title: Folate receptor-α (FOLR1) expression and function in triple negative tumors.
abstract: Folate receptor alpha (FOLR1) has been identified as a potential prognostic and therapeutic target in a number of cancers. A correlation has been shown between intense overexpression of FOLR1 in breast tumors and poor prognosis, yet there is limited examination of the distribution of FOLR1 across clinically relevant breast cancer subtypes. To explore this further, we used RNA-seq data from multiple patient cohorts to analyze the distribution of FOLR1 mRNA across breast cancer subtypes comprised of estrogen receptor positive (ER+), human epidermal growth factor receptor positive (HER2+), and triple negative (TNBC) tumors. FOLR1 expression varied within breast tumor subtypes; triple negative/basal tumors were significantly associated with increased expression of FOLR1 mRNA, compared to ER+ and HER2+ tumors. However, subsets of high level FOLR1 expressing tumors were observed in all clinical subtypes. These observations were supported by immunohistochemical analysis of tissue microarrays, with the largest number of 3+ positive tumors and highest H-scores of any subtype represented by triple negatives, and lowest by ER+ tumors. FOLR1 expression did not correlate to common clinicopathological parameters such as tumor stage and nodal status. To delineate the importance of FOLR1 overexpression in triple negative cancers, RNA-interference was used to deplete FOLR1 in overexpressing triple negative cell breast lines. Loss of FOLR1 resulted in growth inhibition, whereas FOLR1 overexpression promoted folate uptake and growth advantage in low folate conditions. Taken together, our data suggests patients with triple negative cancers expressing high FOLR1 expression represent an important population of patients that may benefit from targeted anti-FOLR1 therapy. This may prove particularly helpful for a large number of patients who would typically be classified as triple negative and who to this point have been left without any targeted treatment options.
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United Sates of America.
authors: Brian M
authors: BM
authors: Necela
authors: Department of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida, United States of America.
authors: Jennifer A
authors: JA
authors: Crozier
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United Sates of America.
authors: Cathy A
authors: CA
authors: Andorfer
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United Sates of America.
authors: Laura
authors: L
authors: Lewis-Tuffin
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United Sates of America.
authors: Jennifer M
authors: JM
authors: Kachergus
authors: Department of Pathology and Laboratory Medicine, Mayo Clinic, Jacksonville, Florida, United States of America.
authors: Xochiquetzal J
authors: XJ
authors: Geiger
authors: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Krishna R
authors: KR
authors: Kalari
authors: Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida United States of America.
authors: Daniel J
authors: DJ
authors: Serie
authors: Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Zhifu
authors: Z
authors: Sun
authors: Department of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida, United States of America.
authors: Alvaro
authors: A
authors: Moreno-Aspitia
authors: Alvaro Moreno
authors: AM
authors: Aspita
authors: Department of Translational Medicine and Diagnostics, Morphotek, Exton, Pennsylvania, United States of America.
authors: Daniel J
authors: DJ
authors: O'Shannessy
authors: Department of Clinical Development, Morphotek, Exton, Pennsylvania, United States of America.
authors: Julia D
authors: JD
authors: Maltzman
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona, United States of America.
authors: Ann E
authors: AE
authors: McCullough
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona, United States of America.
authors: Barbara A
authors: BA
authors: Pockaj
authors: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors: Heather E
authors: HE
authors: Cunliffe
authors: Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: Karla V
authors: KV
authors: Ballman
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United Sates of America.
authors: E Aubrey
authors: EA
authors: Thompson
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United Sates of America.
authors: Edith A
authors: EA
authors: Perez
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D058975:Folate Receptor 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D012333:RNA, Messenger