The importance of CXCR4 expression in tumor stroma as a potential biomarker in pancreatic cancer

Abstract

Abstract Background. Pancreatic ductal adenocarcinoma (PDAC) is one of the main causes of cancer mortality in the world. A characteristic feature of this cancer is that a large part of the tumor volume is composed of a stroma with different cells and factors. Among these, we can highlight the cytokines, which perform their function through binding to their receptors. Given the impact of the CXCR4 receptor in the interactions between tumor cells and their microenvironment and its involvement in important signaling pathways in cancer, it is proposed as a very promising prognostic biomarker and as a goal for new targeted therapies. Numerous studies analyse the expression of CXCR4 but we suggest focusing on the expression of CXCR4 in the stroma. Methods. Expression of CXCR4 in specimens from 33 patients with PDAC was evaluated by immunohistochemistry techniques and matched with clinicopathological parameters, overall and disease-free survival rates. Results. The percentage of stroma was lower in non-tumor tissue (32.4 ± 5.2) than in tumor pancreatic tissue (67.4 ± 4.8), P-value = 0.001. The level of CXCR4 expression in stromal cells was diminished in non-tumor tissue (8.7 ± 4.6) and higher in tumor pancreatic tissue (23.5 ± 6.1), P-value = 0.022. No significant differences were identified in total cell count and inflamatory cells between non-tumor tissue and pancreatic tumor tissue. No association was observed between CXCR4 expression and any of the clinical or pathological data, overall and disease-free survival rates. Analysing exclusively the stroma of tumor samples, the CXCR4 expression was associated with tumor differentiation, P-value = 0.05. Conclusions. In this study we reflect the importance of CXCR4 expression in the stroma of patients diagnosed with PDAC. In the study of the CXCR4 expression in the stroma we found that more robust results could be generated. Considering the stroma as a component of the tumor mass in this type of cancer, the possible association found between CXCR4 expression in the stroma with tumor differentiation would lead us to propose this receptor as a candidate for the marker with prognostic value or as a possible therapeutic target.