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TET1 mutations as a predictive biomarker for immune checkpoint inhibitors in colon adenocarcinoma

Tianzhu Qiu1, Xiaoxuan Wang2, Furong Du2

  • 1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.

World Journal of Surgical Oncology
|April 9, 2022
PubMed
Abstract

Insights

Ten-eleven translocation 1 (TET1) mutations are linked to better outcomes for colon cancer patients treated with immune checkpoint inhibitors (ICIs). TET1 mutations may predict response to ICIs in colon adenocarcinoma (COAD).

Area of Science:

  • Oncology
  • Genetics
  • Immunotherapy

Background:

  • Ten-eleven translocation 1 (TET1) is crucial for DNA demethylation and implicated in colorectal cancer pathogenesis.
  • TET1 mutations correlate with improved responses to immune checkpoint inhibitors (ICIs) in various cancers.
  • The role of TET1 mutations in ICI response specifically within colon cancer remains under-investigated.

Purpose of the Study:

  • To investigate the association between TET1 mutations and clinical outcomes in colon adenocarcinoma (COAD) patients receiving ICIs.
  • To identify potential predictive biomarkers for ICI therapy response in COAD.

Main Methods:

  • Comparative analysis of prognosis, immune characteristics, and DNA damage repair (DDR) pathway mutations between TET1-mutated and wild-type COAD patients.
  • Assessment of tumor mutational burden, neoantigen load, immune cell infiltration, and gene expression.
  • Evaluation of drug sensitivity profiles for TET1-mutated versus wild-type groups.

Main Results:

  • Patients with TET1 mutations exhibited significantly longer overall survival in the ICI-treated cohort (p = 0.0059).
  • TET1-mutated COAD patients displayed higher tumor mutational burden, neoantigen load, immune cell infiltration, and DDR pathway mutations.
  • Increased expression of immune-related genes and heightened sensitivity to lapatinib and 5-fluorouracil were observed in TET1-mutated patients.

Conclusions:

  • TET1 mutations are associated with favorable clinical outcomes and enhanced anti-tumor immunity in COAD patients treated with ICIs.
  • TET1 mutations represent a promising predictive biomarker for ICI therapy efficacy in colon cancer.
Keywords:
Colon adenocarcinomaImmune checkpoint inhibitorsOverall survivalPredictive biomarkerTen-eleven translocation 1

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