Folate receptor alpha in ovarian cancer tissue and patient serum is associated with disease burden and treatment outcomes.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
20
07
2021
accepted:
14
10
2022
revised:
30
09
2022
pubmed:
20
11
2022
medline:
9
2
2023
entrez:
19
11
2022
Statut:
ppublish
Résumé
Survival rates for ovarian cancer remain poor, and monitoring and prediction of therapeutic response may benefit from additional markers. Ovarian cancers frequently overexpress Folate Receptor alpha (FRα) and the soluble receptor (sFRα) is measurable in blood. Here we investigated sFRα as a potential biomarker. We evaluated sFRα longitudinally, before and during neo-adjuvant, adjuvant and palliative therapies, and tumour FRα expression status by immunohistrochemistry. The impact of free FRα on the efficacy of anti-FRα treatments was evaluated by an antibody-dependent cellular cytotoxicity assay. Membrane and/or cytoplasmic FRα staining were observed in 52.7% tumours from 316 ovarian cancer patients with diverse histotypes. Circulating sFRα levels were significantly higher in patients, compared to healthy volunteers, specifically in patients sampled prior to neoadjuvant and palliative treatments. sFRα was associated with FRα cell membrane expression in the tumour. sFRα levels decreased alongside concurrent tumour burden in patients receiving standard therapies. High concentrations of sFRα partly reduced anti-FRα antibody tumour cell killing, an effect overcome by increased antibody doses. sFRα may present a non-invasive marker for tumour FRα expression, with the potential for monitoring patient response to treatment. Larger, prospective studies should evaluate FRα for assessing disease burden and response to systemic treatments.
Sections du résumé
BACKGROUND
Survival rates for ovarian cancer remain poor, and monitoring and prediction of therapeutic response may benefit from additional markers. Ovarian cancers frequently overexpress Folate Receptor alpha (FRα) and the soluble receptor (sFRα) is measurable in blood. Here we investigated sFRα as a potential biomarker.
METHODS
We evaluated sFRα longitudinally, before and during neo-adjuvant, adjuvant and palliative therapies, and tumour FRα expression status by immunohistrochemistry. The impact of free FRα on the efficacy of anti-FRα treatments was evaluated by an antibody-dependent cellular cytotoxicity assay.
RESULTS
Membrane and/or cytoplasmic FRα staining were observed in 52.7% tumours from 316 ovarian cancer patients with diverse histotypes. Circulating sFRα levels were significantly higher in patients, compared to healthy volunteers, specifically in patients sampled prior to neoadjuvant and palliative treatments. sFRα was associated with FRα cell membrane expression in the tumour. sFRα levels decreased alongside concurrent tumour burden in patients receiving standard therapies. High concentrations of sFRα partly reduced anti-FRα antibody tumour cell killing, an effect overcome by increased antibody doses.
CONCLUSIONS
sFRα may present a non-invasive marker for tumour FRα expression, with the potential for monitoring patient response to treatment. Larger, prospective studies should evaluate FRα for assessing disease burden and response to systemic treatments.
Identifiants
pubmed: 36402875
doi: 10.1038/s41416-022-02031-x
pii: 10.1038/s41416-022-02031-x
pmc: PMC9902484
doi:
Substances chimiques
Folate Receptor 1
0
FOLR1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
342-353Subventions
Organisme : Cancer Research UK (CRUK)
ID : C30122/A11527
Organisme : DH | National Institute for Health Research (NIHR)
ID : CL-2020-17-002
Organisme : Cancer Research UK (CRUK)
ID : C30122/A15774
Organisme : Medical Research Council
ID : MR/L023091/1
Pays : United Kingdom
Organisme : Cancer Research UK (CRUK)
ID : C604/A25135
Organisme : CSP VA
ID : 573
Pays : United States
Organisme : Breast Cancer Now (BCN)
ID : 147; KCL-BCN-Q3
Informations de copyright
© 2022. The Author(s).
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