Zhu Yajing, Zhang Pan
Department of Infectious Diseases, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Sci Rep. 2025 Apr 13;15(1):12740. doi: 10.1038/s41598-025-96488-4.
Hepatocellular carcinoma and cholangiocarcinoma, the two predominant histological subtypes of primary liver cancer, are characterized by a high global incidence and poor prognosis. Moreover, the therapeutic options are still limited, with surgical intervention being the predominant approach. Anchorage-Dependent Cell Death (Anoikis) is a form of regulated cell death triggered by the detachment of cells from their extracellular matrix, is crucial for maintaining tissue homeostasis. However, tumor cells often evade anoikis, a capability that is essential for their survival in the bloodstream and subsequent metastasis. Our study classified liver cancer into two distinct subtypes, C1 and C2, based on the differential expression of anoikis-related genes. Subtype C1 patients exhibited elevated expression of BRMS1, PTK2, and CASP8, which could serve as potential therapeutic targets for anoikis-based treatments. Conversely, subtype C2 patients showed higher expression of NTRK2, STAT3, SIK1, AKT1, and EGFR, suggesting these genes as promising therapeutic targets for C2 subtype liver cancer. Furthermore, employing Weighted Correlation Network analysis, machine learning models, and experimental validation, we identified NPY1R and HGF as potential biomarkers for the diagnosis and treatment of liver cancer.
肝细胞癌和胆管癌是原发性肝癌的两种主要组织学亚型，其特点是全球发病率高且预后差。此外，治疗选择仍然有限，手术干预是主要方法。锚定依赖性细胞死亡（失巢凋亡）是一种由细胞与其细胞外基质脱离引发的程序性细胞死亡形式，对维持组织稳态至关重要。然而，肿瘤细胞常常逃避失巢凋亡，这种能力对其在血流中的存活及随后的转移至关重要。我们的研究基于失巢凋亡相关基因的差异表达将肝癌分为两种不同的亚型，C1和C2。C1亚型患者表现出BRMS1、PTK2和CASP8的表达升高，这些基因可作为基于失巢凋亡治疗的潜在靶点。相反，C2亚型患者显示出NTRK2、STAT3、SIK1、AKT1和EGFR的更高表达，表明这些基因是C2亚型肝癌有前景的治疗靶点。此外，通过加权相关网络分析、机器学习模型和实验验证，我们确定NPY1R和HGF是肝癌诊断和治疗的潜在生物标志物。
