ATG10 overexpression is related to the dismal prognosis and promotes the growth and migration of hepatocellular carcinoma cells via cyclin B1/CDK1 and CDK2

Am J Cancer Res. 2023 Apr 15;13(4):1188-1208. eCollection 2023.

Abstract

Although the expression of autophagy-related 10 (ATG10) is known to be associated with the poor prognosis of cancer patients by enhancing cancer cell growth and migration, the roles of ATG10 in hepatocellular carcinoma (HCC) remains to be determined. In this study, the expression of ATG10 in HCC was analyzed using the data from TCGA databases and was further verified in the clinical samples from our patients. In addition, the relationships of ATG10 expression with clinical features, diagnosis and prognosis, as well as the predictive values of ATG10 expression in overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) were explored. Furthermore, the expression and the prognostic values of ATG10 co-expressed genes were also identified in HCC, which was used to construct prognostic nomograms. Our data showed that the expression level of ATG10 was significantly increased in HCC, and the elevated ATG10 expression was associated with poor prognosis. Moreover, cells with ATG10 knockdown were used to investigate the effects of ATG10 on HCC cell proliferation and migration. We found that silencing ATG10 inhibited the proliferation, migration, and invasion of HCC cells, which was related to the protein expression of cyclin B1, CDK1, and CDK2. Similarly, the overexpression of ATG10 co-expressed genes ATG12, LARS1, CWC27, and SLC30A5 in HCC patients were also associated with the OS, DSS, and PFI. The risk models and nomograms based on ATG10 and ATG10 co-expressed genes indicated the correclation between their expression and the dismal prognosis in HCC patients. In conclusion, ATG10 expression was elevated in HCC and was associated with poor prognosis. Inhibition of ATG10 expression could attenuate cancer progression. ATG10-related nomograms and risk models could be used clinically to evaluate the prognosis of HCC patients.

Keywords: ATG10; hepatocellular carcinoma; nomogram; prognosis; risk model.