Construction of the Prediction Model for Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy Based on Pretreatment Tumor-Infiltrating Macrophage-Associated Biomarkers

Xing Liu; Shuping Zheng; Yong Peng; Jinfu Zhuang; Yuanfeng Yang; Yunlu Xu; Guoxian Guan

doi:10.2147/OTT.S297263

Construction of the Prediction Model for Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy Based on Pretreatment Tumor-Infiltrating Macrophage-Associated Biomarkers

Onco Targets Ther. 2021 Apr 13:14:2599-2610. doi: 10.2147/OTT.S297263. eCollection 2021.

Authors

Xing Liu¹, Shuping Zheng², Yong Peng³, Jinfu Zhuang⁴, Yuanfeng Yang⁴, Yunlu Xu², Guoxian Guan¹

Affiliations

¹ Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, People's Republic of China.
² Public Technology Service Center, Fujian Medical University, Fuzhou, People's Republic of China.
³ Department of General Surgery, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
⁴ Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.

Abstract

Purpose: To assess the value of macrophage-related biomarkers (CD163, CD68, MCSF, and CCL2) for predicting the response to neo-chemoradiotherapy (NCRT) and the prognosis of locally advanced rectal cancer (LARC).

Methods: We enrolled 191 patients who underwent neoadjuvant chemoradiotherapy and radical resection between 2011 and 2015. Tumor tissues were collected before NCRT with a colonoscope and post-surgery and were subjected to immunohistochemical analysis.

Results: The expression levels of macrophage-related biomarkers (CD163, CD68, MCSF, and CCL2) were lower in the pathological complete response (pCR) group when compared with the non-pCR group (all P<0.05). Based on X-tile plots, we divided the tumors in two groups and found that lower pre-NCRT/post-surgical CD163, CD68, MCSF, CCL2 scores correlated with improved DFS. Cox regression analysis demonstrated that pre-NCRT CD163 (HR=1.008, 95% CI 1.003-1.013, P=0.003) and MCSF (HR=2.187, 95% CI 1.343-3.564, P=0.002) scores were independent predictors of DFS. Based on Cox multivariate analysis, we constructed a risk score model with a powerful ability to predict pCR in LARC patients. Moreover, COX regression analysis was performed to explore the role of the risk score in LARC patients. The results demonstrated that tumor size (HR=1.291, P=0.041), worse pathological TNM stage (HR=1.789, P=0.005, and higher risk score (HR=1.084, P<0.001) were significantly associated with impaired disease-free survival. Based on the above results, a nomogram and decision curve analysis were generated.

Conclusion: The expression levels of macrophage-related biomarkers CD163, CD68, MCSF, and CCL2 were associated with chemoradiotherapy resistance and prognosis in LARC patients following NCRT. A risk score model was constructed which could be used to predict LARC outcome.

Keywords: neoadjuvant chemoradiotherapy; prognosis; rectal cancer; risk.

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. 2020B019; No. 2015-1297), Young and middle-aged backbone training project in the health system of Fujian province (2015-ZQN-JC-17; 2016-ZQN-26), the Startup Fund for Scientific Research, Fujian Medical University (2018QH2027) and Professor Development Foundation of Fujian Medical University (No. JS11006).