Identification and validation of a signature involving voltage-gated chloride ion channel genes for prediction of prostate cancer recurrence.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36246902", "kind": "science-record", "revision": 4, "content_hash": "sha256:1d9cd9794ec0d1edbc6cf23bcd8c304bc995470917f07e39a76ebd15140cd1e8", "created_at": "2026-11-01T18:15:37Z", "updated_at": "2026-11-01T22:07:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of a signature involving voltage-gated chloride ion channel genes for prediction of prostate cancer recurrence.", "doi": "10.3389/fendo.2022.1001634", "pmid": "36246902", "authors": ["Yong Luo", "Xiaopeng Liu", "Xiaoxiao Li", "Weide Zhong", "Jingbo Lin", "Qingbiao Chen"], "journal": "Frontiers in endocrinology", "year": 2022, "abstract": "Voltage-gated chloride ion channels (CLCs) are transmembrane proteins that maintain chloride ion homeostasis in various cells. Accumulating studies indicated CLCs were related to cell growth, proliferation, and cell cycle. Nevertheless, the role of CLCs in prostate cancer (PCa) has not been systematically profiled. The purpose of this study was to investigate the expression profiles and biofunctions of CLCs genes, and construct a novel risk signature to predict biochemical recurrence (BCR) of PCa patients. We identified five differentially expressed CLCs genes in our cohort and then constructed a signature composed of CLCN2 and CLCN6 through Lasso-Cox regression analysis in the training cohort from the Cancer Genome Atlas (TCGA). The testing and entire cohorts from TCGA and the GSE21034 from the Gene Expression Omnibus (GEO) were used as internal and independent external validation datasets. This signature could divide PCa patients into the high and low risk groups with different prognoses, was apparently correlated with clinical features, and was an independent excellent prognostic indicator. Enrichment analysis indicated our signature was primarily concentrated in cellular process and metabolic process. The expression patterns of CLCN2 and CLCN6 were detected in our own cohort based immunohistochemistry staining, and we found CLCN2 and CLCN6 were highly expressed in PCa tissues compared with benign tissues and positively associated with higher Gleason score and shorter BCR-free time. Functional experiments revealed that CLCN2 and CLCN6 downregulation inhibited cell proliferation, colony formation, invasion, and migration, but prolonged cell cycle and promoted apoptosis. Furthermore, Seahorse assay showed that silencing CLCN2 or CLCN6 exerted potential inhibitory effects on energy metabolism in PCa. Collectively, our signature could provide a novel and robust strategy for the prognostic evaluation and improve treatment decision making for PCa patients.", "claims": [{"id": "claim-method", "statement": "We performed Lasso regression analysis in the training cohort and two CLCs (CLCN2 and CLCN6) were used to construct the signature in PCa.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36246902", "locator": "sections[13] \"Development and evaluation of a CLCs signature\" paragraph 2", "quote": "We performed Lasso regression analysis in the training cohort and two CLCs (CLCN2 and CLCN6) were used to construct the signature in PCa."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36246902", "locator": "sections[23] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using TCGA-PRAD training, testing, and entire cohorts with GSE21034 as an independent external validation, the CLCN2–CLCN6 signature predicted biochemical recurrence with AUCs of 0.749, 0.674, and 0.754 at 1, 2, and 3 years in the training cohort.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36246902", "locator": "sections[13] \"Development and evaluation of a CLCs signature\" paragraph 2", "quote": "We split PCa patients into the high-risk and low-risk groups with the median risk score as the threshold. Survival analysis indicated that the BCR-free time of the high risk PCa patients was markedly shorter than that of its counterpart ( Figure 3A ), which was validated in internal and external cohorts, namely the testing TCGA-PRAD cohort, the entire TCGA-PRAD cohort, and GSE21034 cohort ( Figures 3B-D )."}, {"asset": "source:pmid:36246902", "locator": "sections[13] \"Development and evaluation of a CLCs signature\" paragraph 2", "quote": "The AUC value was 0.749, 0.674, and 0.754 at 1-, 2-, and 3- years in the training cohort, respectively ( Figure 3A )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using TCGA-PRAD training, testing, and entire cohorts with GSE21034 as an independent external validation, the CLCN2–CLCN6 signature predicted biochemical recurrence with AUCs of 0.749, 0.674, and 0.754 at 1, 2, and 3 years in the training cohort.", "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:36246902"], "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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