CXCR2 signaling might have a tumor-suppressive role in patients with cholangiocarcinoma
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Yurie Yamamoto1,2, Atsushi Sugimoto1,2,3, Koji Maruo1,2,3
1Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan.
Background:
We reported that chemokine C-X-C motif receptor 2 (CXCR2) signaling appears to play an important role in the pathogenic signaling of gastric cancer (GC), and although CXCR2 may have a role in other solid cancers, the significance of CXCR2 in cholangiocarcinoma (CCA) has not been evaluated. Herein, we determined the clinicopathologic significance of CXCL1-CXCR2 signaling in CCA.
Materials And Methods:
Two human CCA cell lines, OCUG-1 and HuCCT1, were used. CXCR2 expression was examined by western blotting. We investigated the effects of CXCL1 on the proliferation (by MTT assay) and migration activity (by a wound-healing assay) of each cell line. Our immunohistochemical study of the cases of 178 CCA patients examined the expression levels of CXCR2 and CXCL1, and we analyzed the relationship between these expression levels and the patients' clinicopathologic features.
Results:
CXCR2 was expressed on both CCA cell lines. CXCL1 significantly inhibited both the proliferative activity and migratory activity of both cell lines. CXCL1 and CXCR2 were immunohistochemically expressed in 73% and 18% of the CCA cases, respectively. The CXCL1-positive group was significantly associated with negative lymph node metastasis (p = 0.043). The CXCR2-positive group showed significantly better survival (p = 0.042, Kaplan-Meier). A multivariate logistic regression analysis revealed that CXCR2 expression (p = 0.031) and lymph node metastasis (p = 0.004) were significantly correlated with the CCA patients' overall survival.
Conclusion:
CXCR2 signaling might exert a tumor-suppressive effect on CCA cells. CXCR2 might be a useful independent prognostic marker for CCA patients after surgical resection.
Insights
Chemokine receptor CXCR2 signaling may suppress cholangiocarcinoma (CCA) growth. CXCR2 expression is a potential prognostic marker for CCA patients, indicating better survival after surgery.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Chemokine receptor CXCR2 (CXCR2) signaling is implicated in gastric cancer pathogenesis.
- The role of CXCR2 in cholangiocarcinoma (CCA) remains unevaluated.
- This study investigates the clinicopathologic significance of CXCL1-CXCR2 signaling in CCA.
Purpose of the Study:
- To determine the clinicopathologic significance of CXCL1-CXCR2 signaling in cholangiocarcinoma (CCA).
- To evaluate the prognostic value of CXCR2 expression in CCA patients.
Main Methods:
- Utilized human CCA cell lines (OCUG-1, HuCCT1) to assess CXCR2 expression and CXCL1 effects on proliferation and migration.
- Conducted immunohistochemical analysis on 178 CCA patient samples to correlate CXCL1 and CXCR2 expression with clinicopathologic features.
- Performed western blotting, MTT assays, wound-healing assays, Kaplan-Meier survival analysis, and multivariate logistic regression.
Main Results:
- CXCL1 inhibited proliferation and migration in CCA cell lines.
- CXCL1 and CXCR2 were expressed in 73% and 18% of CCA cases, respectively.
- CXCL1 positivity correlated with reduced lymph node metastasis. CXCR2 positivity was linked to significantly better patient survival. Multivariate analysis confirmed CXCR2 expression and lymph node metastasis as independent prognostic factors for overall survival.
Conclusions:
- CXCR2 signaling may exert a tumor-suppressive effect in CCA.
- CXCR2 represents a potential independent prognostic biomarker for CCA patients undergoing surgical resection.
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