17-beta-hydroxysteroid dehydrogenase 13 inhibits the progression and recurrence of hepatocellular carcinoma
Jun Chen a,b,c, Jian-Yong Zhuo a,b,c, Fan Yang a,b,c, Zhi-Kun Liu a,b,c, Lin Zhou a,b,c, Hai-Yang Xie a,b,c, Xiao Xu a,b,c, Shu-Sen Zheng a,b,c,∗
a Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
b Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
c Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China ∗ Corresponding author at: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
E-mail address: shusenzheng@zju.edu.cn (S.-S. Zheng).
BACKGROUND: Our previous study showed that 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) is down-regulated in hepatocellular carcinoma (HCC). But its function in HCC remains unknown. This study aimed to reveal the function of HSD17B13 and its clinical significance in HCC.
METHODS: mRNA levels of HSD17B13 were analyzed in cohort 1 (30 normal, 30 HBV cirrhosis, 60 HBV-related HCC and 60 peritumoral tissue) by real-time PCR. HSD17B13 protein was evaluated in cohort 2 (15 normal, 33 HBV-cirrhosis, 12 dysplastic nodules, 34 HBV-related HCC, and 9 metastatic HCC) using immunohistochemistry. The association between HSD17B13 and the survival of HCC patients was analyzed in cohort 3 (n?=?88). The inhibitory mechanism of HSD17B13 on HCC was explored .
RESULTS: The mRNA of HSD17B13 and its protein expression were significantly down-regulated in HCC compared to non-tumor specimens (P < 0.001). The sensitivity, specificity and area under curve (AUC) values of HSD17B13 expression levels for HCC detection were 81.7%, 83.7% and 0.856, respectively (P < 0.001). Lower HSD17B13 in peritumoral tissue was an independent risk factor of worse recurrence free survival of HCC patients (HR: 0.41; 95% CI: 0.20-0.83; P = 0.014). The study in Huh 7 and SK-HEP-1 cells showed that HSD17B13 induced an accumulation of cells in G1 phase and reduction of cells in S and G2 phases via up-regulating the expression of P21, P27 and MMP2.
CONCLUSIONS: Lower HSD17B13 in peritumoral tissues was associated with worse recurrence free survival and overall survival of HCC patients. HSD17B13 delayed G1/S progression of HCC cells. HSD17B13 may be a therapeutic target for the treatment of HCC.
2018, Vol. 17 
