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pmid:35966318
Novel hypoxia features with appealing implications in discriminating the prognosis, immune escape and drug responses of 947 hepatocellular carcinoma patients.
Mingyuan Luan · Hongzong Si
Translational cancer research · 2022 doi:10.21037/tcr-22-253
Paper
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Experiment
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Data
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Complete file
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This study aimed to explore and elucidate how hypoxia affect prognosis, immune escape and drug responses in HCC.\nMethods: HCC-specific hypoxia signatures were identified based on the intersect of differentially expressed genes (DEGs) of GSE41666 and GSE15366. The hypoxia score was calculated using the gene set variation analysis (GSVA) function and validated on GSE18494. We collected five cohorts [The Cancer Genome Atlas (TCGA), GSE14520, GSE39791, GSE36376, GSE57957] for further analysis. First, we analyzed the effect of the hypoxia score on prognosis. Next, we systematically analyzed the potential hypoxia-related immune escape mechanisms and the effect of hypoxia upon immunotherapy. Then, we predicted and screened potential sensitive drugs for HCC patients with high hypoxia levels using machine learning and docking.\nResults: We constructed a novel HCC-specific hypoxia score and undertook further analysis in five cohorts (TCGA, GSE14520, GSE39791, GSE36376, GSE57957). We observed that patients with high hypoxia scores exhibited worse overall survival (OS) in TCGA and GSE14520. We also constructed a hypoxia-related nomogram that had good performance in predicting HCC patients' prognosis. Furthermore, patients with lower hypoxia scores had a lower risk of immune escape and thus may benefit from immunotherapy. Finally, we predicted and screened VLX600 as the candidate drug for HCC patients with high hypoxia scores. We further explored and elucidated why VLX600 was more sensitive in HCC patients with high hypoxia than with low hypoxia HCC patients using weighted gene co-expression network analysis (WGCNA).\nConclusions: This study provides further evidence of the link between hypoxia and prognosis and immune escape in HCC patients. Moreover, our research screened VLX600 as a potential drug for HCC patients with high hypoxia levels and elucidated the potential mechanism.", "claims": [{"id": "claim-method", "statement": "For comparisons of two groups, we used wilcoxon rank-sum test. For comparisons of more than two groups, we used Kruskal-Wallis tests. The two-sided Fisher’s exact test was performed for the contingency tables. All statistical P values were two-sided. The survival curves of each data set were generated by Kaplan-Meier analysis, and statistically significant differences were determined through the log-rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35966318", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "For comparisons of two groups, we used wilcoxon rank-sum test. For comparisons of more than two groups, we used Kruskal-Wallis tests. The two-sided Fisher’s exact test was performed for the contingency tables. All statistical P values were two-sided. The survival curves of each data set were generated by Kaplan-Meier analysis, and statistically significant differences were determined through the log-rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "TCGA gene expression data [transcripts per million (TPM) and row counts], copy number data, mutation data, clinical data and sample information of HCC were downloaded from Xena (13).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35966318", "locator": "sections[3] \"HCC data sets downloading and preprocessing\" paragraph 2", "quote": "TCGA gene expression data [transcripts per million (TPM) and row counts], copy number data, mutation data, clinical data and sample information of HCC were downloaded from Xena (13)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study constructed a novel HCC-specific hypoxia score that was associated with prognosis and immune escape and identified VLX600 as a potential drug for HCC patients with high hypoxia levels.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35966318", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We constructed a novel HCC-specific hypoxia score and undertook further analysis in five cohorts (TCGA, GSE14520, GSE39791, GSE36376, GSE57957)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The study constructed a novel HCC-specific hypoxia score that was associated with prognosis and immune escape and identified VLX600 as a potential drug for HCC patients with high hypoxia levels.", "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:35966318"], "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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