{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:06:41Z","timestamp":1787580401118,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NCI Cancer Center Support Grant","award":["P30 CA077598"],"award-info":[{"award-number":["P30 CA077598"]}]},{"name":"NCI Cancer Center Support Grant","award":["W81XWH-22-2-0025"],"award-info":[{"award-number":["W81XWH-22-2-0025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 \u226575th\/&lt;25th percentile of RNA transcripts per million (TPM). Angiogenic, T-effector, and myeloid expression signatures were calculated using previously defined gene sets. Kaplan\u2013Meier 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 &lt; 0.001) and varied by specimen site (45% primary kidney\/55% metastasis, 13.6 versus 9.9 TPM, p &lt; 0.001). FOLH1 expression was correlated with angiogenic gene expression (Spearman = 0.76, p &lt; 0.001) and endothelial cell abundance (Spearman = 0.76, p &lt; 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\u20130.93, p &lt; 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.<\/jats:p>","DOI":"10.3390\/cancers16101855","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T08:33:03Z","timestamp":1715589183000},"page":"1855","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Characterization of FOLH1 Expression in Renal Cell Carcinoma"],"prefix":"10.3390","volume":"16","author":[{"given":"Eric","family":"Royz","sequence":"first","affiliation":[{"name":"Division of Urologic Oncology, Department of Oncology, Moores Cancer Center, University of California San Diego, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Pan","sequence":"additional","affiliation":[{"name":"Division of Urologic Oncology, Department of Oncology, Moores Cancer Center, University of California San Diego, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melis","family":"Guer","sequence":"additional","affiliation":[{"name":"Division of Urologic Oncology, Department of Oncology, Moores Cancer Center, University of California San Diego, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-8031","authenticated-orcid":false,"given":"Andrew","family":"Elliott","sequence":"additional","affiliation":[{"name":"Department of Clinical and Translational Research, Caris Life Sciences, Inc., Phoenix, AZ 85040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2840-0658","authenticated-orcid":false,"given":"Shankar","family":"Siva","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology and Cancer Imaging, Department of Oncology, Peter MacCallum Cancer Centre, the University of Melbourne, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praful","family":"Ravi","sequence":"additional","affiliation":[{"name":"The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8298-0289","authenticated-orcid":false,"given":"Bradley","family":"McGregor","sequence":"additional","affiliation":[{"name":"The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Bagrodia","sequence":"additional","affiliation":[{"name":"Division of Urologic Oncology, Department of Oncology, Moores Cancer Center, University of California San Diego, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ithaar","family":"Derweesh","sequence":"additional","affiliation":[{"name":"Division of Urologic Oncology, Department of Oncology, Moores Cancer Center, University of California San Diego, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8890-2951","authenticated-orcid":false,"given":"Pedro","family":"Barata","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1381-2713","authenticated-orcid":false,"given":"Elisabeth","family":"Heath","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University, Karmanos Cancer Institute, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3531-3851","authenticated-orcid":false,"given":"Emmanuel","family":"Antonarakis","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University of Minnesota, Masonic Cancer Center, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3395-894X","authenticated-orcid":false,"given":"Sourat","family":"Darabi","sequence":"additional","affiliation":[{"name":"Clinical Genomics, Hoag Family Cancer Institute, Newport Beach, CA 92663, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Hoon","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Medicine, Saint John\u2019s Cancer Institute, Providence Health Systems, Santa Monica, CA 90404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Mortazavi","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University, The Comprehensive Cancer Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Choueiri","sequence":"additional","affiliation":[{"name":"The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chadi","family":"Nabhan","sequence":"additional","affiliation":[{"name":"Department of Clinical and Translational Research, Caris Life Sciences, Inc., Phoenix, AZ 85040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuanzeng","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"McKay","sequence":"additional","affiliation":[{"name":"Division of Urologic Oncology, Department of Oncology, Moores Cancer Center, University of California San Diego, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"ref_1","first-page":"2022","article-title":"Renal cell carcinoma: An overview of the epidemiology, diagnosis, and treatment","volume":"39","author":"Bahadoram","year":"2022","journal-title":"G. 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