npj Precision Oncology (May 2021)

A genomic mutation signature predicts the clinical outcomes of immunotherapy and characterizes immunophenotypes in gastrointestinal cancer

  • Xi Jiao,
  • Xin Wei,
  • Shuang Li,
  • Chang Liu,
  • Huan Chen,
  • Jifang Gong,
  • Jian Li,
  • Xiaotian Zhang,
  • Xicheng Wang,
  • Zhi Peng,
  • Changsong Qi,
  • Zhenghang Wang,
  • Yujiao Wang,
  • Yanni Wang,
  • Na Zhuo,
  • Henghui Zhang,
  • Zhihao Lu,
  • Lin Shen

DOI
https://doi.org/10.1038/s41698-021-00172-5
Journal volume & issue
Vol. 5, no. 1
pp. 1 – 9

Abstract

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Abstract The association between genetic variations and immunotherapy benefit has been widely recognized, while such evidence in gastrointestinal cancer remains limited. We analyzed the genomic profile of 227 immunotherapeutic gastrointestinal cancer patients treated with immunotherapy, from the Memorial Sloan Kettering (MSK) Cancer Center cohort. A gastrointestinal immune prognostic signature (GIPS) was constructed using LASSO Cox regression. Based on this signature, patients were classified into two subgroups with distinctive prognoses (p < 0.001). The prognostic value of the GIPS was consistently validated in the Janjigian and Pender cohort (N = 54) and Peking University Cancer Hospital cohort (N = 92). Multivariate analysis revealed that the GIPS was an independent prognostic biomarker. Notably, the GIPS-high tumor was indicative of a T-cell-inflamed phenotype and immune activation. The findings demonstrated that GIPS was a powerful predictor of immunotherapeutic survival in gastrointestinal cancer and may serve as a potential biomarker guiding immunotherapy treatment decisions.