Identification of CCDC115 as an adverse prognostic biomarker in liver cancer based on bioinformatics and experimental analyses

Abstract

Liver hepatocellular carcinoma (LIHC) is a major malignant tumor of the digestive system with a high incidence rate and poor early diagnosis. Coiled-coil domain-containing protein 115 (CCDC115), an accessory component of vacuolar-ATPase with dramatically abnormal expression, is associated with survival outcomes of cancer patients. However, the role of CCDC115 in LIHC remains unclear. In this study, we aimed to determine the functional role of CCDC115 in LIHC by examining CCDC115 expression, and its influence on LIHC prognosis. Through extensive statistical analyses, using LIHC patient databases, we observed that CCDC115 expression significantly increased in tumor tissues of LIHC patients. In addition, CCDC115 expression correlated with the poor prognosis. Additionally, CCDC115 was found to be involved in several cancer-related pathways, specifically the PI3K-Akt pathway. The expression of CCDC115 was positively correlated with human leukocyte antigen molecules as well as with immune checkpoint molecules in LIHC patients. We performed in vitro experiments and confirmed that the expression of CCDC115 significantly affects the proliferation potential, metastasis and sorafenib resistance of liver cancer cells, as well as some key protein expression in PI3K-Akt pathway. These results indicate that CCDC115 could serve as a diagnostic and prognostic biomarker of LIHC, and targeting CCDC115 may provide a potential strategy to enhance the efficacy of liver cancer therapy.

Keywords

• CCDC115
• Hepatocellular carcinoma
• Prognosis
• PI3K-Akt pathway
• Drug resistance