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pmid:36950136
Multi-omics analysis reveals focal adhesion characteristic associated tumor immune microenvironment in colon adenocarcinoma.
Xiaoming Xu · Jingzhi Wang
Frontiers in genetics · 2023 doi:10.3389/fgene.2023.1088091
Paper
complete
Experiment
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Data
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Analysis
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Execution
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Complete file
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At the time of diagnosis, most of them have developed to the middle and late stages, and cancer cells have metastasized, and the prognosis is poor. Treatment options for progressive COAD are limited, and despite the promise of immunotherapy, immunotherapy response rates are low. The assembly and disaggregation of focal adhesion are critical for the directional migration of tumor cells to different sites, and it is unclear whether focal adhesion-related genes are involved in the development and prognosis of colon adenocarcinoma. This study aimed to investigate the role of focal adhesion genes in the occurrence and prognosis of COAD. We obtained datasets of COAD patients, including RNA-sequencing data and clinical information, from the TCGA and GEO databases (GSE17538 and GSE39582). Through CNMF clustering, two molecular subtypes with different expression patterns of focal adhesion genes were identified, and it was found that the molecular subtype with low expression of focal adhesion genes had better prognosis. Then the prediction signature was constructed by LASSO-Cox regression model, and the receiver operating characteristic (ROC) curve showed that the 4-gene signature had a good prediction effect on COAD 1-, 2-, and 3-year OS. Gene function enrichment analysis showed that the high-risk group was mainly enriched in immune and adhesion-related signaling pathways, suggesting that focal adhesion genes may affect the development and prognosis of COAD by regulating the immune microenvironment and tumor metastasis. The interaction between focal adhesion genes and immunity during the occurrence of COAD may help improve the response rate of immunotherapy, which also provides new ideas for the molecular mechanism and targeted therapy in COAD.", "claims": [{"id": "claim-method", "statement": "The 22 focal adhesion genes were further screened and collinearity was removed to obtain four focal adhesion genes, CAV2, FLT1, THBS3 and VAV3 through the LASSO-Cox algorithm (Figures 3A, B).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36950136", "locator": "sections[12] \"3.3 4-Genes signature is a robust prognostic factor for COAD\" paragraph 2", "quote": "The 22 focal adhesion genes were further screened and collinearity was removed to obtain four focal adhesion genes, CAV2, FLT1, THBS3 and VAV3 through the LASSO-Cox algorithm (Figures 3A, B)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36950136", "locator": "sections[19] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A LASSO-Cox-derived four-gene signature (CAV2, FLT1, THBS3 and VAV3) predicted 1-, 2- and 3-year overall survival in the TCGA training cohort with AUCs of 0.661, 0.646 and 0.641, respectively, and showed similar performance in the GSE17538 and GSE39582 validation cohorts.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36950136", "locator": "sections[12] \"3.3 4-Genes signature is a robust prognostic factor for COAD\" paragraph 2", "quote": "The model-predicted AUCs for 1-, 2-, and 3-year OS in the training group were 0.661, 0.646, and 0.641, validating the signature’s predictive performance (Figure 3H), we got similar results in the GSE17538 (Figure 3I), GSE39582 (Figure 3J) test datasets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A LASSO-Cox-derived four-gene signature (CAV2, FLT1, THBS3 and VAV3) predicted 1-, 2- and 3-year overall survival in the TCGA training cohort with AUCs of 0.661, 0.646 and 0.641, respectively, and showed similar performance in the GSE17538 and GSE39582 validation cohorts.", "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:36950136"], "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. 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