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Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas. | LitMetric

Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas.

Pathol Res Pract

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Center of Companion Diagnostics, Samsung Medical Center, Seoul, Republic of Korea. Electronic address:

Published: January 2023

AI Article Synopsis

Article Abstract

Background: Ample evidence supports the potential of programmed death-ligand 1 (PD-L1) expression, detected by immunohistochemistry, as a predictive biomarker for immunotherapy in patients with advanced cancers. To predict the response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas, we aimed to replace PD-L1 combined positive score (CPS) with CD274 mRNA in the original four-gene signature and PD-L1 CPS model developed by us.

Method: We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression levels of five target genes in a cohort of 49 patients (33 with gastric cancer and 16 with urothelial carcinoma) who had received immunotherapy and whose therapeutic responses were available. The predictive performance was evaluated using R package maxstat.

Results: Cutoff values of mRNA expression level were measured using the log-rank statistics for progression-free survival (PFS). Based on these cutoffs, immunotherapy responses were predicted and sorted into responder (n = 12, 24.5%) and non-responder (n = 37, 75.5%) groups. The median PFS values of predicted responders and non-responders were 14.8 months (95% confidence interval [CI]: 0-34.7) and 4.7 months (95% CI: 1.0-8.4, p = 0.02), respectively. Among the 12 predicted responders, 10 had microsatellite-stable tumors with a low tumor mutational burden. The actual clinical responses (complete and partial) were higher in the responder group than those in the non-responder group: 83.3% and 16.2%, respectively.

Conclusion: We modified a predictive biomarker for CD274 mRNA expression to predict the response to immunotherapy in patients with gastric or urothelial carcinomas.

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Source
http://dx.doi.org/10.1016/j.prp.2022.154233DOI Listing

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