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 (US)
Article number1855
JournalCancers
Volume16
Issue number10
DOIs
StatePublished - May 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Keywords

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

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