Abstract 6193: The clinicopathologic significance of the CXCR2 ligands, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8 in gastric cancer
Authors: Yamamoto Yurie , Kuroda Kenji , Sera Tomohiro , Sugimoto Atsushi , Kushiyama Syuhei , Nishimura Sadaaki , Togano Shingo , Okuno Tomohisa , Yoshii Mami , Tamura Tatsuro , Toyokawa Takahiro , Tanaka Hiroaki , Muguruma Kazuya , Ohira Masaichi , Yashiro Masakazu 
Published: September 2020

Background: Cancer progression has been recognized as not only the proliferation of tumor cells but also an interaction between cancer cells and the surrounding stroma in the tumor microenvironment. Among the tumor stromal cells, fibroblasts (especially cancer-associated fibroblasts) have been reported to be closely associated with tumor development in various solid carcinomas. We reported that chemokine (C-X-C motif) receptor 2 (CXCR2) signaling might play an important role in the pathogenic construction of tumor fibroblasts in the gastric tumor microenvironment, suggesting that gastric cancer cells might alter their adjacent stroma to form a permissive environment for tumor progression. Following those findings, we reported that chemokine (C-X-C motif) ligand 1 (CXCL1) from cells stimulated the recruitment of bone marrow cells into the gastric cancer (GC) microenvironment via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling, resulting in the malignant progression of GC. The reported CXCR2 ligands are not only CXCL1 but also CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8. However, there has been only a single in vitro study of significance of these CXCR2 ligands in GC. We thus examined the clinicopathological significance of these members of the CXCL family in GC.

Method: We retrospectively analyzed the cases of 590 GC patients. The expressions of CXCR2 ligands were investigated by immunohistochemistry, and we then analyzed the correlation between the clinicopathological features of the patients and the expressions of CXCR2 ligands.

Result: The expressions were as follows: CXCL1, 46.2% (257/557); CXCL2, 20.7% (122/590); CXCL3, 17.1% (101/589); CXCL5/CXCL6, 2.9% (17/589); CXCL7, 36.4% (215/590); and CXCL8 1.7% (10/585) of the cases. High invasion depth was correlated with CXCL1 expression. Lymph node metastasis was correlated with high expressions of CXCL1 and CXCL7. Lymphatic invasion and venous invasion were correlated with CXCL1 and CXCL7 expression. Peritoneal cytology positivity was correlated with high expressions of CXCL1 and CXCL7. The prognoses of the CXCL1-positive patients were significantly poorer than those of the CXCL1-negative patients (p&lt;0.001, log-rank).

Conclusion: Among the CXCR2 ligands, CXCL1 and CXCL7 were frequently expressed in GC cells. CXCL1 was closely associated with malignant potential of GC and was an independent prognostic factor. CXCL1 might play an important role in the malignant progression of GC via CXCL1/CXCR2 signaling.

Citation Format: Yurie Yamamoto, Kenji Kuroda, Tomohiro Sera, Atsushi Sugimoto, Syuhei Kushiyama, Sadaaki Nishimura, Shingo Togano, Tomohisa Okuno, Mami Yoshii, Tatsuro Tamura, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Masakazu Yashiro. The clinicopathologic significance of the CXCR2 ligands, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8 in gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6193.