Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi'an 710032, China.
Department of General Surgery, Air Force Hospital of Western Theater Command, Chengdu 610021, China.
Dis Markers. 2022 Sep 5;2022:3594901. doi: 10.1155/2022/3594901. eCollection 2022.
Hepatocellular carcinoma (HCC) is a common type of malignant tumor with high morbidity and mortality. The oxidative phosphorylation (OXPHOS) metabolic pathway produces adenosine triphosphate (ATP) by delivering electrons to transmembrane protein complexes in the mitochondria. This research was dedicated to identifying an OXPHOS-associated signature for the assessment of prognosis of HCC patients. A total of 371 HCC patients from the Cancer Genome Atlas (TCGA) and 231 HCC patients from the International Cancer Genome Consortium (ICGC) with RNA expression data and clinical data were employed as construction and validation cohorts, respectively. The least absolute shrinkage and selection operator (LASSO) Cox regression was applied to establish a multigene signature in the TCGA cohort, and the ICGC cohort was used for validation. The prognostic value of the risk signature was evaluated using univariate and multivariate Cox regression, Kaplan-Meier curves, and receiver operating characteristic (ROC) curves. The potential enrichment of biological functions was investigated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Meanwhile, we analyzed the correlation between the risk score and the tumor microenvironment (TME). A five-gene signature including ATP6V0B, ATP6V1C1, ATP6V1E1, TIMM9, and UQCRH was identified by LASSO Cox regression to classify patients into low- and high-risk groups. ROC curve analysis indicated that the five-gene signature is a prospective prognostic factor in HCC patients. Univariate and multivariate Cox regression analyses demonstrated that the risk score was an independent prognostic factor for overall survival (OS). Functional analysis showed that differentially expressed genes (DEGs) between the low- and high-risk groups were enriched in mitosis and the cell cycle pathway. In addition, the five-gene signature was associated with innate immune cell infiltration, immune subtypes, and tumor stemness. A novel OXPHOS-associated gene signature can be used for prognostic prediction for patients with HCC.
肝细胞癌（HCC）是一种常见的恶性肿瘤，发病率和死亡率都很高。氧化磷酸化（OXPHOS）代谢途径通过将电子递送到线粒体跨膜蛋白复合物来产生三磷酸腺苷（ATP）。本研究旨在确定与 OXPHOS 相关的特征，以评估 HCC 患者的预后。共纳入来自癌症基因组图谱（TCGA）的 371 名 HCC 患者和来自国际癌症基因组联盟（ICGC）的 231 名 HCC 患者，分别作为构建和验证队列，这些患者均具有 RNA 表达数据和临床数据。采用最小绝对收缩和选择算子（LASSO）Cox 回归在 TCGA 队列中建立多基因特征，并在 ICGC 队列中进行验证。采用单因素和多因素 Cox 回归、Kaplan-Meier 曲线和受试者工作特征（ROC）曲线评估风险特征的预后价值。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析探讨潜在的生物学功能富集情况。同时，我们分析了风险评分与肿瘤微环境（TME）的相关性。通过 LASSO Cox 回归，鉴定出包括 ATP6V0B、ATP6V1C1、ATP6V1E1、TIMM9 和 UQCRH 在内的 5 个基因特征，可将患者分为低风险和高风险组。ROC 曲线分析表明，该 5 个基因特征是 HCC 患者的潜在预后因素。单因素和多因素 Cox 回归分析表明，风险评分是总生存期（OS）的独立预后因素。功能分析表明，低风险和高风险组之间的差异表达基因（DEGs）富集在有丝分裂和细胞周期途径中。此外，该 5 个基因特征与固有免疫细胞浸润、免疫亚型和肿瘤干性有关。一个新的与 OXPHOS 相关的基因特征可用于预测 HCC 患者的预后。
