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pmid:38042786

Discovery of a novel lipid metabolism-related gene signature to predict outcomes and the tumor immune microenvironment in gastric cancer by integrated analysis of single-cell and bulk RNA sequencing.

Jinze Zhang · He Wang · Yu Tian · Tianfeng Li · Wei Zhang · Li Ma · Xiangjuan Chen · Yushan Wei

Lipids in health and disease · 2023 doi:10.1186/s12944-023-01977-y

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Discovery of a novel lipid metabolism-related gene signature to predict outcomes and the tumor immune microenvironment in gastric cancer by integrated analysis of single-cell and bulk RNA sequencing.
doi
10.1186/s12944-023-01977-y
pmid
38042786
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Jinze Zhang
[1]
He Wang
[2]
Yu Tian
[3]
Tianfeng Li
[4]
Wei Zhang
[5]
Li Ma
[6]
Xiangjuan Chen
[7]
Yushan Wei
journal
Lipids in health and disease
year
2023
abstract
Gastric cancer (GC) is a pressing global clinical issue, with few treatment options and a poor prognosis. The onset and spread of stomach cancer are significantly influenced by changes in lipid metabolism-related pathways. This study aimed to discover a predictive signature for GC using lipid metabolism-related genes (LMRGs) and examine its correlation with the tumor immune microenvironment (TIME). Transcriptome data and clinical information from patients with GC were collected from the TCGA and GEO databases. Data from GC samples were analyzed using both bulk RNA-seq and single-cell sequencing of RNA (scRNA-seq). To identify survival-related differentially expressed LMRGs (DE-LMRGs), differential expression and prognosis studies were carried out. We built a predictive signature using LASSO regression and tested it on the TCGA and GSE84437 datasets. In addition, the correlation of the prognostic signature with the TIME was comprehensively analyzed. In this study, we identified 258 DE-LMRGs in GC and further screened seven survival-related DE-LMRGs. The results of scRNA-seq identified 688 differentially expressed genes (DEGs) between the three branches. Two critical genes (GPX3 and NNMT) were identified using the above two gene groups. In addition, a predictive risk score that relies on GPX3 and NNMT was developed. Survival studies in both the TCGA and GEO datasets revealed that patients categorized to be at low danger had a significantly greater prognosis than those identified to be at high danger. Additionally, by employing calibration plots based on TCGA data, the study demonstrated the substantial predictive capacity of a prognostic nomogram, which incorporated a risk score along with various clinical factors. Within the high-risk group, there was a noticeable abundance of active natural killer (NK) cells, quiescent monocytes, macrophages, mast cells, and activated CD4 + T cells. In summary, a two-gene signature and a predictive nomogram have been developed, offering accurate prognostic predictions for general survival in GC patients. These findings have the potential to assist healthcare professionals in making informed medical decisions and providing personalized treatment approaches.
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A predictive gene signature was developed using a least absolute shrinkage and selection operator (LASSO) regression model, which helped to select optimal parameters and establish a sequence of genes with predictive capabilities.
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sections[6] "Creation and assessment of the LMRG signature" paragraph 2
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A predictive gene signature was developed using a least absolute shrinkage and selection operator (LASSO) regression model, which helped to select optimal parameters and establish a sequence of genes with predictive capabilities.
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The GPX3/NNMT-based two-gene prognostic signature achieved 1-, 3-, and 5-year overall-survival AUCs of 0.599, 0.610, and 0.640, respectively, while the prognostic nomogram achieved an AUC of 0.722.
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sections[15] "Construction and assessment of a prognostic model based on LMRGs" paragraph 2
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Figure 6K demonstrates the area under the curve (AUC) values for predicting OS at 1-year, 3-year, and 5-year intervals, which were measured to be 0.599, 0.610, and 0.640, respectively.
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sections[16] "Construction of a nomogram to forecast survival" paragraph 2
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Furthermore, the results of AUC testing demonstrated that the nomogram (AUC = 0.722) outperformed individual indicators such as age (AUC = 0.602), clinical stage (AUC = 0.617), and the predictive risk assessment model (AUC = 0.638) (Fig. 9C).
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The GPX3/NNMT-based two-gene prognostic signature achieved 1-, 3-, and 5-year overall-survival AUCs of 0.599, 0.610, and 0.640, respectively, while the prognostic nomogram achieved an AUC of 0.722.
