Chromosomal Instability May Not Be a Predictor for Immune Checkpoint Inhibitors from a Comprehensive Bioinformatics Analysis

Life

Yi-Ru Pan¹  Chun-Nan Yeh¹  Ming-Huang Chen²  Jen-Shi Chen³  Chiao-En Wu³  Wen-Kuan Huang³  JohnWen-Cheng Chang³  Da-Wei Yeh⁴  Yu-Chao Wang⁴ 

[1] Department of General Surgery and Liver Research Center, Chang Gung Memorial Hospital, Linkou branch, Chang Gung University, Taoyuan 333, Taiwan;Department of Oncology, Taipei Veterans General Hospital, Taipei 112, Taiwan;Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan;Institute of Biomedical Informatics, National Yang-Ming University, Taipei 112, Taiwan;

关键词: CIN70;    chromosomal instability;    immunotherapy;    immune checkpoint inhibitors;    tumor mutation burden;    microsatellite instability;   

DOI  :  10.3390/life10110276

来源: DOAJ

【 摘 要 】

Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although their predictive tools have not yet completely developed. Here, we aimed to exam the role of 70-gene chromosomal instability signature (CIN70) in cancers, and its association with previous predictors, tumor mutation burden (TMB), and microsatellite instability (MSI), for patients undergoing ICIs, as well as the possible predictive value for ICIs. We examined the association of CIN70 with TMB and MSI, as well as the impact of these biomarkers on the survival of 33 cancer cohorts from The Cancer Genome Atlas (TCGA) databank. The predictive value of the ICIs of CIN70 in previously published reports was also validated. Using the TCGA dataset, CIN70 scores were frequently (either positively or negatively) associated with TMB, but were only significantly associated with MSI status in three types of cancer. In addition, our current study showed that all TMB, MSI, and CIN70 had their own prognostic values for survival in patients with various cancers, and that they could be cancer type-specific. In two validation cohorts (melanoma by Hugo et al. and urothelial cancer by Snyder et al.), no significant difference of CIN70 scores was found between responders and non-responders (p-value = 0.226 and 0.108, respectively). In addition, no overall survival difference was noted between patients with a high CIN70 and those with a low CIN70 (p-value = 0.106 and 0.222, respectively). In conclusion, the current study, through a comprehensive bioinformatics analysis, demonstrated a correlation between CIN70 and TMB, but CIN70 is not the predictor for cancer patients undergoing ICIs. Future prospective studies are warranted to validate these findings.

【 授权许可】

Unknown