Carcinogenic role of ESCO2 in cholangiocarcinoma: integration of bioinformatics analysis and experimental validation

Cholangiocarcinoma (CCA) is a highly heterogeneous biliary malignancy with a poor prognosis. Finding early diagnosis and therapeutic targets for CCA is of great importance. The aim of this study was to screen for key genes involved in CCA using bioinformatics analysis, identify establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) as a core candidate, and validate its role experimentally.

The CCA data were downloaded using the Gene Expression Comprehensive Database and the Cancer Genome Atlas, the core gene ESCO2 with strong correlation with CCA was screened by raw letter analysis, and the prognostic value of key CCA genes was analyzed by Kaplan-Meier. The effects of ESCO2 on CCA cells and its oncogenic effects were investigated by cell and animal experiments.

A total of 1,372 differential genes were screened in this study, with 742 up-regulated genes including ESCO2 and 630 down-regulated genes. Patients with high ESCO2 expression had a poorer prognosis and were significantly associated with N stage. Immune infiltration analysis revealed that ESCO2 expression was negatively correlated with CD8A and FGFBP2. Cellular experiments showed that ESCO2 was significantly up-regulated in CCA cells. ESCO2 overexpression promotes CCA cell proliferation and inhibits apoptosis. In vivo experiments confirmed that ESCO2 promotes tumor growth and shortens survival in mice.

ESCO2 is a key regulatory gene affecting the development of CCA and plays an important role in CCA cell proliferation, which could be a new target for CCA diagnosis and treatment.