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[90]
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[95]
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[97]
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[98]
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[99]
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[100]
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[101]
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[104]
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[105]
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[108]
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[109]
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[110]
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[113]
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[115]
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[116]
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[117]
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[118]
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[119]
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[120]
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[121]
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[122]
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[123]
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[124]
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[125]
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[127]
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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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[137]
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[138]
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[139]
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[140]
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[142]
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[143]
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[144]
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[150]
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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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[162]
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[163]
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[173]
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[174]
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[179]
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[218]
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[223]
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[224]
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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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[239]
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[240]
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[242]
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[243]
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[244]
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[246]
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[247]
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[248]
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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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[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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[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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[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]
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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]
GSM2236044
[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]
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[413]
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[414]
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[415]
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[416]
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[417]
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[418]
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[419]
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[420]
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[421]
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[422]
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[423]
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[424]
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[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]
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[433]
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[434]
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[435]
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[436]
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[437]
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[438]
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[439]
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[440]
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[441]
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[442]
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[443]
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[444]
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[445]
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[446]
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[447]
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[448]
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[449]
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[450]
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[451]
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[452]
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[453]
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[454]
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[455]
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[457]
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[458]
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[464]
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[465]
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[466]
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[467]
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[468]
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[471]
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[472]
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[473]
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[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]
GSM4419531
[481]
GSM4419532
[482]
GSM4419533
sample_count
483
group_sizes
null
group_sizes_basis
null
platform
6947
taxon
Homo sapiens
title
Molecular subtypes in gastric cancer.
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 · 6 items
[0]
asset:data:geo:GSE112302 not downloaded
[1]
asset:data:geo:GSE112302 licence not read
[2]
asset:data:geo:GSE62254 not downloaded
[3]
asset:data:geo:GSE62254 licence not read
[4]
asset:data:geo:GSE84437 not downloaded
[5]
asset:data:geo:GSE84437 licence not read
analysis object · 4 fields
state
partial
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
0.8
band
high
quote
Cox regression
[1] object · 10 fields
id
method-2
family
principal_component_analysis
specific
pca
label
Principal component analysis
dsl_operations array · 1 item
[0]
pca_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
wide_numeric_matrix
evidence object · 3 fields
score
0.8
band
high
quote
principal component analysis
[2] object · 10 fields
id
method-3
family
null
specific
null
label
Least absolute shrinkage and selection operator (LASSO) regression
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
A predictive gene signature was developed using a least absolute shrinkage and selection operator (LASSO) regression model, which helped to select optimal parameters and establish a sequence of genes with predictive capabilities.
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 · 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 · 3 items
[0]
GSE112302
[1]
GSE84437
[2]
GSE62254
resolved_accessions array · 3 items
[0]
GSE112302
[1]
GSE84437
[2]
GSE62254
statements array · 1 item
[0]
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
basis
The paper names GSE112302, GSE84437, GSE62254 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:38042786
[1]
data:geo:GSE112302
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:GSE112302
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
2026-11-01T19:01:31Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
15885
completion_tokens
2115
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:38042786
type
paper
label
pmid:38042786
[1] object · 3 fields
id
source:pmid:38042786
type
manuscript
label
PMID 38042786 full text
[2] object · 3 fields
id
data:geo:GSE112302
type
dataset
label
GEO GSE112302
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:38042786
type
paper
label
pmid:38042786
[1] object · 3 fields
id
source:pmid:38042786
type
manuscript
label
PMID 38042786 full text
[2] object · 3 fields
id
data:geo:GSE112302
type
dataset
label
GEO GSE112302
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-38042786
type
extraction
used array · 1 item
[0]
source:pmid:38042786
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE112302
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE112302
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:38042786
parent_hash
sha256:be9ec789f9fb1124cbdc8b0fa5465d24a2273bff0be73d315153e3d5d8769490
fork_of
null
gaps array · 11 items
[0]
asset:data:geo:GSE112302 licence not read
[1]
asset:data:geo:GSE112302 not downloaded
[2]
asset:data:geo:GSE62254 licence not read
[3]
asset:data:geo:GSE62254 not downloaded
[4]
asset:data:geo:GSE84437 licence not read
[5]
asset:data:geo:GSE84437 not downloaded
[6]
execution.not_run
[7]
method.reader_named_unmapped
[8]
review.human_critique
[9]
review.independent_reader
[10]
review.machine_critique
assays array · 3 items
[0] 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
0.99
evidence array · 3 items
[0]
integrated analysis of single-cell and bulk RNA sequencing.
