Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang Province, China.
World J Gastroenterol. 2020 Feb 28;26(8):789-803. doi: 10.3748/wjg.v26.i8.789.
Despite significant advances in multimodality treatments, hepatocellular carcinoma (HCC) remains one of the most common malignant tumors. Identification of novel prognostic biomarkers and molecular targets is urgently needed.
To identify potential key genes associated with tumor microenvironments and the prognosis of HCC.
The infiltration levels of immune cells and stromal cells were calculated and quantified based on the ESTIMATE algorithm. Differentially expressed genes (DEGs) between high and low groups according to immune or stromal scores were screened using the gene expression profile of HCC patients in The Cancer Genome Atlas and were further linked to the prognosis of HCC. These genes were validated in four independent HCC cohorts. Survival-related key genes were identified by a LASSO Cox regression model.
HCC patients with a high immune/stromal score had better survival benefits than patients with a low score. A total of 899 DEGs were identified and found to be involved in immune responses and extracellular matrices, 147 of which were associated with overall survival. Subsequently, 52 of 147 survival-related DEGs were validated in additional cohorts. Finally, ten key genes (, , , and ) were selected and used to construct a prognostic gene signature, which presented a good performance in predicting overall survival.
This study extracted a list of genes associated with tumor microenvironments and the prognosis of HCC, thereby providing several valuable directions for the prognostic prediction and molecular targeted therapy of HCC in the future.
尽管多模态治疗取得了重大进展，但肝细胞癌（HCC）仍然是最常见的恶性肿瘤之一。迫切需要确定新的预后生物标志物和分子靶标。
鉴定与肿瘤微环境和 HCC 预后相关的潜在关键基因。
根据 ESTIMATE 算法计算并量化免疫细胞和基质细胞的浸润水平。使用 TCGA 中 HCC 患者的基因表达谱筛选根据免疫或基质评分的高、低组之间的差异表达基因（DEGs），并进一步与 HCC 的预后相关联。在四个独立的 HCC 队列中验证这些基因。通过 LASSO Cox 回归模型确定与生存相关的关键基因。
免疫/基质评分高的 HCC 患者的生存获益优于评分低的患者。共鉴定出 899 个 DEGs，这些基因与免疫反应和细胞外基质有关，其中 147 个与总生存期相关。随后，在其他队列中验证了这 147 个与生存相关的 DEGs 中的 52 个。最后，选择了 10 个关键基因（,,, 和 ）构建预后基因特征，该特征在预测总生存期方面表现良好。
本研究提取了一组与 HCC 肿瘤微环境和预后相关的基因，为 HCC 的预后预测和分子靶向治疗提供了有价值的方向。
