Zhou Xuan, Wei Bai, Wang Yan, Liu Mingjie, Guo Xiangru, Duan Yuting
Department of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Yanhu Avenue, Wuchang, Wuhan, 430077, Hubei, People's Republic of China.
Discov Oncol. 2025 Jun 10;16(1):1051. doi: 10.1007/s12672-025-02840-5.
Intrahepatic cholangiocarcinoma is a malignant tumor of hepatobiliary epithelial cells. In recent years, its incidence has gradually increased. It has a very high fatality rate and low survival rate, and the existing predictive factors for intrahepatic cholangiocarcinoma are unclear. The role of anoikis, a form of programmed cell death, in intrahepatic cholangiocarcinoma is not fully understood. This study focuses on identifying and analyzing anoikis-related differentially expressed genes in intrahepatic cholangiocarcinoma, aiming to enhance our understanding of potential treatment strategies and prognosis of intrahepatic cholangiocarcinoma.
In our study, we employed a clustering algorithm to classify samples from The Cancer Genome Atlas (TCGA) based on differentially expressed overlapping anoikis-related genes. Subsequently, we utilized Weighted Gene Co-expression Network Analysis (WGCNA) to identify highly correlated genes and constructed a prognostic risk model based on univariate Cox proportional hazard regression. We validated the model's reliability using external datasets from the International Cancer Genome Consortium (ICGC) and the Gene Expression Omnibus (GEO). Finally, we used the CIBERSORT algorithm to investigate the correlation between risk scores and immune infiltration.
The results showed that the TCGA cohort could be divided into 2 subgroups, among which subgroup B had a lower survival probability. We identified three prognostic genes (EGF, BNIP3, TDGF1) associated with anorexia. The prognostic risk model effectively predicted overall survival and was validated in ICGC and GEO data sets. Furthermore, there were significant correlations between infiltrating immune cells and prognostic genes and risk scores.
We identified subgroups and prognostic genes associated with ICCA dysregulation, which are important for understanding the treatment and prognosis of ICCA.
肝内胆管癌是一种肝胆上皮细胞恶性肿瘤。近年来，其发病率逐渐上升。它具有很高的死亡率和低生存率，且目前肝内胆管癌的预测因素尚不清楚。失巢凋亡作为一种程序性细胞死亡形式，在肝内胆管癌中的作用尚未完全明确。本研究聚焦于识别和分析肝内胆管癌中与失巢凋亡相关的差异表达基因，旨在加深我们对肝内胆管癌潜在治疗策略和预后的理解。
在我们的研究中，我们采用聚类算法根据差异表达的重叠失巢凋亡相关基因对来自癌症基因组图谱（TCGA）的样本进行分类。随后，我们利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比例风险回归构建了一个预后风险模型。我们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）的外部数据集验证了该模型的可靠性。最后，我们使用CIBERSORT算法研究风险评分与免疫浸润之间的相关性。
结果显示，TCGA队列可分为2个亚组，其中B亚组的生存概率较低。我们鉴定出三个与失巢凋亡相关的预后基因（表皮生长因子、BNIP3、畸胎瘤衍生生长因子1）。该预后风险模型有效地预测了总生存期，并在ICGC和GEO数据集中得到验证。此外，浸润性免疫细胞与预后基因和风险评分之间存在显著相关性。
我们鉴定出了与肝内胆管癌失调相关的亚组和预后基因，这对于理解肝内胆管癌的治疗和预后具有重要意义。
