1. Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
2. Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
3. Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
4. Present address: Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine; Institute of Medical Genetics, Tongji University, Shanghai, China.
* Hui Lin and Xiaoxiao Fan contributed equally for this work.
Hepatocellular carcinoma (HCC) is the sixth most common tumor worldwide. The relationship between the gene methylation accumulation and HCC has been widely studied. In our study, we used the Sequenom EpiTYPER assay to investigate the methylation levels of the RASA3 in 164 HCC samples and paired adjacent non-cancerous tissues, and the association between methylation level and clinicopathological features. The methylation level of the RASA3 in HCC samples was found significantly lower than that in the adjacent non-cancerous tissues (P<0.0001). Moreover, the hypomethylation of RASA3 in HCC samples was connected with the presence of tumornecrosis (P=0.029) and alcohol intake (P=0.002). Furthermore, it was found that the expression of RASA3 was significantly decreased in tumor tissues (P=0.0053), which was also correlated with the methylation levels of RASA3 gene. Thus, RASA3 hypomethylation is a common feature in HCC, and may be a potential mechanism for HCC development, and serves as a useful biomarker for the early detection, especially in alcohol-associated HCCs.
Keywords: RASA3, Hepatocellular carcinoma, Methylation, clinicopathological factors