The chemokines CXCL9 and CXCL13 as prognostic markers for metastasis and survival in rectal cancer patients after neoadjuvant chemoradiation.

Abstract

627 Background: Distant metastasis is a challenging problem in multimodal treatment of rectal cancer. Valid prognostic markers for the occurrence of metachronous metastasis could help to stratify patients who qualify for adjuvant chemotherapy and intensified follow-up procedures after preoperative chemoradiotherapy (CRT). Methods: We analysed 9 different genes known to prominently figure in crucial pathways of the tumor cell metabolism. mRNA was isolated and quantified from surgical specimens of 77 rectal cancer patients undergoing neoadjuvant CRT. The panel contains genes with relevant function in apoptosis (Birc5, XIAP, SMAC) and epithelial-mesenchymal transitions (SNAI2) as well as the cancer stem-cell marker CD133, the transcription factor ESR1 and the lymphocyte-chemokines CXCL9 and 13. The expression levels in post-CRT rectal cancers were correlated with the development of distant metastasis and with disease-free (DFS) and cancer-specific overall survival (CSS). Results: Intratumoral mRNA expression of the T-cell chemokine CXCL9 (p<0.001) and the B-cell chemokine CXCL13 (p<0.01) was inversely correlated with the occurrence of distant metastasis. Patients with isolated high CXCL9 (p<0.0001) and CXCL13 levels (p<0.01) had a significantly prolonged DFS. Patients with simultaneous expression of CXCL9 and 13 had an excellent DFS compared to patients without expression of any of the chemokines (p<0.0001). Additionally, CXCL9 expression was correlated with an improved CSS (p<0.05). There was no significant correlation between expression levels of the other genes tested and metastasis or survival. Conclusions: The post-CRT expression of the lymphocyte-chemokines CXCL9 and 13 is associated with reduced rates of distant metastases and improved survival in rectal cancers after CRT. Further investigations are needed to prospectively validate these results and characterize the underlying cellular and molecular mechanisms.