Characterization of FOLH1 Expression in Renal Cell Carcinoma

Ovruchesky, E; Pan, E; Guer, M; Elliott, A; Siva, S; Ravi, P; McGregor, B; Bagrodia, A; Derweesh, I; Barata, P; Heath, EI; Antonarakis, ES; Darabi, S; Hoon, DSB; Mortazavi, A; Choueiri, TK; Nabhan, C; Wei, S; McKay, RR

Author(s): Ovruchesky, E; Pan, E; Guer, M; Elliott, A; Siva, S; Ravi, P; McGregor, B; Bagrodia, A; Derweesh, I; Barata, P; Heath, EI; Antonarakis, ES; Darabi, S; Hoon, DSB; Mortazavi, A; Choueiri, TK; Nabhan, C; Wei, S; McKay, RR;
Details: Publication Year 2024-05-13,Volume 16,Issue #10,Page 1855
Journal Title: Cancers
Publication Type: Research article
Abstract: PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Publisher: MDPI
Keywords: Folh1; diagnostics; molecular profiling; renal cell carcinoma; therapeutics
Department(s): Radiation Oncology
Publisher's Version: https://doi.org/10.3390/cancers16101855
Open Access at Publisher's Site: https://doi.org/10.3390/cancers16101855
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-07-17 04:32:33

Last Modified: 2024-07-17 04:35:46