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Association of PIK3CAmutation and PTEN loss with expression of CD274 (PD-L1) in colorectal carcinoma

Authors :
Ugai, Tomotaka
Zhao, Melissa
Shimizu, Takashi
Akimoto, Naohiko
Shi, Shanshan
Takashima, Yasutoshi
Zhong, Rong
Lau, Mai Chan
Haruki, Koichiro
Arima, Kota
Fujiyoshi, Kenji
Langworthy, Benjamin
Masugi, Yohei
da Silva, Annacarolina
Nosho, Katsuhiko
Baba, Yoshifumi
Song, Mingyang
Chan, Andrew T.
Wang, Molin
Meyerhardt, Jeffrey A.
Giannakis, Marios
Väyrynen, Juha P.
Nowak, Jonathan A.
Ogino, Shuji
Source :
OncoImmunology; January 2021, Vol. 10 Issue: 1
Publication Year :
2021

Abstract

ABSTRACTImmunotherapy targeting the CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint axis has emerged as a promising treatment strategy for various cancers. Experimental evidence suggests that phosphatidylinositol-4,5-bisphosphonate 3-kinase (PI3K) signaling may upregulate CD274 expression. Thus, we hypothesized that PIK3CAmutation, PTEN loss, or their combined status might be associated with CD274 overexpression in colorectal carcinoma. We assessed tumor CD274 and PTEN expression by immunohistochemistry and assessed PIK3CAmutation by pyrosequencing in 753 patients among 4,465 incident rectal and colon cancer cases that had occurred in two U.S.-wide prospective cohort studies. To adjust for potential confounders and selection bias due to tissue availability, inverse probability weighted multivariable ordinal logistic regression analyses used the 4,465 cases and tumoral data including microsatellite instability, CpG island methylator phenotype, KRASand BRAFmutations. PIK3CAmutation and loss of PTEN expression were detected in 111 of 753 cases (15%) and 342 of 585 cases (58%), respectively. Tumor CD274 expression was negative in 306 (41%), low in 195 (26%), and high in 252 (33%) of 753 cases. PTEN loss was associated with CD274 overexpression [multivariable odds ratio (OR) 1.83; 95% confidence interval (CI), 1.22–2.75; P= .004]. PIK3CAmutation was statistically-insignificantly (P= .036 with the stringent alpha level of 0.005) associated with CD274 overexpression (multivariable OR, 1.54; 95% CI, 1.03–2.31). PIK3CA-mutated PTEN-lost tumors (n = 33) showed higher prevalence of CD274-positivity (82%) than PIK3CA-wild-type PTEN-lost tumors (n = 204; 70% CD274-positivity) and PTEN-expressed tumors (n = 147; 50% CD274-positivity) (P= .003). Our findings support the role of PI3K signaling in the CD274/PDCD1 pathway.

Details

Language :
English
ISSN :
21624011 and 2162402X
Volume :
10
Issue :
1
Database :
Supplemental Index
Journal :
OncoImmunology
Publication Type :
Periodical
Accession number :
ejs58595671
Full Text :
https://doi.org/10.1080/2162402X.2021.1956173