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已发表论文
异常激活的 MNX1 促进表皮生长因子受体突变型肺腺癌的肿瘤生长和奥希替尼耐药性，并可预测生存期
Authors Gu W, Gan J, Liu P, Lai J, Liu C , Zhang G, Shi C, Jiang Q, Qiu F
Received 14 May 2025
Accepted for publication 6 November 2025
Published 20 December 2025 Volume 2025:19 Pages 11411—11431
DOI https://doi.org/10.2147/DDDT.S535214
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 5
Editor who approved publication: Professor Anastasios Lymperopoulos
Weiguo Gu,1,* Jinyu Gan,1,* Penghui Liu,1 Jianfei Lai,1 Chaoxing Liu,1 Guohua Zhang,2,3 Chao Shi,1 Qingkun Jiang,4 Feng Qiu1
1Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Oncology, Gaoxin Branch of the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Nanchang Key Laboratory of Tumor Gene Diagnosis and Innovative Treatment Research, Nanchang, Jiangxi, People’s Republic of China; 4Jiangxi Provincial Key Laboratory of Oral Diseases, Department of Stomatology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Feng Qiu, Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yong Wai Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Email ndyfy01149@ncu.edu.cn Qingkun Jiang, Jiangxi Provincial Key Laboratory of Oral Diseases, Department of Stomatology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yong Wai Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Email ndyfy10001@ncu.edu.cn
Background: Bypass signaling plays an important role in mediating osimertinib resistance in lung adenocarcinoma (LUAD) with epidermal growth factor receptor (EGFR) mutations; however, the role of abnormally activated motor neuron and pancreas homeobox 1 (MNX1) in mediating osimertinib resistance in EGFR-mutant LUAD is unknown.
Methods: Bioinformatics and immunohistochemistry(IHC) analysis identified the MNX1 expression levels in LUAD. The effects of MNX1 and osimertinib on LUAD cell proliferation, invasion, migration, and apoptosis were evaluated using the cell counting kit-8, scratch, EdU, chamber transwell, and flow cytometry assays in vitro. In vivo, the effect of MNX1 expression on tumorigenicity was evaluated using subcutaneous transplanted tumors in nude mice.
Results: Bioinformatics databases and tumor tissue analysis revealed elevated MNX1 expression in LUAD tumor tissues, with high MNX1 expression correlating with poor prognosis. The receiver-operating characteristic(ROC) curve demonstrated that MNX1 has high specificity and sensitivity in diagnosing LUAD from the TCGA dataset. Multivariable COX analysis identified MNX1 as independent prognostic factors for overall survival (OS) in LUAD. Nomogram and calibration plots indicated that combining MNX1 with clinical factors could well predict 1-, 2-, and 3-year OS probabilities in LUAD. Additionally, abnormally activated MNX1 promoted LUAD cell proliferation, invasion, and migration and inhibited apoptosis. MNX1 expression was higher in EGFR-mutant LUAD cells and correlated with osimertinib resistance. The combination of MNX1 depletion and osimertinib suppressed LUAD cell growth and proliferation, inhibited xenograft tumor growth, and reversed osimertinib resistance in vivo. Abnormally activated MNX1 affected PD-L1 expression and induced epithelial-mesenchymal transition (EMT), reversing osimertinib resistance in LUAD cells via the EGFR signaling pathway.
Conclusion: This study demonstrated that abnormally activated MNX1 promoted LUAD cell growth and proliferation and acquired resistance to osimertinib through AKT-mediated EMT and PD-L1. Therefore, MNX1 may be a promising prognostic biomarker and therapeutic target for osimertinib resistance in EGFR-mutant LUAD.
Keywords: lung adenocarcinoma, motor neuron and pancreas homeobox 1, EGFR, osimertinib
1Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Oncology, Gaoxin Branch of the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Nanchang Key Laboratory of Tumor Gene Diagnosis and Innovative Treatment Research, Nanchang, Jiangxi, People’s Republic of China; 4Jiangxi Provincial Key Laboratory of Oral Diseases, Department of Stomatology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Feng Qiu, Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yong Wai Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Email ndyfy01149@ncu.edu.cn Qingkun Jiang, Jiangxi Provincial Key Laboratory of Oral Diseases, Department of Stomatology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yong Wai Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Email ndyfy10001@ncu.edu.cn
Background: Bypass signaling plays an important role in mediating osimertinib resistance in lung adenocarcinoma (LUAD) with epidermal growth factor receptor (EGFR) mutations; however, the role of abnormally activated motor neuron and pancreas homeobox 1 (MNX1) in mediating osimertinib resistance in EGFR-mutant LUAD is unknown.
Methods: Bioinformatics and immunohistochemistry(IHC) analysis identified the MNX1 expression levels in LUAD. The effects of MNX1 and osimertinib on LUAD cell proliferation, invasion, migration, and apoptosis were evaluated using the cell counting kit-8, scratch, EdU, chamber transwell, and flow cytometry assays in vitro. In vivo, the effect of MNX1 expression on tumorigenicity was evaluated using subcutaneous transplanted tumors in nude mice.
Results: Bioinformatics databases and tumor tissue analysis revealed elevated MNX1 expression in LUAD tumor tissues, with high MNX1 expression correlating with poor prognosis. The receiver-operating characteristic(ROC) curve demonstrated that MNX1 has high specificity and sensitivity in diagnosing LUAD from the TCGA dataset. Multivariable COX analysis identified MNX1 as independent prognostic factors for overall survival (OS) in LUAD. Nomogram and calibration plots indicated that combining MNX1 with clinical factors could well predict 1-, 2-, and 3-year OS probabilities in LUAD. Additionally, abnormally activated MNX1 promoted LUAD cell proliferation, invasion, and migration and inhibited apoptosis. MNX1 expression was higher in EGFR-mutant LUAD cells and correlated with osimertinib resistance. The combination of MNX1 depletion and osimertinib suppressed LUAD cell growth and proliferation, inhibited xenograft tumor growth, and reversed osimertinib resistance in vivo. Abnormally activated MNX1 affected PD-L1 expression and induced epithelial-mesenchymal transition (EMT), reversing osimertinib resistance in LUAD cells via the EGFR signaling pathway.
Conclusion: This study demonstrated that abnormally activated MNX1 promoted LUAD cell growth and proliferation and acquired resistance to osimertinib through AKT-mediated EMT and PD-L1. Therefore, MNX1 may be a promising prognostic biomarker and therapeutic target for osimertinib resistance in EGFR-mutant LUAD.
Keywords: lung adenocarcinoma, motor neuron and pancreas homeobox 1, EGFR, osimertinib