Identification of MKI67, TPR, and TCHH Mutations as Prognostic Biomarkers for Patients With Defective Mismatch Repair Colon Cancer Stage II/III

BACKGROUND: Stage II/III disease is the most predominant form of colorectal cancer, accounting for approximately 70% of cases. Further, approximately 15%-20% of patients with stage II/III disease have deficient mismatch repair or microsatellite instability-high colorectal cancer. However, there are no identified significant prognostic biomarkers for this disease. OBJECTIVE: This study aimed to identify prognostic markers for patients with deficient mismatch repair/microsatellite instability-high colon cancer stage II/III. DESIGN: Retrospective study design. SETTING: The study was conducted at a high-volume colorectal center, the Cancer Hospital, Chinese Academy of Medical Sciences. PATIENTS: Patients diagnosed with stage II-III deficient mismatch repair/microsatellite instability-high colon cancer who underwent curative surgery at the Cancer Hospital Chinese Academy of Medical Sciences between July 2015 and November 2018. MAIN OUTCOME MEASURES: The primary outcome measure was the influence of differentially mutated genes on progression-free survival. RESULTS: The retrospective deficient mismatch repair/microsatellite instability-high cohort and The Cancer Genome Atlas-microsatellite instability-high cohort involved 32 and 45 patients, respectively. The deficient mismatch repair/microsatellite instability-high patients had higher mutational frequencies of MKI67 , TPR , and TCHH than microsatellite stable patients. MKI67 , TPR , TCHH , and gene combination were significantly correlated with prognosis. The biomarker-mutation-type colon cancer group had a higher risk of recurrence or death than did the wild-type group. Moreover, biomarker-mutation-type tumors had more mutations in the DNA damage repair pathway and tumor mutational burden than did biomarker wild-type tumors. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: MKI67 , TPR , and TCHH may serve as potential diagnostic and prognostic biomarkers for deficient mismatch repair/microsatellite instability-high colon cancer stage II/III