Comprehensive Molecular Analyses of a Six-Gene Signature for Predicting Late Recurrence of Hepatocellular Carcinoma.

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We sought to develop a novel tool to stratify patients with different LR risk for tailoring decision-making for postoperative recurrence surveillance and therapy modalities. We retrospectively enrolled two independent public cohorts and 103 HCC tissues. Using LASSO logical analysis, a six-gene model was developed in the The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA-LIHC) and independently validated in GSE76427. Further experimental validation using qRT-PCR assays was performed to ensure the robustness and clinical feasible of this signature. We developed a novel LR-related signature consisting of six genes. This signature was validated to be significantly associated with dismal recurrence-free survival in three cohorts TCGA-LIHC, GSE76427, and qPCR assays [HR: 2.007 (1.200-3.357), p = 0.008; HR: 2.171 (1.068, 4.412), p-value = 0.032; HR: 3.383 (2.100, 5.450), p-value <0.001]. More importantly, this signature displayed robust discrimination in predicting the LR risk, with AUCs being 0.73 (TCGA-LIHC), 0.93 (GSE76427), and 0.85 (in-house cohort). Furthermore, we deciphered the specific landscape of molecular alterations among patients in nonrecurrence (NR) and LR group to analyze the mechanism contributing to LR. For high-risk group, we also identified several potential drugs with specific sensitivity to high- and low-risk groups, which is vital to improve prognosis of LR-HCC after surgery. We discovered and experimentally validated a novel gene signature with powerful performance for identifying patients at high LR risk in stages I-III HCC.", "claims": [{"id": "claim-method", "statement": "To search the genes significantly related to LR in HCC, we initially filtered LR-related genes in TCGA-LIHC and GSE76427 using DEseq2 and limma R packages, separately, and the adjusted p-value <0.05 was adopted for further analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34568069", "locator": "sections[4] \"Identification of Significantly LR-Related Genes in HCC\" paragraph 2", "quote": "To search the genes significantly related to LR in HCC, we initially filtered LR-related genes in TCGA-LIHC and GSE76427 using DEseq2 and limma R packages, separately, and the adjusted p-value <0.05 was adopted for further analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The liver hepatocellular carcinoma (LIHC) transcriptome profiles with clinical data were obtained from The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/) and the chip-array profiles with clinical data were downloaded from Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34568069", "locator": "sections[3] \"Data Acquisition and Arrangement\" paragraph 2", "quote": "The liver hepatocellular carcinoma (LIHC) transcriptome profiles with clinical data were obtained from The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/) and the chip-array profiles with clinical data were downloaded from Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:34568069"], "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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