Characterization of FOLH1 Expression in Renal Cell Carcinoma

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number1855
JournalCancers
Volume16
Issue number10
Early online dateMay 13 2024
DOIs
StatePublished - May 2024

Keywords

  • FOLH1
  • diagnostics
  • molecular profiling
  • renal cell carcinoma
  • therapeutics

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