Activin levels correlate with lymphocytic infiltration in epithelial ovarian cancer.

Publisher: John Wiley & Sons Ltd Country of Publication: United States NLM ID: 101595310 Publication Model: Print Cited Medium: Internet ISSN: 2045-7634 (Electronic) Linking ISSN: 20457634 NLM ISO Abbreviation: Cancer Med Subsets: MEDLINE

Original Publication: [Malden, MA] : John Wiley & Sons Ltd., c2012-

Carcinoma, Ovarian Epithelial*/pathology ; Carcinoma, Ovarian Epithelial*/immunology ; Carcinoma, Ovarian Epithelial*/metabolism ; Carcinoma, Ovarian Epithelial*/genetics ; Carcinoma, Ovarian Epithelial*/mortality ; Ovarian Neoplasms*/pathology ; Ovarian Neoplasms*/immunology ; Ovarian Neoplasms*/metabolism ; Ovarian Neoplasms*/mortality ; Ovarian Neoplasms*/genetics ; Inhibin-beta Subunits*/genetics ; Inhibin-beta Subunits*/metabolism ; Activins*/metabolism ; Activins*/genetics; Humans ; Female ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/metabolism ; Middle Aged ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/metabolism ; Biomarkers, Tumor/genetics ; Forkhead Transcription Factors/metabolism ; Forkhead Transcription Factors/genetics

Objective: The TGF-β superfamily member activin, a dimer of the gene products of INHBA and/or INHBB, has been implicated in immune cell maturation and recruitment, but its immune impact within epithelial ovarian cancer (EOC) is not well characterized. We sought to explore differences in activin (INHBA/ Inhibin-βA and INHBB/ Inhibin-βB) between malignant and ovarian tissues at the RNA and protein level and assess the relationship between activin and immune cells in EOC.
Methods: Publicly available RNA sequencing data were accessed from GEO (#GSE143897) with normalization and quantification performed via DESeq2. Immune gene expression profile was further explored within the TCGA-OV cohort derived from The Cancer Genome Atlas (TCGA). Immunohistochemical analysis was performed to evaluate activin A and T-cell markers CD8 and FoxP3 at the protein level. ELISA to activin-A was used to assess levels in the ascites of advanced EOC patients. Kaplan-Meier curves were generated to visualize survival outcomes.
Results: Gene expression levels of components of the activin signaling pathway were elevated within EOC when compared to a benign cohort, with differences in activin type I/II receptor gene profiles identified. Additionally, INHBA gene expression was linked to lymphocytic immune markers in EOC samples. Immunohistochemistry analysis revealed a positive correlation of CD8 and FOXP3 staining with activin A at the protein level in both primary and metastatic epithelial ovarian cancer samples. Furthermore, Activin-A (inhibin-βA) is significantly elevated in EOC patient ascites.
Conclusion: INHBA expression is elevated within EOC, correlating with worse survival, with activin protein levels correlating with specific immune infiltration. Our findings suggest that activin-A may play a role in suppressing anti-tumor immunity in EOC, highlighting its potential as a therapeutic target.
(© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

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T32 CA229102 United States CA NCI NIH HHS; NCI T32CA229102 Division of Cancer Prevention, National Cancer Institute; NCI R01CA219495 Division of Cancer Prevention, National Cancer Institute

Keywords: activin; metastasis; ovarian cancer; tumor immune infiltration

93443-12-0 (Inhibin-beta Subunits)
0 (inhibin beta A subunit)
104625-48-1 (Activins)
0 (INHBB protein, human)
0 (activin A)
0 (Biomarkers, Tumor)
0 (Forkhead Transcription Factors)

Date Created: 20240909 Date Completed: 20240909 Latest Revision: 20240911

20240911

PMC11381957

10.1002/cam4.7368

39248018