Background & Aims: Intrahepatic cholangiocarcinoma (ICC) remains a rare malignancy, ranking the leading lethal primary liver cancer worldwide. However, biological functions of integrator complex subunit 8 (INTS8) remain unknown in ICC. Thus, this research aimed to explore the potential role of INTS8, as well as develop a novel diagnosed or therapeutic target in ICC.
Methods: Differently expressed genes in two GEO datasets were obtained by RRA package in R software. The “maftools” package was implemented to visualize the cholangiocarcinoma (CHOL) mutation data in TCGA database. The expression of INTS8 was detected by preforming quantitative reverse transcription-PCR (qRT-PCR) and immunohistochemistry in cell lines and human samples, respectively. The association between subtypes of tumor-infiltrating immune cells (TICs) and INTS8 expression in CHOL was performed by using CIBERSORT tools. We evaluated a correlation between INTS8 expression and mismatch repair genes (MMRs) and DNA methyltransferases in pan-cancer analyses. Finally, the pan-cancer prognostic signatures of INTS8 were identified by univariate analyses.
Results: We obtained the mutation landscape of a RRA gene set in CHOL. The expression of INTS8 was actually upregulated in ICC cell lines and human ICC samples. Furthermore, INTS8 expression is tightly associated with distinct landscape of TICs, the MMRs, and DNA methyltransferases in CHOL. In addition, the high INTS8 expression group presented a significantly poor outcomes, including overall survival (OS), disease-specific survival (DSS) and disease-free interval (DFI) (P < 0.05) in multi-cancers.
Conclusions: INTS8 contributes to the tumorigenesis and progression of ICC. Our study highlights the significant roles of INTS8 in ICC and pan-cancers, providing a valuable molecular target for cancer research.