Characterization of FOLH1 Expression in Renal Cell Carcinoma

• Published in: Cancers Vol. 16; no. 10; p. 1855
• Main Authors: Ovruchesky, Eric, Pan, Elizabeth, Guer, Melis, Elliott, Andrew, Siva, Shankar, Ravi, Praful, McGregor, Bradley, Bagrodia, Aditya, Derweesh, Ithaar, Barata, Pedro, Heath, Elisabeth I, Antonarakis, Emmanuel S, Darabi, Sourat, Hoon, Dave S B, Mortazavi, Amir, Choueiri, Toni K, Nabhan, Chadi, Wei, Shuanzeng, McKay, Rana R
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13-05-2024
• Subjects: Angiogenesis; Antigens; Clinical outcomes; Diagnostic agents; DNA sequencing; Endothelial cells; FOLH1 gene; Gene expression; Genes; Histology; Kidney cancer; Lymphatic system; Medical diagnosis; Metastases; Metastasis; Mutation; Next-generation sequencing; Patients; Prostate cancer; Renal cell carcinoma; Survival analysis; Tomography; Tumors; United States > US; diagnostics; renal cell carcinoma; therapeutics; FOLH1; molecular profiling
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16101855

Given the emergence of PSMA-targeted diagnostic agents and therapeutics, we sought to investigate patterns of
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.
-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,
< 0.001) and varied by specimen site (45% primary kidney/55% metastasis, 13.6 versus 9.9 TPM,
< 0.001).
expression was correlated with angiogenic gene expression (Spearman = 0.76,
< 0.001) and endothelial cell abundance (Spearman = 0.76,
< 0.001). While OS was similar in patients with
-high versus -low ccRCC, patients with
-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,
< 0.05).
We observed differential patterns of
expression based on histology and tumor site in RCC.
was correlated with angiogenic gene expression, increased OS, and a longer duration of cabozantinib treatment.