Activin levels correlate with lymphocytic infiltration in epithelial ovarian cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39248018", "kind": "science-record", "revision": 4, "content_hash": "sha256:a5a3e3acb993c517c9b24b1667069fc921b3290b3d70521274e002ede0b19e8f", "created_at": "2026-11-01T20:29:23Z", "updated_at": "2026-11-01T22:55:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Activin levels correlate with lymphocytic infiltration in epithelial ovarian cancer.", "doi": "10.1002/cam4.7368", "pmid": "39248018", "authors": ["Elizabeth T Evans", "Emily F Page", "Alex Seok Choi", "Zainab Shonibare", "Andrea G Kahn", "Rebecca C Arend", "Karthikeyan Mythreye"], "journal": "Cancer medicine", "year": 2024, "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.\nMETHODS: 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.\nRESULTS: 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.\nCONCLUSION: 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.", "claims": [{"id": "claim-method", "statement": "Normalization and downstream analysis for gene quantification was performed with DESeq2 (version 1.38.3). Survival data were generated from the online database KM Plotter, using the Affymetrix Probe ID INHBA (204926_at) and INHBA (2105511_a_atl). Gene expression was split into high and low using the median expression, and log‐rank statistics were utilized to calculate both p‐value and hazard ratio (HR). Multiple comparisons were evaluated using one‐way ANOVA, with Tukey post‐hoc analysis of a significant ANOVA group effect then performed as indicated. We find that when comparing INHBA levels against the 16 immune population signatures, the most significant Pearson's correlation was seen with a Treg signature (Figure 2D). However, using Cox log‐rank hazards regression to analyze the influence of activin‐A levels in ascites on patient OS, we found that activin‐A level in ascites did not correlate strongly with survival outcomes (HR 0.95, 95% confidence interval 0.42–2.16) (Figure 4B,C).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39248018", "locator": "sections[4] \"Bioinformatics\" paragraph 2", "quote": "Normalization and downstream analysis for gene quantification was performed with DESeq2 (version 1.38.3)."}, {"asset": "source:pmid:39248018", "locator": "sections[5] \"Survival analysis\" paragraph 2", "quote": "Survival data were generated from the online database KM Plotter, using the Affymetrix Probe ID INHBA (204926_at) and INHBA (2105511_a_atl)."}, {"asset": "source:pmid:39248018", "locator": "sections[5] \"Survival analysis\" paragraph 2", "quote": "Gene expression was split into high and low using the median expression, and log‐rank statistics were utilized to calculate both p‐value and hazard ratio (HR)."}, {"asset": "source:pmid:39248018", "locator": "sections[8] \"Statistical analysis\" paragraph 2", "quote": "Multiple comparisons were evaluated using one‐way ANOVA, with Tukey post‐hoc analysis of a significant ANOVA group effect then performed as indicated."}, {"asset": "source:pmid:39248018", "locator": "sections[11] \"A lymphocytic gene profile was positively correlated with activin A expression\" paragraph 2", "quote": "We find that when comparing INHBA levels against the 16 immune population signatures, the most significant Pearson's correlation was seen with a Treg signature (Figure 2D)."}, {"asset": "source:pmid:39248018", "locator": "sections[13] \"Activin‐A is elevated in EOC patient ascites\" paragraph 2", "quote": "However, using Cox log‐rank hazards regression to analyze the influence of activin‐A levels in ascites on patient OS, we found that activin‐A level in ascites did not correlate strongly with survival outcomes (HR 0.95, 95% confidence interval 0.42–2.16) (Figure 4B,C)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are all in the manuscript and also available upon request from the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39248018", "locator": "sections[23] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The data that support the findings of this study are all in the manuscript and also available upon request from the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "INHBA expression is elevated within EOC, correlating with worse survival, with activin protein levels correlating with specific immune infiltration.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39248018", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "INHBA expression is elevated within EOC, correlating with worse survival, with activin protein levels correlating with specific immune infiltration."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "INHBA expression is elevated within EOC, correlating with worse survival, with activin protein levels correlating with specific immune infiltration.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39248018"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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However, using Cox log‐rank hazards regression to analyze the influence of activin‐A levels in ascites on patient OS, we found that activin‐A level in ascites did not correlate strongly with survival outcomes (HR 0.95, 95% confidence interval 0.42–2.16) (Figure 4B,C)."}}, {"id": "method-2", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"id": "method-3", "family": "differential_expression", "specific": "deseq2", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.7, "band": "medium", "quote": "DESeq2"}}, {"id": "method-4", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson's correlation"}}, {"id": "method-5", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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Immunohistochemical analysis was performed to evaluate activin A", "o lymphocytic immune markers in EOC samples. Immunohistochemistry analysis revealed a positive correlation of"], "order_basis": "paper_text_order:781", "id": "assay:1"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["markers CD8 and FoxP3 at the protein level. ELISA to activin-A was used to assess levels in th", "for malignancy. 21 , 25 We also performed an ELISA to detect activin‐A within the ascites of 24"], "order_basis": "paper_text_order:902", "id": "assay:2"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Normalization and downstream analysis for gene quantification was performed with DESeq2 (version 1.38.3). Survival data were generated from the online database KM Plotter, using the Affymetrix Probe ID INHBA (204926_at) and INHBA (2105511_a_atl). Gene expression was split into high and low using the median expression, and log‐rank statistics were utilized to calculate both p‐value and hazard ratio (HR). Multiple comparisons were evaluated using one‐way ANOVA, with Tukey post‐hoc analysis of a significant ANOVA group effect then performed as indicated. We find that when comparing INHBA levels against the 16 immune population signatures, the most significant Pearson's correlation was seen with a Treg signature (Figure 2D). However, using Cox log‐rank hazards regression to analyze the influence of activin‐A levels in ascites on patient OS, we found that activin‐A level in ascites did not correlate strongly with survival outcomes (HR 0.95, 95% confidence interval 0.42–2.16) (Figure 4B,C)."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}