Abstract 2677: Clinicopathologic significance of CXCR2-CXCL1 signaling in cholangiocarcinoma

Abstract

Abstract 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, cancer-associated fibroblasts (CAF) have been reported to be closely associated with tumor development in various solid carcinomas. We previously reported that chemokine (C-X-C motif) receptor 2 (CXCR2) signaling might play an important role for the pathogenic construction of CAF in the gastric cancer (GC) microenvironment, suggesting that GC cells might alter their adjacent stroma to form a permissive environment for tumor progression, and also we reported that chemokine (C-X-C motif) ligand 1 (CXCL1) from cells stimulated the recruitment of bone marrow cells into GC microenvironment via CXCR2 signaling, resulting in the malignant progression of GC. Following these findings, we reported that among the CXCR2 ligands, CXCL1 might play an important role in the malignant progression of GC via CXCR2 signaling. And then, some studies suggest that CXCR2-CXCL1 plays an important role in not only GC but also other solid cancer. However, there is no report about the clinicopathological significance of CXCR2-CXCL1 signal in cholangiocarcinoma. Then, we examined the clinicopathological significance of CXCR2-CXCL1 signal in cholangiocarcinoma in this study. Patients and Method: We retrospectively analyzed the total cases of 168 patients with cholangiocarcinoma. The expressions of CXCR2 and CXCL1 were investigated by immunohistochemistry, and we then analyzed the correlation between the clinicopathological features of 168 patients and the CXCR2 and CXCL1 expression level. Results: The CXCR2 and CXCL1 positive expression wad as follows: CXCR2 was 18.5% (31/168), CXCL1 was 72.8% (126/173), both CXCR2 and CXCL1 was 17.9% (30/168). Metastasis negative was correlated with CXCL1 expression. Low depth invasion was correlated with CXCR2 expression. The prognoses of the both CXCR2 and CXCL1 positive patients were significantly better than those of CXCR2 and/or CXCL1 negative patients (p<0.023, log rank). Conclusion:CXCLR2 and CXCL1 expression might be a better prognostic factor of patients with cholangiocarcinoma, and CXCR2-CXCL1 signaling might play an important role for tumor-suppressing effects of cholangiocarcinoma. Citation Format: Yurie Yamamoto, Gen Tsujio, Tomohiro Sera, Atsushi Sugimoto, Syuhei Kushiyama, Sadaaki Nishimura, Kenji Kuroda, Ryota Tanaka, Kenjiro Kimura, Ryousuke Amano, Masaichi Ohira, Masakazu Yashiro. Clinicopathologic significance of CXCR2-CXCL1 signaling in cholangiocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2677.