Due to falling prevalence of viral hepatitis (VH), obesity, alcoholism and related liver diseases have become increasingly frequent and important as causes of hepatocellular carcinoma (HCC). However, mechanisms underlying hepatocarcinogenesis and tumor progression in VH-negative HCC remain poorly understood. Long non-coding RNAs (lncRNAs) have been implicated in pathogenesis of human diseases, including HCC. Here, by analyzing 20 clinical samples’ RNA-sequencing data generated from 8 VH-negative and 2 VH-positive HCC patients, we have identified and characterized 1,514 candidate lncRNAs. For differentially expressed genes (DEGs) between tumor tissues and adjacent non-tumor tissues (P < 0.05, |FC| > 2), the upregulated genes were mainly involved in the cell proliferation, and the downregulated genes mediated the metabolic processes and responses to oxidative stress, inflammation and toxic substances. Furthermore, the lncRNA-mRNA co-expression network was constructed, by which two genetic aberrations with high frequency in HCC, SPATA46 and TMEM78, were identified. In addition, we identified 16 DEGs between tumor issues from VH-negative and VH-positive HCC patients with aim to explore gene expression differences that could be involved in the pathogenesis of HCC with varying etiology. In conclusion, we performed the comprehensive analysis of lncRNA and mRNA expression profiles, which could provide valuable insights into the underlying genetic alteration in non-virus associated HCC.

由于病毒性肝炎（VH）患病率下降，肥胖、酗酒和相关肝脏疾病作为肝细胞癌（HCC）的原因变得越来越常见和重要。然而，VH 阴性 HCC 的肝癌发生和肿瘤进展的机制仍知之甚少。长链非编码 RNA (lncRNA) 与包括 HCC 在内的人类疾病的发病机制有关。在这里，通过分析 8 名 VH 阴性和 2 名 VH 阳性 HCC 患者生成的 20 个临床样本的 RNA 测序数据，我们鉴定并表征了 1,514 个候选 lncRNA。对于肿瘤组织和邻近非肿瘤组织之间的差异表达基因（DEG）（ P < 0.05，|FC| > 2），上调基因主要参与细胞增殖，下调基因介导代谢过程和反应。氧化应激、炎症和有毒物质。此外，构建了lncRNA-mRNA共表达网络，通过该网络鉴定了HCC中出现频率较高的两个遗传畸变：SPATA46和TMEM78。此外，我们还确定了 VH 阴性和 VH 阳性 HCC 患者肿瘤问题之间的 16 个 DEG，旨在探索可能参与不同病因 HCC 发病机制的基因表达差异。总之，我们对 lncRNA 和 mRNA 表达谱进行了全面分析，这可以为非病毒相关 HCC 的潜在遗传改变提供有价值的见解。