TEDC2 plays an oncogenic role and serves as a therapeutic target of hepatocellular carcinoma

• Published in: Digestive and liver disease 2024-05, Vol.56 (5), p.861-871
• Main Authors: Li, Yuhan, Guo, Beichen, Wang, Lewei, Zhou, Feng, Yu, Zhenjun, Huang, Yue, Chen, Rui, Zhang, Mengxia, Zhang, Kun, Zheng, Lina, Jing, Shen, Hong, Wei, Han, Tao
• Format: Article
• Language: English
• Subjects: Biomarker; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Proliferation - genetics; Female; Gene Expression Regulation, Neoplastic; Hepatocellular carcinoma; Humans; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Male; Middle Aged; Prognosis; TEDC2
• ISSN: 1590-8658; 1878-3562
• DOI: 10.1016/j.dld.2023.09.025

Hepatocellular carcinoma (HCC) is one of the most common malignancies and tends to have a poor prognosis due to its insidious onset, difficulty in early diagnosis, and limited treatment options. Tubulin epsilon and delta complex 2 (TEDC2), also known as C16orf59, is implicated in maintaining centriole stability, but the involvement of TEDC2 in HCC remains unknown. This study aimed to investigate the expression profile and potential mechanisms of TEDC2 in HCC. Multiple RNA sequencing datasets were screened for differentially expressed genes in HCC, and the prognosis-related gene, TEDC2, was further screened as a target gene in this study. The expression of TEDC2 in public datasets and clinical specimens was analyzed, and the involvement of TEDC2 in HCC was investigated by bioinformatic analysis and in vitro experiments. TEDC2 levels were elevated in HCC compared to healthy livers. Overexpression of TEDC2 was positively correlated with pathologic stage and histologic grade. In addition, TEDC2 was found to be an independent prognostic predictor. An excellent prognostic model of HCC was successfully constructed with TEDC2 in combination with the TNM stage. Bioinformatic analysis revealed that overexpression of TEDC2 might be associated with impaired tumor immunity in HCC, as evidenced by increased infiltration of T helper 2 (Th2) cells and reduced infiltration of cytotoxic cells. Further studies showed that TP53 mutations regulated TEDC2 expression, and TEDC2 was significantly associated with drug sensitivity. Moreover, overexpression of TEDC2 promoted cell metastasis and proliferation in vitro. These findings initially suggested a crucial effect of TEDC2 overexpression on HCC tumor progression, suggesting its potential as a novel prognostic and therapeutic target in HCC.