Hypoxia-Inducible Factor 1 Predicts Pathological Complete Response and Survival for Locally Advanced Rectal Cancer Patients after Preoperative Chemoradiotherapy

Objective: Preoperative chemoradiotherapy (CRT) is a standard option for patients with advanced rectal cancer (RC) located in the lower part of the rectum. Besides, some early stage RC patients may be over-treated, due to imprecise preoperative staging. The aim this study was to explore the value of hypoxia-inducible factor 1 alpha (HIF-1 alpha) as a predictor of benefit from preoperative CRT for locally advanced RC patients in terms of pathologic complete response (pCR) and clinical outcomes.Methods: Colonoscopic biopsy specimens from 114 RC patients were subjected to immunohistochemistry method for analysis of HIF-1 alpha expression, followed by analyzing clinicopathological characteristics. Independent factors associated with pCR were analyzed using univariate and logistic multivariate regression. Cox proportional hazard models were utilized to analyze param-eters independently related to overall survival (OS) and recurrence-free survival (RFS) of RC patients.Results: HIF-1 alpha was observed to be highly expressed in 52.6% patients (60/114). Tumor size was significantly larger in the HIF-1 alpha high expression group than in the low expression group (p = 0.027). The proportion of patients who achieved pCR in the high expression group, was significantly lower than the low expression group (p = 0.001). Besides, HIF-1 alpha was identified as the only predictor of pCR in the multivariate regression analysis (p = 0.006). In terms of prognosis, the 3-year RFS rate and OS rate were significantly lower in the high-expression HIF-1 alpha group than those in the low-expression HIF-1 alpha group (p = 0.015 & p = 0.027). HIF-1 alpha level was significantly related to RFS and OS based on univariate and multivariate analyses.Conclusions: HIF-1 alpha expression is a potential predictor for pCR and an independent prognostic factor for RC patients with preoperative CRT.