Upregulation of stromal cell-derived factor 1 alpha expression is: associated with the resistance to neoadjuvant chemoradiotherapy of locally advanced rectal cancer: Angiogenic markers of neoadjuvant chemoradiation

Abstract

The ability to achieve pathologic downstaging after neoadjuvant chemoradiotherapy (NCRT) is correlated with improved survival in locally advanced rectal cancer (LARC). However, there is no effective predictive markers. In this study, the expression of angiogenic markers was evaluated in pretreatment biopsies and corresponding post-treatment resection specimens, and were correlated to histopathological tumour characteristics and response. Fifty-five patients with stage II/III rectal cancer treated with 5-fluorouracil (5-FU)-based NCRT were studied. All patients were administered NCRT followed by surgical resection. Immunohistochemical staining for angiogenic markers [hypoxia-inducible factor in (HIF-1 alpha), vascular endothelial growth factor (VEGF), stromal cell-derived factor 1 alpha (SDF-1 alpha) and placental growth factor (PlGF)] was performed on specimens obtained before NCRT and after surgery. Expression of VEGF, PlGF and HIF-1 alpha protein was downregulated after NCRT in the rectal cancer tissues (P<0.001, P=0.001 and P=0.044, respectively). However, SDF-1 alpha was upregulated after NCRT (P<0.001). Moreover, upregulated expression of SDF-1 alpha (P=0.016) and positive PlGF staining (P=0.001) after NCRT were significantly associated With resistance to NCRT. On multivariate analysis, positive PlGF staining after NCRT was found to be independently associated with resistance to NCRT (P=0.013). Our data suggest that SDF-1 alpha and PlGF should be evaluated as new targets for NCRT in LARC.