Yixin Xu1,2,3, Yuzhe Li3, Ziyan Zhu3, Jing Yang4, Yulin Tan1,2, Yibo Wang5,6, Xuezhong Xu7,8. 1. Department of General Surgery, Wujin Hospital Affiliated With Jiangsu University, Changzhou, Jiangsu, China. 2. The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China. 3. Department of General Surgery, Shanghai General Hospital of Nanjing Medical University, Shanghai, China. 4. Department of Epidemiology and Biostatistics, International Joint Research Center On Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. 5. Department of General Surgery, Wujin Hospital Affiliated With Jiangsu University, Changzhou, Jiangsu, China. wybjll@163.com. 6. The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China. wybjll@163.com. 7. Department of General Surgery, Wujin Hospital Affiliated With Jiangsu University, Changzhou, Jiangsu, China. xxz197001@sina.com. 8. The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China. xxz197001@sina.com.
Abstract
PURPOSE: DNA mismatch repair (MMR) protein deficiency has attached more attention for its potential to be a biomarker of immunotherapy for colorectal cancer (CRC) patients. However, clinical models involving the expression status of MMR protein are rare. Herein, we sought to develop two clinical models (a diagnostic model for the prediction of MMR status and a prognostic model for the prediction of disease-free survival) for CRC patients. METHODS: A total of 582 CRC patients were finally included. There were 53 patients with deficient expression of MMR protein. The differences between the deficient MMR (dMMR) group and the proficient MMR (pMMR) group were analyzed. RESULTS: Compared to pMMR patients, those with dMMR status were younger and had better pathological features (depth of invasion, lymph node metastasis, distant metastasis, pathological stage, perineuronal invasion, and PLT level) and disease-free survival (DFS). The tumor location of the left colon, adenocarcinoma, and abnormal PLT level were identified as the independent predictors for pMMR. Based on these data, we developed the diagnostic model using Logistic regression analysis. It showed a satisfactory accuracy (AUC = 82.3% in the derivate set; AUC = 73.6% in the validation set). Furthermore, pMMR, poorer differentiation, perineuronal invasion, distant metastasis, lower hemoglobin level, and abnormal CEA level were established as the independent prognostic factors of poorer DFS. Based on them, a prognostic model with valuable performance (1-year AUC = 75.5%/3-year AUC = 76.9% in the derivate set; 1-year AUC = 72.3%/3-year AUC = 73.8% in the validation set) was developed. CONCLUSIONS: Our diagnostic and prognostic models could identify CRC patients at risk for pMMR protein expression and disease recurrence. It may contribute to improving the diagnosis and treatment of CRC patients at an individual level.
PURPOSE: DNA mismatch repair (MMR) protein deficiency has attached more attention for its potential to be a biomarker of immunotherapy for colorectal cancer (CRC) patients. However, clinical models involving the expression status of MMR protein are rare. Herein, we sought to develop two clinical models (a diagnostic model for the prediction of MMR status and a prognostic model for the prediction of disease-free survival) for CRC patients. METHODS: A total of 582 CRC patients were finally included. There were 53 patients with deficient expression of MMR protein. The differences between the deficient MMR (dMMR) group and the proficient MMR (pMMR) group were analyzed. RESULTS: Compared to pMMR patients, those with dMMR status were younger and had better pathological features (depth of invasion, lymph node metastasis, distant metastasis, pathological stage, perineuronal invasion, and PLT level) and disease-free survival (DFS). The tumor location of the left colon, adenocarcinoma, and abnormal PLT level were identified as the independent predictors for pMMR. Based on these data, we developed the diagnostic model using Logistic regression analysis. It showed a satisfactory accuracy (AUC = 82.3% in the derivate set; AUC = 73.6% in the validation set). Furthermore, pMMR, poorer differentiation, perineuronal invasion, distant metastasis, lower hemoglobin level, and abnormal CEA level were established as the independent prognostic factors of poorer DFS. Based on them, a prognostic model with valuable performance (1-year AUC = 75.5%/3-year AUC = 76.9% in the derivate set; 1-year AUC = 72.3%/3-year AUC = 73.8% in the validation set) was developed. CONCLUSIONS: Our diagnostic and prognostic models could identify CRC patients at risk for pMMR protein expression and disease recurrence. It may contribute to improving the diagnosis and treatment of CRC patients at an individual level.
Authors: Thierry André; Kai-Keen Shiu; Tae Won Kim; Benny Vittrup Jensen; Lars Henrik Jensen; Cornelis Punt; Denis Smith; Rocio Garcia-Carbonero; Manuel Benavides; Peter Gibbs; Christelle de la Fouchardiere; Fernando Rivera; Elena Elez; Johanna Bendell; Dung T Le; Takayuki Yoshino; Eric Van Cutsem; Ping Yang; Mohammed Z H Farooqui; Patricia Marinello; Luis A Diaz Journal: N Engl J Med Date: 2020-12-03 Impact factor: 91.245