Diagnostic Utility of RNA-Seq for Evaluation of PD-L1 Expression in Clear Cell Renal Cell Carcinoma.

Although there are immune checkpoint inhibitors (ICIs) available for the treatment of renal cell carcinoma (RCC), the utility of PD-L1 detection by immunohistochemistry (IHC) as a predictive biomarker in clear cell RCC (ccRCC) remains controversial. Nevertheless, alternative methods for PD-L1 detection, such as RNA sequencing (RNA-Seq), may be clinically useful in ccRCC; therefore, we sought to determine the ability of RNA-Seq to accurately and sensitively detect PD-L1 expression across different ccRCC clinical samples in comparison with IHC.

Patients with ccRCC (n=127) who received treatment from Washington University in St. Louis between 2018 and 2020 were identified. Tumors from these patients were analyzed using RNA-Seq and IHC.

PD-L1 detection by RNA-Seq strongly correlated with IHC (P < .001), which was further validated using two independent datasets. Furthermore, RNA-Seq analysis identified an immune-enriched (higher PD-L1 positivity) and an immune-desert (lower PD-L1 positivity) microenvironment of ccRCC, which also correlated with IHC (P < .00001).

The results demonstrate the ability of RNA-Seq to detect PD-L1 in various ccRCC clinical samples compared to IHC. Ultimately, these findings suggest that PD-L1 detection by RNA-Seq can be further developed to determine the clinical utility of this methodology in ccRCC.

Clinical genitourinary cancer. 2021 Jul 10 [Epub ahead of print]

Maria Sorokina, Danil Stupichev, Yang Lyu, Akshaya Ramachandran, Natalia Miheecheva, Jessica H Brown, Krystle Nomie, Ekaterina Postovalova, Alexander Bagaev, Maria Tsiper, James J Hsieh

BostonGene Corporation, Waltham, MA., Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO., Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO. Electronic address: .