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

Abstract

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 1α (HIF-1α) 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-1α 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 parameters independently related to overall survival (OS) and recurrence-free survival (RFS) of RC patients. Results: HIF-1α was observed to be highly expressed in 52.6% patients (60/114). Tumor size was significantly larger in the HIF-1α 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-1α 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-1α group than those in the low-expression HIF-1α group (p = 0.015 & p = 0.027). HIF-1α level was significantly related to RFS and OS based on univariate and multivariate analyses. Conclusions: HIF-1α expression is a potential predictor for pCR and an independent prognostic factor for RC patients with preoperative CRT.