Anti-Müllerian hormone type II receptor protein expression in non-small cell lung cancer and the effect of AMH/AMHR2 signaling on cancer cell proliferation

Sep 21, 2026

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Background: Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related death despite therapeutic advances. Anti-Müllerian hormone receptor type 2 (AMHR2) mediates AMH-induced growth inhibition in several gynecological cancers, and a subset of NSCLCs shows high AMHR2 expression, yet the clinical relevance and functional role are not fully defined. Methods: Immunostaining of 79 NSCLC surgical specimens, TCGA RNA-seq analysis, and gene ontology/gene set enrichment were combined with in vitro AMHR2 overexpression and recombinant AMH stimulation to test AMH-AMHR2 effects on proliferation. Results: AMHR2 positivity occurred in 16.5% of lung adenocarcinoma cases and not in squamous carcinomas; AMHR2-high tumors showed downregulation of cell-cycle related genes and AMH-AMHR2 pathway activation suppressed proliferation. Conclusion: In lung adenocarcinoma with high AMHR2, AMH-AMHR2 signaling may inhibit cancer cell proliferation.

LanguageEnglish

CategoryResearch & Report

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Pages10

Reading Time25 min

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Abstract

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Methods

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DOI: 10.1111/1759-7714.15309 ORIGINA L ARTICLE Anti-Müllerian hormone type II receptor protein expression in non-small cell lung cancer and the effect of AMH/AMHR2 signaling on cancer cell proliferation Yoshika Koinuma 1,2 | Yoichiro Mitsuishi 1,2 | Wira Winardi 1,2 | Moulid Hidayat 1,2 | Aditya Wirawan 1,2 | Daisuke Hayakawa 1,2 | Koichiro Kanamori 1,2 | Naohisa Matsumoto 1,2 | Takuo Hayashi 3 | Naoko Shimada 1,2 | Ken Tajima 1,2 | Kazuya Takamochi 4 | Fumiyuki Takahashi 1,2 | Kenji Suzuki 4 | Kazuhisa Takahashi 1,2 1Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, Tokyo, Japan 2Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, Tokyo, Japan 3Department of Human Pathology, Juntendo University, Graduate School of Medicine, Tokyo, Japan 4Department of General Thoracic Surgery, Juntendo University, Graduate School of Medicine, Tokyo, Japan Correspondence Yoichiro Mitsuishi, Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan. [Email:](Email: y-mitsuishi@juntendo.ac.jp)[ y-mitsuishi@juntendo.ac.jp](Email: y-mitsuishi@juntendo.ac.jp) Funding information Japan Society for the Promotion of Science, Grant/Award Numbers: 15K09230, 23K07636; Institute for Environmental and Gender-specific Medicine Abstract Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancerrelated deaths worldwide despite advances in cancer therapeutics. In several gynecological cancers, anti-Müllerian hormone receptor type 2 (AMHR2) mediates AMHinduced growth inhibition and is expressed at high levels. Furthermore, 5%–8% of NSCLCs exhibit high AMHR2 expression, suggesting that AMH may inhibit the progression of some lung cancers. However, the clinical relevance of AMHR2 expression and its role in lung cancer is not fully clarified. Methods: Immunostaining was performed on 79 surgical specimens of NSCLC. The Cancer Genome Atlas RNA-seq data for lung adenocarcinoma were analyzed, and gene ontology and gene set enrichment analyses were performed. In cellular experiments, AMHR2-overexpressing NSCLC cell lines were established, and the role of the AMH-AMHR2 pathway in cell proliferation with recombinant human AMH protein treatment was examined. Results: A total of 13 cases (16.5%) were positive for immunostaining in lung adenocarcinoma tissues; no positive signals were detected in lung squamous carcinoma tissues. Gene expression variation analysis using The Cancer Genome Atlas data showed that the expression of genes related to the cell cycle was downregulated in the AMHR2-high group. Cellular experiments showed that activation of the AMHAMHR2 pathway suppressed cell proliferation. Conclusion: In lung adenocarcinoma tissues with high expression of AMHR2, activation of the AMH-AMHR2 pathway may suppress cell proliferation. KEYW ORD S AMH-AMHR2 pathway, cell cycle, cell proliferation, non-small cell lung cancer INTRODUCTION Lung cancer is one of the most common cancers worldwide, leading to both high incidence and mortality.1 Recent research has shown that subsets of non-small cell lung cancer (NSCLC) can be distinguished based on recurrent driver mutations in different oncogenes.2 The advent of molecular targeted therapies, particularly those targeting receptor tyrosine kinases in advanced NSCLC (e.g., mutations in the epidermal growth factor receptor [EGFR] or anaplastic lymphoma kinase [ALK] genes), has revolutionized lung cancer treatment. Although the introduction of these targeted drugs along with recent developments in immune checkpoint inhibitors has significantly improved the This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Thoracic Cancer published by John Wiley &

FAQs

What study question addresses AMHR2 in NSCLC?

The study examines whether AMHR2 expression and AMH/AMHR2 signaling have clinical relevance and functional impact on NSCLC, particularly cancer cell proliferation.

How was AMHR2 expression evaluated in the research?

AMHR2 protein expression was assessed by immunostaining in 79 NSCLC surgical specimens, and TCGA RNA-seq data were analyzed for expression patterns and pathway-related changes.

What were the key findings about AMHR2-high adenocarcinoma and proliferation?

AMHR2 immunostaining was positive in 16.5% of lung adenocarcinoma cases, not in squamous carcinoma, and AMHR2-high groups showed downregulation of cell-cycle genes; in cell experiments, AMH-AMHR2 activation suppressed proliferation.

Sep 21, 2026

Uploaded by Riley