Overexpression of carbohydrate sulfotransferase 15 in pancreatic cancer stroma is associated with worse prognosis

Matsuda,Yoko; Fujii,Yuko; Matsukawa,Miho; Ishiwata,Toshiyuki; Nishimura,Makoto; Arai,Tomio

doi:10.3892/ol.2019.10764

Overexpression of carbohydrate sulfotransferase 15 in pancreatic cancer stroma is associated with worse prognosis

Authors:
- Yoko Matsuda
- Yuko Fujii
- Miho Matsukawa
- Toshiyuki Ishiwata
- Makoto Nishimura
- Tomio Arai
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Affiliations: Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Itabashi, Tokyo 173‑0015, Japan, Department of Endoscopy, Tokyo Metropolitan Geriatric Hospital, Itabashi, Tokyo 173‑0015, Japan, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Itabashi, Tokyo 173‑0015, Japan
Published online on: August 16, 2019 https://doi.org/10.3892/ol.2019.10764
Pages: 4100-4105
Copyright: © Matsuda et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Carbohydrate sulfotransferase 15 (CHST15) synthesizes matrix proteoglycan that regulates various pathogenic mediators and contributes to tissue remodeling and fibrosis during injury. CHST15 has been reported to promote tumor growth and invasion in various types of cancer. Our previous study reported the safety and efficacy of EUS‑guided fine‑needle injection (EUS‑FNI) of STNM01, a double‑stranded RNA oligonucleotide that specifically represses CHST15, for use in patients with pancreatic cancer. The present study aimed to determine the expression and clinicopathological characteristics of CHST15 in pancreatic cancer. Immunohistochemical staining was performed for CHST15 using pancreatic tissues from 64 patients (28 males and 36 females; age, 69.0±9.6 years) with pancreatic cancer who underwent surgery. For the evaluation of fibrosis, two categories were defined (mature and immature), based on the existence of collagen, myxoid stroma and fibroblasts, using hematoxylin and eosin specimens. The positive percentage of CHST15 was quantified, patients were divided into two groups according to high and low CHST15 expression in both the cancer and stroma tissues, and the association between CHST15 expression in cancer cells and the stroma was analyzed. Additionally, the present study analyzed the association between CHST15 expression and clinicopathological information, including overall and disease‑free survival. The expression levels of CHST15 were detected in the cytoplasm of pancreatic cancer cells and fibroblasts in the cancer stroma. CHST15 expression in cancer cells was not identified to be associated with overall survival (P=0.52). However, patients with high CHST15 expression in the stroma exhibited worse overall survival compared with patients with low CHST15 expression (P=0.02). CHST15 expression in the stroma exhibited a positive association with that in cancer cells (P=0.01). High CHST15 expression in the stroma group was associated with a higher incidence of immature fibrosis (P=0.02) compared with mature fibrosis. CHST15 expression in cancer cells was associated with Union for International Cancer Control stage (P=0.02) and invasive front. Age and sex were not associated with CHST15 expression. The present study revealed that overexpression of CHST15 in stroma was associated with worse overall survival and immature fibrosis. Overexpression of CHST15 in cancer cells was associated with tumor stage. These results suggested that targeting therapy for CHST15 may be useful for stroma fibroblasts and cancer cells.

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