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

• Published in: Thoracic cancer 2024-10, Vol.15 (29), p.2090-2099
• Main Authors: Koinuma, Yoshika, Mitsuishi, Yoichiro, Winardi, Wira, Hidayat, Moulid, Wirawan, Aditya, Hayakawa, Daisuke, Kanamori, Koichiro, Matsumoto, Naohisa, Hayashi, Takuo, Shimada, Naoko, Tajima, Ken, Takamochi, Kazuya, Takahashi, Fumiyuki, Suzuki, Kenji, Takahashi, Kazuhisa
• Format: Article
• Language: English
• Subjects: AMH‐AMHR2 pathway; Antibodies; cell cycle; Cell growth; cell proliferation; Clinical outcomes; Data analysis; Gene expression; Genomes; Growth factors; Histology; Immunohistochemistry; Kinases; Lung cancer; Medical prognosis; Mutation; non‐small cell lung cancer; Original; Ovarian cancer; Patients; Protein expression; Proteins
• ISSN: 1759-7706; 1759-7714; 1759-7714
• DOI: 10.1111/1759-7714.15309

Background Non‐small cell lung cancer (NSCLC) is the leading cause of cancer‐related deaths worldwide despite advances in cancer therapeutics. In several gynecological cancers, anti‐Müllerian hormone receptor type 2 (AMHR2) mediates AMH‐induced 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 AMH‐AMHR2 pathway suppressed cell proliferation. Conclusion In lung adenocarcinoma tissues with high expression of AMHR2, activation of the AMH‐AMHR2 pathway may suppress cell proliferation. ·Some lung adenocarcinoma clinical specimens express the AMHR2 protein. In lung adenocarcinoma tissues with high AMHR2 expression, activation of the AMH–AMHR2 pathway may suppress cell proliferation. ·This study unveils potential therapeutic targets for future research by suggesting that the AMH–AMHR2 pathway plays a role in suppressing cancer progression in cases of lung adenocarcinoma with high AMHR2 expression.