CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) responds poorly to standard chemotherapy or targeted therapy; hence, exploration for novel therapeutic targets is urgently needed. CEP192 protein is indispensable for centrosome amplification, which has been extensively characterized in both hematological malignancies and solid tumors. Here, we combined bioinformatics and experimental approaches to assess the potential of CEP192 as a prognostic and therapeutic target in HCC. CEP192 expression increased with tumor stage and was associated with poor clinicopathologic features, frequent recurrence, and higher mortality. Upon single-cell RNA sequencing, CEP192 was found to be involved in the proliferation and self-renewal of hepatic progenitor-like cells. This observation was further evidenced using CEP192 silencing, which prevented tumor cell proliferation and self-renewal by arresting cells in the G0/G1 phase of the cell cycle. Notably, CEP192 was highly correlated with multiple tumor-associated cytokine ligand–receptor axes, including IL11–IL11RA, IL6–IL6R, and IL13–IL13RA1, which could promote interactions between hepatic progenitor-like cells, PLVAP+ endothelial cells, tumor-associated macrophages, and CD4+ T cells. Consequently, CEP192 expression was closely associated with an immunosuppressive tumor microenvironment and low immunophenoscores, making it a potential predictor of response to immune checkpoint inhibitors. Taken together, our results unravel a novel onco-immunological role of CEP192 in establishing the immunosuppressive tumor microenvironment and provide a novel biomarker, as well as a potential target for therapeutic intervention of HCC.

Centrosomes and associated proteins in pathogenesis and treatment of breast cancer

“…However, little is known about its tumor-promoting properties in breast cancer. A study by Liu et al did identify CEP192 as a novel prognostic marker in hepatocellular carcinoma based on increased expression with tumor stage and association with a high mortality and recurrence rate (54). Inhibition of CEP192 blocked the proliferation of hepatocellular carcinoma cell lines, suggesting its utility as a novel anti-cancer target (54).…”

“…A study by Liu et al did identify CEP192 as a novel prognostic marker in hepatocellular carcinoma based on increased expression with tumor stage and association with a high mortality and recurrence rate (54). Inhibition of CEP192 blocked the proliferation of hepatocellular carcinoma cell lines, suggesting its utility as a novel anti-cancer target (54). Given these findings, more studies are warranted to determine the role of CEP152 and CEP192 in breast cancer tumorigenesis as well as its potential as a therapeutic target.…”