Dataset Information

Association of PIK3CA mutation and PTEN loss with expression of CD274 (PD-L1) in colorectal carcinoma.

ABSTRACT: Immunotherapy 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 PIK3CA mutation, 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 PIK3CA mutation 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, KRAS and BRAF mutations. PIK3CA mutation 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]. PIK3CA mutation 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.

SUBMITTER: Ugai T

PROVIDER: S-EPMC8331006 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of <i>PIK3CA</i> mutation and PTEN loss with expression of CD274 (PD-L1) in colorectal carcinoma.

Ugai Tomotaka T Zhao Melissa M Shimizu Takashi T Akimoto Naohiko N Shi Shanshan S Takashima Yasutoshi Y Zhong Rong R Lau Mai Chan MC Haruki Koichiro K Arima Kota K Fujiyoshi Kenji K Langworthy Benjamin B Masugi Yohei Y da Silva Annacarolina A Nosho Katsuhiko K Baba Yoshifumi Y Song Mingyang M Chan Andrew T AT Wang Molin M Meyerhardt Jeffrey A JA Giannakis Marios M Väyrynen Juha P JP Nowak Jonathan A JA Ogino Shuji S

Oncoimmunology 20210802 1

Immunotherapy 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 <i>PIK3CA</i> mutation, PTEN loss, or their combined status might be associated with CD274 overexpression in colorectal carcinoma. We assessed tumor CD274 and PTEN expression by immunohistochem ...[more]

PMID: 34377593

Dataset Information

Association of PIK3CA mutation and PTEN loss with expression of CD274 (PD-L1) in colorectal carcinoma.

Publications

Association of <i>PIK3CA</i> mutation and PTEN loss with expression of CD274 (PD-L1) in colorectal carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Similar Datasets

Tumour CD274 (PD-L1) expression and T cells in colorectal cancer.
| S-EPMC5097696 | biostudies-literature

Histopathological and genotypic characterization of metastatic colorectal carcinoma with PD-L1 (CD274)-expression: Possible roles of tumour micro environmental factors for CD274 expression.
| S-EPMC5653930 | biostudies-literature

Inverse relationship between <i>Fusobacterium nucleatum</i> amount and tumor CD274 (PD-L1) expression in colorectal carcinoma.
| S-EPMC10394676 | biostudies-literature

Clinicopathologic profile, immunophenotype, and genotype of CD274 (PD-L1)-positive colorectal carcinomas.
| S-EPMC7900912 | biostudies-literature

CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity.
| S-EPMC4914266 | biostudies-literature

<i>PD-L1</i> (<i>CD274</i>) promoter methylation predicts survival in colorectal cancer patients.
| S-EPMC5283627 | biostudies-literature

Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression.
| S-EPMC4112370 | biostudies-literature

Characterisation of tumor microenvironment and prevalence of CD274/PD-L1 genetic alterations difference in colorectal Cancer.
| S-EPMC9996909 | biostudies-literature

Spatially resolved multimarker evaluation of CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint expression and macrophage polarisation in colorectal cancer.
| S-EPMC10205752 | biostudies-literature

<i>PD-L1</i> (<i>CD274</i>) promoter hypomethylation predicts immunotherapy response in metastatic urothelial carcinoma.
| S-EPMC10588513 | biostudies-literature