OncoTargets and Therapy (Apr 2021)
Construction of the Prediction Model for Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy Based on Pretreatment Tumor-Infiltrating Macrophage-Associated Biomarkers
Abstract
Xing Liu,1 Shuping Zheng,2 Yong Peng,3 Jinfu Zhuang,4 Yuanfeng Yang,4 Yunlu Xu,2 Guoxian Guan1 1Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 2Public Technology Service Center, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of General Surgery, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of ChinaCorrespondence: Guoxian GuanDepartment of Colorectal Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, Fujian, People’s Republic of ChinaTel +86 591-83357896Email [email protected] XuPublic Technology Service Center, Fujian Medical University, 1 Xuefubei Road, Fuzhou City, 350001, Fujian, People’s Republic of ChinaTel +86 591-22862408Email [email protected]: 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: rectal cancer, neoadjuvant chemoradiotherapy, risk, prognosis