[1]
rom GC samples were analyzed using both bulk RNA-seq and single-cell sequencing of RNA (scRNA-seq
[2]
th the tumor immune microenvironment (TIME). Transcriptome data and clinical information from patients
order_basis
paper_text_order:140
id
assay:1
[1] object · 11 fields
role
data_generation
definition_id
scrna_seq
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
unsupported
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 3 items
[0]
k RNA-seq and single-cell sequencing of RNA (scRNA-seq). To identify survival-related differentiall
[1]
en survival-related DE-LMRGs. The results of scRNA-seq identified 688 differentially expressed gene
[2]
Materials and methods Data processing of the scRNA-seq To preprocess and standardize the tumor spec
order_basis
paper_text_order:765
id
assay:2
[2] 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]
Cox regression
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:38042786", "kind": "science-record", "revision": 2, "content_hash": "sha256:938b2ef9067c9b8082924f57e1aefc0d105a8722056330e38e6e5180059e6a7c", "created_at": "2026-11-01T19:02:59Z", "updated_at": "2026-11-01T21:32:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Discovery of a novel lipid metabolism-related gene signature to predict outcomes and the tumor immune microenvironment in gastric cancer by integrated analysis of single-cell and bulk RNA sequencing.", "doi": "10.1186/s12944-023-01977-y", "pmid": "38042786", "authors": ["Jinze Zhang", "He Wang", "Yu Tian", "Tianfeng Li", "Wei Zhang", "Li Ma", "Xiangjuan Chen", "Yushan Wei"], "journal": "Lipids in health and disease", "year": 2023, "abstract": "Gastric cancer (GC) is a pressing global clinical issue, with few treatment options and a poor prognosis. The onset and spread of stomach cancer are significantly influenced by changes in lipid metabolism-related pathways. This study aimed to discover a predictive signature for GC using lipid metabolism-related genes (LMRGs) and examine its correlation with the tumor immune microenvironment (TIME). Transcriptome data and clinical information from patients with GC were collected from the TCGA and GEO databases. Data from GC samples were analyzed using both bulk RNA-seq and single-cell sequencing of RNA (scRNA-seq). To identify survival-related differentially expressed LMRGs (DE-LMRGs), differential expression and prognosis studies were carried out. We built a predictive signature using LASSO regression and tested it on the TCGA and GSE84437 datasets. In addition, the correlation of the prognostic signature with the TIME was comprehensively analyzed. In this study, we identified 258 DE-LMRGs in GC and further screened seven survival-related DE-LMRGs. The results of scRNA-seq identified 688 differentially expressed genes (DEGs) between the three branches. Two critical genes (GPX3 and NNMT) were identified using the above two gene groups. In addition, a predictive risk score that relies on GPX3 and NNMT was developed. Survival studies in both the TCGA and GEO datasets revealed that patients categorized to be at low danger had a significantly greater prognosis than those identified to be at high danger. Additionally, by employing calibration plots based on TCGA data, the study demonstrated the substantial predictive capacity of a prognostic nomogram, which incorporated a risk score along with various clinical factors. Within the high-risk group, there was a noticeable abundance of active natural killer (NK) cells, quiescent monocytes, macrophages, mast cells, and activated CD4 + T cells. In summary, a two-gene signature and a predictive nomogram have been developed, offering accurate prognostic predictions for general survival in GC patients. These findings have the potential to assist healthcare professionals in making informed medical decisions and providing personalized treatment approaches.", "claims": [{"id": "claim-method", "statement": "A predictive gene signature was developed using a least absolute shrinkage and selection operator (LASSO) regression model, which helped to select optimal parameters and establish a sequence of genes with predictive capabilities.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38042786", "locator": "sections[6] \"Creation and assessment of the LMRG signature\" paragraph 2", "quote": "A predictive gene signature was developed using a least absolute shrinkage and selection operator (LASSO) regression model, which helped to select optimal parameters and establish a sequence of genes with predictive capabilities."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38042786", "locator": "sections[24] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The GPX3/NNMT-based two-gene prognostic signature achieved 1-, 3-, and 5-year overall-survival AUCs of 0.599, 0.610, and 0.640, respectively, while the prognostic nomogram achieved an AUC of 0.722.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38042786", "locator": "sections[15] \"Construction and assessment of a prognostic model based on LMRGs\" paragraph 2", "quote": "Figure 6K demonstrates the area under the curve (AUC) values for predicting OS at 1-year, 3-year, and 5-year intervals, which were measured to be 0.599, 0.610, and 0.640, respectively."}, {"asset": "source:pmid:38042786", "locator": "sections[16] \"Construction of a nomogram to forecast survival\" paragraph 2", "quote": "Furthermore, the results of AUC testing demonstrated that the nomogram (AUC = 0.722) outperformed individual indicators such as age (AUC = 0.602), clinical stage (AUC = 0.617), and the predictive risk assessment model (AUC = 0.638) (Fig. 9C)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The GPX3/NNMT-based two-gene prognostic signature achieved 1-, 3-, and 5-year overall-survival AUCs of 0.599, 0.610, and 0.640, respectively, while the prognostic nomogram achieved an AUC of 0.722.", "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:38042786"], "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:GSE112302"], "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:GSE112302"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38042786", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12944-023-01977-y", "sha256": 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