Given the emergence of PSMA-targeted diagnostic agents and therapeutics, we sought to investigate patterns of FOLH1 expression in RCC and their impacts on RCC outcomes.
We conducted a pooled multi-institutional analysis of patients with RCC having undergone DNA and RNA next-generation sequencing. FOLH1-high/low expression was defined as the ≥75th/<25th percentile of RNA transcripts per million (TPM). Angiogenic, T-effector, and myeloid expression signatures were calculated using previously defined gene sets. Kaplan-Meier estimates were calculated from the time of tissue collection or therapy start.
We included 1,724 patients in the analysis. FOLH1 expression was significantly higher in clear cell (71%) compared to non-clear cell RCC tumors (19.0 versus 3.3 TPM, p < 0.001) and varied by specimen site (45% primary kidney/55% metastasis, 13.6 versus 9.9 TPM, p < 0.001). FOLH1 expression was correlated with angiogenic gene expression (Spearman = 0.76, p < 0.001) and endothelial cell abundance (Spearman = 0.76, p < 0.001). While OS was similar in patients with FOLH1-high versus -low ccRCC, patients with FOLH1-high clear cell tumors experienced a longer time on cabozantinib treatment (9.7 versus 4.6 months, respectively, HR 0.57, 95% CI 0.35-0.93, p < 0.05).
We observed differential patterns of FOLH1 expression based on histology and tumor site in RCC. FOLH1 was correlated with angiogenic gene expression, increased OS, and a longer duration of cabozantinib treatment.
Cancers. 2024 May 13*** epublish ***
Eric Ovruchesky, Elizabeth Pan, Melis Guer, Andrew Elliott, Shankar Siva, Praful Ravi, Bradley McGregor, Aditya Bagrodia, Ithaar Derweesh, Pedro Barata, Elisabeth I Heath, Emmanuel S Antonarakis, Sourat Darabi, Dave S B Hoon, Amir Mortazavi, Toni K Choueiri, Chadi Nabhan, Shuanzeng Wei, Rana R McKay
Division of Urologic Oncology, Department of Oncology, Moores Cancer Center, University of California San Diego, San Diego, CA 92037, USA., Department of Clinical and Translational Research, Caris Life Sciences, Inc., Phoenix, AZ 85040, USA., Division of Radiation Oncology and Cancer Imaging, Department of Oncology, Peter MacCallum Cancer Centre, the University of Melbourne, Melbourne, VIC 3052, Australia., The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Hematology and Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH 44106, USA., Department of Oncology, Wayne State University, Karmanos Cancer Institute, Detroit, MI 48201, USA., Department of Hematology and Oncology, University of Minnesota, Masonic Cancer Center, Minneapolis, MN 55455, USA., Clinical Genomics, Hoag Family Cancer Institute, Newport Beach, CA 92663, USA., Department of Translational Molecular Medicine, Saint John's Cancer Institute, Providence Health Systems, Santa Monica, CA 90404, USA., Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University, The Comprehensive Cancer Center, Columbus, OH 43210, USA., Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.