Gene expression profile of anoikis reveals new subtypes of liver cancer and discovery of therapeutic targets and biomarkers

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.