TY - JOUR
T1 - Chromosomal instability may not be a predictor for immune checkpoint inhibitors from a comprehensive bioinformatics analysis
AU - Wu, Chiao En
AU - Yeh, Da Wei
AU - Pan, Yi Ru
AU - Huang, Wen Kuan
AU - Chen, Ming Huang
AU - Chang, John Wen Cheng
AU - Chen, Jen Shi
AU - Wang, Yu Chao
AU - Yeh, Chun Nan
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - CIN70
KW - Chromosomal instability
KW - Immune checkpoint inhibitors
KW - Immunotherapy
KW - Microsatellite instability
KW - Tumor mutation burden
UR - http://www.scopus.com/inward/record.url?scp=85096016595&partnerID=8YFLogxK
U2 - 10.3390/life10110276
DO - 10.3390/life10110276
M3 - Article
AN - SCOPUS:85096016595
SN - 2075-1729
VL - 10
SP - 1
EP - 10
JO - Life
JF - Life
IS - 11
M1 - 276
ER -