Huang Fei, Yaermaimaiti Dilinaer, Ding Guanxin, Zhao Lijun, Zhou Jing, Wu Shunhua
Department of Occupational and Environmental Health, School of Public Health, Xinjiang Medical University, Urumqi 830011, China.
Department of Pathology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830011, China.
J Oncol. 2023 Feb 20;2023:2973480. doi: 10.1155/2023/2973480. eCollection 2023.
The clinical behavior and molecular mechanisms of hepatocellular carcinoma (HCC) are complex and highly variable, limiting the discovery of new targets and therapies in clinical research. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is one of the tumor suppressor genes. It is of great interest to discover the role of unexplored correlation among PTEN, the tumor immune microenvironment, and autophagy-related signaling pathways and to construct a reliable risk model for prognosis during HCC progression.
We first performed differential expression analysis on the HCC samples. By using Cox regression and LASSO analysis, we determined the DEGs contributing to the survival benefit. In addition, the gene set enrichment analysis (GSEA) was performed to identify potential molecular signaling pathways regulated by the PTEN gene signature, autophagy, and autophagy-related pathways. ESTIMATE was also employed for evaluating the composition of immune cell populations.
We found a significant correlation between PTEN expression and the tumor immune microenvironment. The low-PTEN expression group had higher immune infiltration and lower expression of immune checkpoints. In addition, PTEN expression was found to be positively correlated with autophagy-related pathways. Then, differentially expressed genes between tumor and tumor-adjacent samples were screened, and 2895 genes were significantly associated with both PTEN and autophagy. Based on PTEN-related genes, we identified 5 key prognostic genes, including BFSP1, PPAT, EIF5B, ASF1A, and GNA14. The 5-gene PTEN-autophagy risk score (RS) model was demonstrated to have favorable performance in the prediction of prognosis.
In summary, our study showed the importance of the PTEN gene and its correlation with immunity and autophagy in HCC. The PTEN-autophagy.RS model we established could be used to predict the prognosis of HCC patients and showed significantly higher prognostic accuracy than the TIDE score in response to immunotherapy.
肝细胞癌（HCC）的临床行为和分子机制复杂且高度可变，限制了临床研究中新靶点和新疗法的发现。10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）是肿瘤抑制基因之一。探索PTEN、肿瘤免疫微环境和自噬相关信号通路之间未被发现的相关性作用，并构建一个可靠的肝癌进展预后风险模型具有重要意义。
我们首先对肝癌样本进行差异表达分析。通过Cox回归和LASSO分析，确定对生存有益的差异表达基因（DEGs）。此外，进行基因集富集分析（GSEA）以识别由PTEN基因特征、自噬和自噬相关通路调控的潜在分子信号通路。还采用ESTIMATE评估免疫细胞群体的组成。
我们发现PTEN表达与肿瘤免疫微环境之间存在显著相关性。PTEN低表达组具有更高的免疫浸润和更低的免疫检查点表达。此外，发现PTEN表达与自噬相关通路呈正相关。然后，筛选肿瘤与癌旁样本之间的差异表达基因，发现2895个基因与PTEN和自噬均显著相关。基于PTEN相关基因，我们鉴定出5个关键预后基因，包括BFSP1、PPAT、EIF5B、ASF1A和GNA14。5基因PTEN-自噬风险评分（RS）模型在预后预测中表现良好。
总之，我们的研究表明PTEN基因及其与肝癌免疫和自噬的相关性的重要性。我们建立的PTEN-自噬.RS模型可用于预测肝癌患者的预后，并且在预测免疫治疗反应方面显示出比TIDE评分显著更高的预后准确性。
