Abstract
Carbohydrate sulfotransferase 4 (CHST4) plays an important role in lymphocyte homing and is abnormally expressed in several cancer types; however, its precise function in tumor development and progression is unknown. Here we confirm that CHST4 is aberrantly expressed in various tumor subtypes. In particular, we found that CHST4 expression was downregulated in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) tumors compared to paired normal tissue. We also showed that CHST4 overexpression inhibited the proliferation and metastasis of HCC cells in vitro. Clinically, CHST4 was identified as an independent prognostic factor for HBV-HCC patients. We further illuminated the anti-tumor role and mechanism of CHST4 in HBV-HCC by constructing a FENDRR–miR-10b-5p–CHST4 competing endogenous RNA network. We found that downregulation of CHST4 expression may promote HBV expression and regulate ribonucleoprotein complex biogenesis to promote malignant behaviors in HBV-HCC. CHST4 may also recruit CD4+ T cells, macrophages, dendritic cells, and neutrophils into the tumor microenvironment to inhibit the progression of HBV-HCC. Overall, our findings suggest that CHST4 acts as a tumor suppressor in HCC-HBV and represents a potential diagnostic and therapeutic target.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer deaths worldwide [1,2,3]
In terms of protein expression (Figure 1C and Supplementary Figure S2A), low levels of Carbohydrate sulfotransferase 4 (CHST4) were observed in intestinal epithelial cells, and strong expression was found in goblet cells
We found that CHST4 expression was lower in tumor tissues than in normal tissues, and hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) patients with high CHST4 expression had longer overall survival (OS) and disease-free survival (DFS)
Summary
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer deaths worldwide [1,2,3]. There has been considerable progress in the treatment of HCC, patient prognosis remains bleak [4]. Chronic hepatitis B virus (HBV) infection is a major risk factor for HCC [5] and is responsible for about 50% of HCC cases and almost all childhood liver cancer [6]. In China, most HCC is related to HBV infection [7,8,9]. CHST4 and Cancer Prognosis have been used to monitor at-risk populations, such as alphafetoprotein L3 (AFP-L3), des gamma carboxyprothrombin (DCP), glypican 3 (GPC3), and Golgi membrane protein 73 (GP73), yet these serum markers are not elevated in all HCC subtypes [10, 11]. Effective and reliable biomarkers for the early detection of HCC are in high demand
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