of variance
[1] object · 10 fields
id
method-2
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
0.7
band
medium
quote
Cox regression
[2] object · 10 fields
id
method-3
family
differential_expression
specific
limma_voom
label
Differential expression analysis
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
0.8
band
high
quote
limma
[3] object · 10 fields
id
method-4
family
machine_learning
specific
random_forest
label
Machine learning
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
machine_learning_random_forest
expressible
false
parameters object · 0 fields
data_shapes array · 1 item
[0]
labelled_feature_matrix
evidence object · 3 fields
score
0.7
band
medium
quote
Random Forest
[4] object · 10 fields
id
method-5
family
correlation_analysis
specific
pearson
label
Correlation analysis
dsl_operations array · 1 item
[0]
pearson_r
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
paired_numeric_columns
evidence object · 3 fields
score
0.8
band
high
quote
Pearson correlation
[5] object · 10 fields
id
method-6
family
network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
pathway enrichment
[6] object · 10 fields
id
method-7
family
contingency_analysis
specific
chi_square
label
Categorical (contingency table) analysis
dsl_operations array · 1 item
[0]
chi_square_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
categorical_cross_tabulation
evidence object · 3 fields
score
0.8
band
high
quote
Chi-square
[7] object · 10 fields
id
method-8
family
null
specific
null
label
LASSO regression analysis
dsl_operations array · 0 items
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 0 items
evidence object · 3 fields
score
1
band
verbatim
quote
LASSO regression analysis also included genes connected to the above prognosis to predict STAD prognosis.
targets array · 0 items
gaps array · 1 item
[0]
method.reader_named_unmapped
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 · 4 items
[0]
group_summary
[1]
welch_t
[2]
bootstrap_mean_difference
[3]
group_comparison_anova
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: anova.
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 · 5 items
[0]
GSE84433
[1]
GSE13911
[2]
GSE19826
[3]
GSE54129
[4]
GSE65801
resolved_accessions array · 5 items
[0]
GSE84433
[1]
GSE13911
[2]
GSE19826
[3]
GSE54129
[4]
GSE65801
statements array · 1 item
[0]
The following information was supplied regarding data availability:The raw measurements, R codes, matrices and the raw data of the in vitro validation are available in the Supplementary Files.
basis
The paper names GSE84433, GSE13911, GSE19826, GSE54129, GSE65801 in 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 · 4 items
[0]
group_summary
[1]
welch_t
[2]
bootstrap_mean_difference
[3]
group_comparison_anova
assets array · 2 items
[0]
source:pmid:38313020
[1]
data:geo:GSE13911
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:GSE13911
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
2026-11-01T19:07:54Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
18483
completion_tokens
3546
cached_tokens
128
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:38313020
type
paper
label
pmid:38313020
[1] object · 3 fields
id
source:pmid:38313020
type
manuscript
label
PMID 38313020 full text
[2] object · 3 fields
id
data:geo:GSE13911
type
dataset
label
GEO GSE13911
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:38313020
type
paper
label
pmid:38313020
[1] object · 3 fields
id
source:pmid:38313020
type
manuscript
label
PMID 38313020 full text
[2] object · 3 fields
id
data:geo:GSE13911
type
dataset
label
GEO GSE13911
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-38313020
type
extraction
used array · 1 item
[0]
source:pmid:38313020
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE13911
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE13911
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:38313020
parent_hash
sha256:3ed784126f94e15d2257b14a2babc7282ee44ead744c652e391834b5c832bda9
fork_of
null
gaps array · 15 items
[0]
asset:data:geo:GSE13911 licence not read
[1]
asset:data:geo:GSE13911 not downloaded
[2]
asset:data:geo:GSE19826 licence not read
[3]
asset:data:geo:GSE19826 not downloaded
[4]
asset:data:geo:GSE54129 licence not read
[5]
asset:data:geo:GSE54129 not downloaded
[6]
asset:data:geo:GSE65801 licence not read
[7]
asset:data:geo:GSE65801 not downloaded
[8]
asset:data:geo:GSE84433 licence not read
[9]
asset:data:geo:GSE84433 not downloaded
[10]
execution.not_run
[11]
method.reader_named_unmapped
[12]
review.human_critique
[13]
review.independent_reader
[14]
review.machine_critique
assays array · 3 items
[0] object · 11 fields
role
data_generation
definition_id
apoptosis_assay
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 3 items
[0]
ltration. The in vitro validation, including CCK8, EdU, Transwell, and co-culture Transwell, p
[1]
l results were based on student t-tests. (B) CCK-8 results of the OD values in three groups (NC
[2]
B, in MKN-7, the OD values obtained from the CCK-8 test were significantly decreased in the si-
order_basis
paper_text_order:1771
id
assay:1
[1] object · 11 fields
role
data_generation
definition_id
rna_seq
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]
nalysis of the STAD-related DE-URGs Based on RNA-Seq data from STAD (n = 375) and normal samples
