Central Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.
Department of Clinical Nutrition, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.
Oxid Med Cell Longev. 2022 Sep 19;2022:6595989. doi: 10.1155/2022/6595989. eCollection 2022.
To offer new prognostic evaluations by exploring potentially distinctive genetic features of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).
There were 12 samples for gene expression profiling processes in this study. These included three HCC lesion samples and their matched adjacent nontumor liver tissues obtained from patients with HCC, as well as three ICC samples and their controls collected similarly. In addition to the expression matrix generated on our own, profiles of other cohorts from The Cancer Genome Atlas (TCGA) program and the Gene Expression Omnibus (GEO) were also employed in later bioinformatical analyses. Differential analyses, functional analyses, protein interaction network analyses, and gene set variation analyses were used to identify key genes. To establish the prognostic models, univariate/multivariate Cox analyses and subsequent stepwise regression were applied, with the Akaike information criterion evaluating the goodness of fitness.
The top three pathways enriched in HCC were all metabolism-related; they were fatty acid degradation, retinol metabolism, and arachidonic acid metabolism. In ICC, on the other hand, additional pathways related to fat digestion and absorption and cholesterol metabolism were identified. Consistent characteristics of such a metabolic landscape were observed across different cohorts. A prognostic risk score model for calculating HCC risk was constructed, consisting of , , , , and . This signature predicts the 3-year survival with an AUC area of 0.708 (95%CI = 0.644 to 0.772). For calculating the risk of ICC, a prognostic risk score model was built upon the expression levels of , , and . This signature predicts the 3-year survival with an AUC area of 0.806 (95% CI = 0.664 to 0.947).
HCC and ICC share commonly abrupted pathways associated with the metabolism of fatty acids, retinol, arachidonic acids, and drugs, indicating similarities in their pathogenesis as primary liver cancers. On the flip side, these two types of cancer possess distinctive promising biomarkers for predicting overall survival or potential targeted therapies.
通过探索肝细胞癌（HCC）和肝内胆管癌（ICC）潜在的独特基因特征，提供新的预后评估。
本研究共进行了 12 例样本的基因表达谱分析。其中包括 3 例 HCC 病变样本及其从 HCC 患者中获得的配对相邻非肿瘤肝组织，以及 3 例 ICC 样本及其类似收集的对照。除了我们自己生成的表达矩阵外，还使用了来自癌症基因组图谱（TCGA）计划和基因表达综合数据库（GEO）的其他队列的图谱进行后续的生物信息学分析。采用差异分析、功能分析、蛋白质相互作用网络分析和基因集变异分析来识别关键基因。为了建立预后模型，应用单变量/多变量 Cox 分析和随后的逐步回归，使用 Akaike 信息准则评估拟合优度。
在 HCC 中，富集的前三个通路均与代谢有关，分别为脂肪酸降解、视黄醇代谢和花生四烯酸代谢。而在 ICC 中，还确定了与脂肪消化和吸收以及胆固醇代谢有关的其他通路。在不同的队列中观察到这种代谢特征的一致特征。构建了用于计算 HCC 风险的预后风险评分模型，该模型由、、、和组成。该标志物预测 3 年生存率的 AUC 面积为 0.708（95%CI=0.644 至 0.772）。为了计算 ICC 的风险，构建了一个基于、和表达水平的预后风险评分模型。该标志物预测 3 年生存率的 AUC 面积为 0.806（95%CI=0.664 至 0.947）。
HCC 和 ICC 共享与脂肪酸、视黄醇、花生四烯酸和药物代谢相关的共同中断途径，表明作为原发性肝癌，它们在发病机制上存在相似性。另一方面，这两种类型的癌症具有独特的有前途的生物标志物，可用于预测总生存率或潜在的靶向治疗。
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