The clinicopathological significance of Thrombospondin-4 expression in the tumor microenvironment of gastric cancer

Autoři: Kenji Kuroda aff001;  Masakazu Yashiro aff001;  Tomohiro Sera aff001;  Yurie Yamamoto aff002;  Yukako Kushitani aff001;  Atsushi Sugimoto aff001;  Syuhei Kushiyama aff001;  Sadaaki Nishimura aff001;  Shingo Togano aff001;  Tomohisa Okuno aff001;  Tatsuro Tamura aff001;  Takahiro Toyokawa aff001;  Hiroaki Tanaka aff001;  Kazuya Muguruma aff001;  Masaichi Ohira aff001
Působiště autorů: Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka city, Japan aff001;  Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka city, Japan aff002;  Cancer Center for Translational Research, Osaka City University Graduate School of Medicine, Osaka city, Japan aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224727



Thrombospondin-4 [1] is an extracellular glycoprotein involved in wound healing and tissue remodeling. Although THBS4 is reportedly frequently expressed in solid tumors, there are few reports of the clinicopathological features of carcinomas with THBS4 expression. We evaluated the clinicopathologic significance of THBS4 expression in gastric carcinoma (GC).

Materials and methods

We retrospectively analyzed the cases of 584 GC patients. The expression of THBS4 in each tumor was evaluated by immunohistochemistry. We then divided the patients into the THBS4-high (n = 223, 38.2%) group and THBS4-low (n = 361, 61.8%) group. THBS4 expression in cancer-associated fibroblasts (CAFs), normal-associated fibroblasts (NFs) and gastric cancer cell lines was examined by western blotting.


THBS4 is expressed on stromal cells with αSMA or Podoplanin expression in the GC microenvironment, but not expressed on cancer cells with cytokeratin expression. The western blot analysis results showed that CAFs (but not NFs and cancer cells) expressed THBS4. Compared to the THBS4-low expression status, the THBS4-high expression status was correlated with higher αSMA expression, higher invasion depth, lymph-node metastasis, lymphatic invasion, peritoneal cytology, peritoneal metastasis, larger tumor size, microscopic diffuse type, and the macroscopic diffuse infiltrating type. The THBS4-high group's 5-year overall survival rate was significantly poorer than that of the THBS4-low group. A multivariate analysis revealed that THBS4 expression was an independent prognostic factor.


THBS4 is expressed on CAFs in the gastric cancer microenvironment. THBS4 from CAFs is associated with the metastasis of cancer cells, and is a useful prognostic indicator for gastric cancer patients.

Klíčová slova:

Carcinomas – Fibroblast growth factor – Fibroblasts – Gastric cancer – Metastasis – Prognosis – Stromal cells


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Článek vyšel v časopise


2019 Číslo 11