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pmid:39115879
Exploration of bacterial lipopolysaccharide-related genes signature based on T cells for predicting prognosis in colorectal cancer.
Lichao Cao · Ying Ba · Fang Chen · Shenrui Zhang · Hezi Zhang
Aging · 2024 doi:10.18632/aging.206041
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Experiment
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Complete file
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Therefore, we conducted a systematic analysis of relationship between bacterial lipopolysaccharide (LPS)-associated genes and immune cells to explore new biomarkers for predicting the prognosis of CRC.\nMETHODS: The single-cell RNA sequencing data and the Comparative Toxicogenomics Database were used to screen T cells-associated LPS-related genes (TALRGs). Then, we established and validated the TALRGs risk signature in The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) cohort and GSE39582 cohort. Besides, we compared the differences in tumor-infiltrating immune cell types, immunotherapeutic response, somatic mutation profiles, and tumor mutation burden (TMB) between high-risk group and low-risk group. In addition, the immunotherapeutic cohort (Imvigor210) treated with an anti-PD-L1 agent was performed to explore the potential value of the TALRGs signature on immunotherapy.\nRESULTS: Five prognostic TALRGs were identified and selected to build the prognostic model. The high-risk group had poor prognosis in both TCGA-COAD cohort (P < 0.0001) and GSE39582 cohort (P = 0.00019). The areas under the curves (AUCs) of TALRGs signature were calculated (TCGA-COAD cohort: 0.624 at 1 years, 0.639 at 3 years, 0.648 at 5 years; anti-PD-L1 cohort was 0.59). The high-risk group had advanced pathological stages and higher TMN stages in both TCGA-COAD cohort and GSE39582 cohort. The high-risk group had the higher infiltration of immunosuppressive cells, the expressions of immune checkpoint molecules, the IC50 values of chemotherapy drugs, and TP53 mutation rate (P < 0.05). In addition, patients with high TMB had worse prognosis (P < 0.05). Furthermore, the Imvigor210 also showed patients with high-risk scores had poor prognosis (platinum-treated cohort: P = 0.0032; non-platinum-treated cohort: P = 0.00017).\nCONCLUSIONS: Microorganisms are closely related to the tumor microenvironment to influence the progression and immune response of CRC via stimulating T cells through LPS-related genes. The TALRGs signature contributed to predict the prognosis and immunotherapy of CRC, and became new therapeutic targets and biomarkers of CRC.", "claims": [{"id": "claim-method", "statement": "Univariate Cox analysis was used to screen the prognostic signature using Survival R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39115879", "locator": "sections[5] \"Development and validation of the TALRGs prognostic model\" paragraph 2", "quote": "Univariate Cox analysis was used to screen the prognostic signature using Survival R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The scRNA-seq dataset GSE200997 was obtained from the Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov) database, which included 16 CRC samples and 7 adjacent samples of normal colon tissue.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39115879", "locator": "sections[3] \"Acquisition and processing of data\" paragraph 2", "quote": "The scRNA-seq dataset GSE200997 was obtained from the Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov) database, which included 16 CRC samples and 7 adjacent samples of normal colon tissue."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Five prognostic TALRGs were identified and selected to build the prognostic model.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39115879", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Five prognostic TALRGs were identified and selected to build the prognostic model."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Five prognostic TALRGs were identified and selected to build the prognostic model.", "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:39115879"], "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:GSE200997"], "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:GSE200997"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39115879", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.18632/aging.206041", "sha256": 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