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Development of novel models for predicting mismatch repair protein deficiency and relevant disease-free survival in colorectal cancer patients

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International Journal of Colorectal Disease Aims and scope Submit manuscript

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.

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Data availability statement

The original contributions presented in this study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

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Acknowledgements

We appreciate Pro. Liu (Nanjing Medical University) and Qing Chen (Nanjing Medical University) for their help in this study. This study was sponsored by the Medical Research Project of Jiangsu Health Commission (Z2021010), the Changzhou Sci&Tech Program (CJ20210017 and CJ20210013), and the Clinical Technology Development Foundation of Jiangsu University (JLY2021022).

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Authors and Affiliations

  1. Department of General Surgery, Wujin Hospital Affiliated With Jiangsu University, Changzhou, Jiangsu, China

    Yixin Xu, Yulin Tan, Yibo Wang & Xuezhong Xu

  2. The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China

    Yixin Xu, Yulin Tan, Yibo Wang & Xuezhong Xu

  3. Department of General Surgery, Shanghai General Hospital of Nanjing Medical University, Shanghai, China

    Yixin Xu, Yuzhe Li & Ziyan Zhu

  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

    Jing Yang

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  1. Yixin Xu
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  5. Yulin Tan
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Contributions

Yixin Xu conceived and designed the study and wrote the manuscript. Yuzhe Li collected the original data. Jing Yang and Ziyan Zhu analyzed the data. Yixin Xu and Yulin Tan designed and edited the figures and tables. Yibo Wang and Xuezhong Xu reviewed and edited the manuscript. All authors agree to be accountable for the content of this work. All authors contribute to the article and approved the submitted version.

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Correspondence to Yibo Wang or Xuezhong Xu.

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Our study was approved by the ethics committee of Wujin Hospital. Written informed consent was obtained from the patients including in the present study.

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The authors declare no competing interests.

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Xu, Y., Li, Y., Zhu, Z. et al. Development of novel models for predicting mismatch repair protein deficiency and relevant disease-free survival in colorectal cancer patients. Int J Colorectal Dis 37, 1449–1464 (2022). https://doi.org/10.1007/s00384-022-04150-6

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