order_basis
paper_text_order:3124
id
assay:2
[2] object · 11 fields
role
analysis
definition_id
group_comparison
definition_version
f2132e96ae6c7a4e
required_operations array · 4 items
[0]
group_summary
[1]
welch_t
[2]
bootstrap_mean_difference
[3]
group_comparison_anova
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
analysis of variance
order_basis
consumes_earlier_output
id
assay:3
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38313020", "kind": "science-record", "revision": 3, "content_hash": "sha256:85e784924d7915d0e85aae2a978a3d7a05438a7dfb30815a9058892c9054bf81", "created_at": "2026-11-01T19:20:15Z", "updated_at": "2026-11-01T22:11:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A ubiquitination-related risk model for predicting the prognosis and immunotherapy response of gastric adenocarcinoma patients.", "doi": "10.7717/peerj.16868", "pmid": "38313020", "authors": ["Shuai Shao", "Yang Sun", "Dongmei Zhao", "Yu Tian", "Yifan Yang", "Nan Luo"], "journal": "PeerJ", "year": 2024, "abstract": "Ubiquitination is crucial for the growth of cancer. However, the role of ubiquitination-related genes (URGs) in stomach adenocarcinoma (STAD) remains unclear. Differentially expressed URGs (DE-URGs) were examined in the whole TCGA-STAD dataset, and the prognosis-related genes were discovered from the The Cancer Genome Atlas (TCGA) training set. Prognostic genes were discovered using selection operator regression analysis and absolute least shrinkage (LASSO). A multivariate Cox analysis was further employed, and a polygene-based risk assessment system was established. Signatures were verified using the Gene Expression Omnibus (GEO) database record GSE84433 and the TCGA test set. Using the MEXPRESS dataset, a detailed analysis of gene expression and methylation was carried out. Using the DAVID database, DE-URG function and pathway enrichment was examined. The identified 163 DE-URGs were significantly associated with pathways related to protein ubiquitination, cell cycle, and cancer. A prognostic signature based on 13 DE-URGs was constructed, classifying patients into two risk groups. Compared to low-risk patients, people at high risk had considerably shorter survival times. Cox regression analyses considered prognostic parameters independent of age and risk score and were used to generate nomograms. Calibration curves show good agreement between nomogram predictions and observations. Furthermore, the results of the MEXPRESS analysis indicated that 13 prognostic DE-URGs had an intricate methylation profile. The enhanced Random Forest-based model showed greater efficacy in predicting prognosis, mutation, and immune infiltration. The in vitro validation, including CCK8, EdU, Transwell, and co-culture Transwell, proved that RNF144A was a potent oncogene in STAD and could facilitate the migration of M2 macrophages. In this research, we have created a genetic model based on URGs that can appropriately gauge a patient's prognosis and immunotherapy response, providing clinicians with a reliable tool for prognostic assessment and supporting clinical treatment decisions.", "claims": [{"id": "claim-method", "statement": "LASSO regression analysis also included genes connected to the above prognosis to predict STAD prognosis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38313020", "locator": "sections[6] \"Selection of prognosis-related genes\" paragraph 2", "quote": "LASSO regression analysis also included genes connected to the above prognosis to predict STAD prognosis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:The raw measurements, R codes, matrices and the raw data of the in vitro validation are available in the Supplementary Files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38313020", "locator": "sections[35] \"Data Availability\" paragraph 2", "quote": "The following information was supplied regarding data availability:The raw measurements, R codes, matrices and the raw data of the in vitro validation are available in the Supplementary Files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The risk scoring system’s AUCs for projecting STAD patients’ 1-, 3-, and 5-year OS in the TCGA training group were, respectively, 0.665, 0.618, and 0.722, according to the ROC curve (Fig. 1F).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38313020", "locator": "sections[17] \"Establishment and evaluation of the 13 DE-URGs-based prognostic signatures in the TCGA-training set\" paragraph 2", "quote": "The risk scoring system’s AUCs for projecting STAD patients’ 1-, 3-, and 5-year OS in the TCGA training group were, respectively, 0.665, 0.618, and 0.722, according to the ROC curve (Fig. 1F)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The risk scoring system’s AUCs for projecting STAD patients’ 1-, 3-, and 5-year OS in the TCGA training group were, respectively, 0.665, 0.618, and 0.722, according to the ROC curve (Fig. 1F).", "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:38313020"], "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:GSE13911"], "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:GSE13911"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38313020", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.16868", "sha256": 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