Cancer Medicine (Sep 2024)
Activin levels correlate with lymphocytic infiltration in epithelial ovarian cancer
Abstract
Abstract 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.
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