Purpose: To assess the role of the expression levels of FOXK family members, FOXK1 and FOXK2, in predicting response to neo-chemoradiotherapy (NCRT) and prognosis in locally advanced rectal cancer (LARC).
Methods: A total of 256 LARC patients who underwent NCRT and radical resection between 2011 and 2017 were enrolled in the present study. The patients were divided into a training dataset (n=169, 2011– 2015) and a validation dataset (n=87, 2016– 2017). Tumor tissues were collected before NCRT and post-surgery and were used for immunohistochemical analysis.
Results: Oncomine database analysis revealed that FOXK1 and FOXK2 were overexpressed in most cancers especially in colorectal cancer. Additionally, overexpression of FOXK1 and FOXK2 was associated with poorer prognosis by the R2 database. In both our training and validation datasets, the expression of FOXK1 and FOXK2 was lower in the pathological complete response (pCR) group compared with the non-pCR group (P< 0.05). Cox regression analysis demonstrated that pathological N stage (HR=1.810, 95% CI 1.159– 2.827, P=0.009), FOXK1 expression (HR=5.831, 95% CI 2.925– 11.625, P< 0.001), and FOXK2 expression (HR=2.390, 95% CI 11.272– 4.491, P=0.007) were independent predictors of disease-free survival (DFS). Based on the Cox multivariate analysis, we constructed a risk score model that served as a prognostic biomarker and had a powerful ability to predict pCR in LARC patients upon NCRT in both training and validation groups.
Conclusion: Expression levels of FOXK family members were associated with chemoradiotherapy resistance and prognosis of LARC patients following NCRT and were used to construct a risk score model that is a promising biomarker for LARC.
Keywords: rectal cancer, neoadjuvant chemoradiotherapy, FOXK1, FOXK2, prognosis