DOI: 10.1097/dcr.0000000000002734 ISSN:

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

Jingfang Lv, Wenbin Li, Xintong Wang, Lei Guo, Dongliang Wang, Yiran Zhang, Jun Yu, Tianli Chen, Beifang Niu, Xishan Wang, Zheng Liu
  • Gastroenterology
  • General Medicine

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

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