Prognostic impact of carbohydrate sulfotransferase 15 in patients with pancreatic ductal adenocarcinoma

Abstract

Patients with pancreatic ductal adenocarcinoma (PDA) typically succumb to mortality early, even following surgical resection. Therefore, prognostic factors associated with early mortality are required to improve the survival of patients with PDA following surgical resection. Carbohydrate sulfotransferase 15 (CHST15) is responsible for the biosynthesis of sulfated chondroitin sulfate E (CS-E), which serves a pivotal function in cancer progression by cleaving CD44. CHST15 and CD44 expression in PDA tissue were assessed as a prognostic factor in patients with PDA following surgical resection. A total of 36 consecutive patients with PDA were enrolled following surgical resection between January 2008 and December 2014. The intensities of CHST15 and CD44 expression were analyzed by immunohistochemical staining. The recurrence period was significantly earlier in the strong CHST15 expression group compared with the negative-to-moderate CHST15 expression group. Overall survival (OS) was also significantly decreased in the strong CHST15 expression group compared with the negative-to-moderate CHST15 expression group. Multivariate analysis also indicated significant associations between CHST15 overexpression and disease-free survival (DFS) and OS. However, expression of CD44 in PDA tissue was not associated with DFS or OS. The present study has demonstrated for the first time that high CHST15 expression in PDA tissue may represent a potential predictive marker of DFS and OS in patients with PDA following surgical resection.

Long noncoding RNA HOTAIR promotes invasion of breast cancer cells through chondroitin sulfotransferase CHST15

“…Elevated CHST15 expression was associated with poor disease-free survival and overall survival in patients with pancreatic adenocarcinoma (PDA). 32 Consistently, downregulation of CHST15 resulted in proliferation inhibition in vitro and in xenograft animal models of PDA. 33 While these results indicate that CHST15 plays an important role in cancer cell growth, its function in breast cancer is not clear.…”

“…The molecular mechanisms of CHST15 and its family members in cancer biology are largely unexplored, but emerging evidence suggests crucial functions of these enzymes in cancer development as well as progression. Elevated CHST15 expression was associated with poor disease‐free survival and overall survival in patients with pancreatic adenocarcinoma (PDA) . Consistently, downregulation of CHST15 resulted in proliferation inhibition in vitro and in xenograft animal models of PDA .…”

Clinical Potential of Oligonucleotide Therapeutics against Pancreatic Cancer

“…It was reported that glycosaminoglycan, a cancer stromal molecule, is involved in various cancer developmental phases, such as proliferation, invasion, metastasis and angiogenesis[4,[58][59][60]. Specifically, it was found that chondroitin sulfate-E (CS-E), a matrix glycosaminoglycan, was expressed in both the tumor cells and stromal cells surrounding the tumor in pancreatic cancer patient tissues[59,61].In accord with the above evidence, we previously demonstrated that high CHST15 expression, which is responsible for the biosynthesis of sulfated CS-E, may represent a potential predictive marker of OS in patients with pancreatic cancer following surgical resection[62] and that STNM01, a CHST15 siRNA, successfully inhibited pancreatic tumor growth in xenograft experiments by using the RNAi strategy, as shown inFigure 2…”

Endoscopic Ultrasound‑Guided Antitumor Therapy for Advanced Pancreatic Cancer

“…[6] Carbohydrate sulfotransferase 15 (CHST15) and its specific product chondroitin sulfate-E have been shown to be associated with poor prognosis in many cancers including pancreatic cancers. [7,8] Suppression of CHST15 by siRNA has been shown to inhibit tumor growth in mice. [7,8] Thus, CHST15 is a novel therapeutic target that regulates the tumor microenvironment in pancreatic cancer.…”