Background: Nonalcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) is becoming a major health-related problem. The exploration of NASH-related prognostic biomarkers and therapeutic targets is necessary. Methods: Data were downloaded from the GEO database. The "glmnet" package was used to identify differentially expressed genes (DEGs). The prognostic model was constructed by the univariate Cox and LASSO regression analyses. Validation of the expression and prognosis by immunohistochemistry (IHC) in vitro. Drug sensitivity and immune cell infiltration were analyzed by CTR-DB and ImmuCellAI. Results: We constructed a prognostic model that identified the NASH-related gene set (DLAT, IDH3B, and MAP3K4), which was validated in a real-world cohort. Next, seven prognostic transcription factors (TFs) were identified. The prognostic ceRNA network included three mRNAs, four miRNAs, and seven lncRNAs. Finally, we found that the gene set was associated with drug response which was validated in six clinical trial cohorts. Moreover, the expression level of the gene set was inversely correlated with CD8 T cell infiltration in HCC. Conclusions: We established a NASH-related prognostic model. Upstream transcriptome analysis and the ceRNA network provided clues for mechanism exploration. The mutant profile, drug sensitivity, and immune infiltration analysis further guided precise diagnosis and treatment strategies.

中文翻译：

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与肝细胞癌中药物敏感性和免疫浸润相关的 NASH 相关预后生物标志物的多组学分析。

背景：非酒精性脂肪性肝炎 (NASH) 驱动的肝细胞癌 (HCC) 正在成为与健康相关的主要问题。探索与 NASH 相关的预后生物标志物和治疗靶点是必要的。方法：数据从 GEO 数据库下载。“glmnet”包用于识别差异表达基因 (DEG)。预后模型由单变量 Cox 和 LASSO 回归分析构建。通过体外免疫组织化学 (IHC) 验证表达和预后。通过 CTR-DB 和 ImmuCellAI 分析药物敏感性和免疫细胞浸润。结果：我们构建了一个预后模型，该模型识别了 NASH 相关基因组（DLAT、IDH3B 和 MAP3K4），该模型在真实世界队列中得到验证。接下来，确定了七个预后转录因子 (TF)。预后 ceRNA 网络包括三个 mRNA、四个 miRNA 和七个 lncRNA。最后，我们发现基因集与药物反应相关，这在六个临床试验队列中得到了验证。此外，该基因组的表达水平与 HCC 中的 CD8 T 细胞浸润呈负相关。结论：我们建立了 NASH 相关的预后模型。上游转录组分析和 ceRNA 网络为机制探索提供了线索。突变谱、药物敏感性和免疫浸润分析进一步指导了精确的诊断和治疗策略。该基因组的表达水平与HCC中的CD8 T细胞浸润呈负相关。结论：我们建立了 NASH 相关的预后模型。上游转录组分析和 ceRNA 网络为机制探索提供了线索。突变谱、药物敏感性和免疫浸润分析进一步指导了精确的诊断和治疗策略。该基因组的表达水平与HCC中的CD8 T细胞浸润呈负相关。结论：我们建立了 NASH 相关的预后模型。上游转录组分析和 ceRNA 网络为机制探索提供了线索。突变谱、药物敏感性和免疫浸润分析进一步指导了精确的诊断和治疗策略。