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

<h4>Background</h4>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 (<i>ESCO2</i>) as a core candidate, and validate its role experimentally.<h4>Methods</h4>The CCA data were downloaded using the Gene Expression Comprehensive Database and the Cancer Genome Atlas, the core gene <i>ESCO2</i> 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 <i>ESCO2</i> on CCA cells and its oncogenic effects were investigated by cell and animal experiments.<h4>Results</h4>A total of 1,372 differential genes were screened in this study, with 742 up-regulated genes including <i>ESCO2</i> and 630 down-regulated genes. Patients with high <i>ESCO2</i> expression had a poorer prognosis and were significantly associated with N stage. Immune infiltration analysis revealed that <i>ESCO2</i> expression was negatively correlated with <i>CD8A</i> and <i>FGFBP2</i>. Cellular experiments showed that <i>ESCO2</i> was significantly up-regulated in CCA cells. <i>ESCO2</i> overexpression promotes CCA cell proliferation and inhibits apoptosis. <i>In vivo</i> experiments confirmed that <i>ESCO2</i> promotes tumor growth and shortens survival in mice.<h4>Conclusions</h4><i>ESCO2</i> 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.