International Cancer Institute, Peking University Health Science Center, Beijing 100191, China.
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
Int J Mol Sci. 2023 Feb 2;24(3):2862. doi: 10.3390/ijms24032862.
Resistance to anoikis is a key characteristic of many cancer cells, promoting cell survival. However, the mechanism of anoikis in hepatocellular carcinoma (HCC) remains unknown. In this study, we applied differentially expressed overlapping anoikis-related genes to classify The Cancer Genome Atlas (TCGA) samples using an unsupervised cluster algorithm. Then, we employed weighted gene coexpression network analysis (WGCNA) to identify highly correlated genes and constructed a prognostic risk model based on univariate Cox proportional hazards regression. This model was validated using external datasets from the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). Finally, we used a CIBERSORT algorithm to investigate the correlation between risk score and immune infiltration. Our results showed that the TCGA cohorts could be divided into two subgroups, with subgroup A having a lower survival probability. Five genes (, , , and DAP3) were identified as anoikis-related prognostic genes. Moreover, the prognostic risk model effectively predicted overall survival, which was validated using ICGC and GEO datasets. In addition, there was a strong correlation between infiltrating immune cells and prognostic genes and risk score. In conclusion, we identified anoikis-related subgroups and prognostic genes in HCC, which could be significant for understanding the molecular mechanisms and treatment of HCC.
抗失巢凋亡是许多癌细胞的一个关键特征，促进细胞存活。然而，肝细胞癌（HCC）中失巢凋亡的机制尚不清楚。在这项研究中，我们应用差异表达的重叠失巢凋亡相关基因，使用无监督聚类算法对癌症基因组图谱（TCGA）样本进行分类。然后，我们采用加权基因共表达网络分析（WGCNA）来识别高度相关的基因，并基于单变量 Cox 比例风险回归构建预后风险模型。该模型使用来自国际癌症基因组联盟（ICGC）和基因表达综合数据库（GEO）的外部数据集进行验证。最后，我们使用 CIBERSORT 算法来研究风险评分与免疫浸润之间的相关性。我们的研究结果表明，TCGA 队列可以分为两个亚组，亚组 A 的生存概率较低。鉴定出 5 个与失巢凋亡相关的预后基因（、、、和 DAP3）。此外，预后风险模型能够有效地预测总生存期，在 ICGC 和 GEO 数据集上得到验证。此外，浸润免疫细胞与预后基因和风险评分之间存在很强的相关性。总之，我们鉴定了 HCC 中的失巢凋亡相关亚群和预后基因，这可能对理解 HCC 的分子机制和治疗具有重要意义。
