Identification of Lactate-Related Gene Signature for Prediction of Progression and Immunotherapeutic Response in Skin Cutaneous Melanoma.

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The potential function of lactate, a main metabolic product in the tumor microenvironment (TME) of SKCM, remains unclear. In this study, we systemically analyzed the predictive value of lactate-related genes (LRGs) for prognosis and response to immune checkpoint inhibitors (ICIs) in SKCM patients included from The Cancer Genome Atlas (TCGA) database. Cluster 3, by consensus clustering for 61 LRGs, manifested a worse clinical outcome, attributed to the overexpression of malignancy marks. In addition, we created a prognostic prediction model for high- and low-risk patients and verified its performance in a validation cohort, GSE65904. Between TME and the risk model, we found a negative relation of the immunocyte infiltration levels with patients' risk scores. The low-risk cases had higher ICI expression and could benefit better from ICIs relative to the high-risk cases. Thus, the lactate-related prognosis risk signature may comprehensively provide a basis for future investigations on immunotherapeutic treatment for SKCM.", "claims": [{"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: https://portal.gdc.cancer.gov/, https://gtexportal.org/home/, and https://www.ncbi.nlm.nih.gov/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35265521", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: https://portal.gdc.cancer.gov/, https://gtexportal.org/home/, and https://www.ncbi.nlm.nih.gov/."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The signature-based risk score was found to be significantly related to OS in univariate Cox analysis (HR = 2.017, P < 0.001) ( Figure 6F ).", "kind": "quantitative", "target": {"value": 2.017, "unit": "hazard ratio", "tolerance": null, "source": "The signature-based risk score was found to be significantly related to OS in univariate Cox analysis (HR = 2.017, P < 0.001) ( Figure 6F )."}, "evidence": [{"asset": "source:pmid:35265521", "locator": "sections[18] \"Relationship Between the Risk Score and Clinical Features\" paragraph 4", "quote": "The signature-based risk score was found to be significantly related to OS in univariate Cox analysis (HR = 2.017, P < 0.001) ( Figure 6F )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The signature-based risk score was found to be significantly related to OS in univariate Cox analysis (HR = 2.017, P < 0.001) ( Figure 6F ).", "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:35265521"], "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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