Prognostic Value of the FOXK Family Expression in Patients with Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy

Yiyi Zhang; Meifang Xu; Jianhua Chen; Kui Chen; Jinfu Zhuang; Yuanfeng Yang; Xing Liu; Guoxian Guan

doi:10.2147/OTT.S255956

Prognostic Value of the FOXK Family Expression in Patients with Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy

Onco Targets Ther. 2020 Sep 16:13:9185-9201. doi: 10.2147/OTT.S255956. eCollection 2020.

Authors

Yiyi Zhang^#¹, Meifang Xu^#², Jianhua Chen^#³, Kui Chen⁴, Jinfu Zhuang¹, Yuanfeng Yang¹, Xing Liu¹, Guoxian Guan¹

Affiliations

¹ Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.
² Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
³ Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
⁴ Department of General Surgery, The First Hospital of Fuzhou City Affiliated Fujian Medical University, Fuzhou, People's Republic of China.

^# Contributed equally.

Abstract

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: FOXK1; FOXK2; neoadjuvant chemoradiotherapy; prognosis; rectal cancer.

Grants and funding

This study was supported by the Science Foundation of the Fujian Province, (No. 2016J01602; 2019J0105), Special Financial Foundation of Fujian Provincial (No.2015-1297), Young and middle-aged backbone training project in the health system of Fujian province (2016-ZQN-26), the Startup Fund for Scientific Research, Fujian Medical University (2018QH2027, 2018S0130) and Professor Development Foundation of Fujian Medical University (No.JS11006).