Activin levels correlate with lymphocytic infiltration in epithelial ovarian cancer

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2024-09-09 DOI:10.1002/cam4.7368

Elizabeth T. Evans, Emily F. Page, Alex Seok Choi, Zainab Shonibare, Andrea G. Kahn, Rebecca C. Arend, Karthikeyan Mythreye

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引用次数: 0

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.

Abstract Image

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激活素水平与上皮性卵巢癌的淋巴细胞浸润有关。

目的：TGF-β超家族成员活化素是INHBA和/或INHBB基因产物的二聚体，被认为与免疫细胞的成熟和招募有关，但其在上皮性卵巢癌（EOC）中的免疫影响尚未得到很好的描述。我们试图从RNA和蛋白质水平探讨恶性肿瘤组织和卵巢组织中活化素（INHBA/抑制素-βA和INHBB/抑制素-βB）的差异，并评估活化素与EOC中免疫细胞之间的关系：方法：从GEO（#GSE143897）获取公开的RNA测序数据，并通过DESeq2进行归一化和量化。在癌症基因组图谱（The Cancer Genome Atlas，TCGA）的TCGA-OV队列中进一步探讨了免疫基因表达谱。免疫组化分析在蛋白质水平上评估了活化素A和T细胞标记物CD8及FoxP3。用酶联免疫吸附法评估晚期EOC患者腹水中的活化素A水平。生成的 Kaplan-Meier 曲线显示了生存结果：结果：与良性病例相比，EOC中活化素信号通路成分的基因表达水平升高，活化素I型/II型受体基因谱存在差异。此外，INHBA基因表达与EOC样本中的淋巴细胞免疫标记物有关。免疫组化分析表明，在原发性和转移性上皮性卵巢癌样本中，CD8和FOXP3染色与蛋白水平的激活素A呈正相关。此外，EOC患者腹水中的活化素A（抑制素-βA）明显升高：结论：INHBA 在 EOC 中的表达升高，与生存恶化相关，而激活素蛋白水平与特异性免疫浸润相关。我们的研究结果表明，活化素-A可能在EOC中起到抑制抗肿瘤免疫的作用，这凸显了其作为治疗靶点的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.

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