Prognostic Significance of Methyl-CpG Binding Domain4 Polymorphism rs140693 and Clinical Characteristics in Chinese Lung Cancer Patients

Zhengxing Li; Yuewen Hu; Chang Xu; Zixiu Zou; Zhenyu Sun; Zhunyi Gao; Man Xiao; Shicheng Guo; Yi Wang; Haijian Wang; Zhiping Wang; Qiang Li; Bo Shen; Yuanlin Song; Junjie Wu

doi:10.1007/s43657-024-00171-z

Prognostic Significance of Methyl-CpG Binding Domain4 Polymorphism rs140693 and Clinical Characteristics in Chinese Lung Cancer Patients

Phenomics. 2024 Oct 8;4(5):453-464. doi: 10.1007/s43657-024-00171-z. eCollection 2024 Oct.

Authors

Zhengxing Li^#^{1

2}, Yuewen Hu^#², Chang Xu^#³, Zixiu Zou⁴, Zhenyu Sun⁵, Zhunyi Gao⁶, Man Xiao⁷, Shicheng Guo⁸, Yi Wang⁸, Haijian Wang⁸, Zhiping Wang⁹, Qiang Li¹⁰, Bo Shen^{11

12}, Yuanlin Song¹³, Junjie Wu^{13

14}

Affiliations

¹ Department of Surgery, Navy Military Medical University Affiliated to Changhai Hospital, Shanghai, 200433 China.
² Department of Outpatient, Chinese People's Liberation Army 92914 Army Hospital, Hainan, 571833 China.
³ Clinical College of Xiangnan University, Chenzhou, 423000 China.
⁴ School of Life Sciences, Fudan University, Shanghai, 200438 China.
⁵ School of Basic Medicine, Navy Military Medical University, Shanghai, 200433 China.
⁶ Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006 China.
⁷ Department of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, 571199 China.
⁸ State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200438 China.
⁹ Health Management Center, the First Affiliated Hospital of Navy Medical University, Shanghai, 200433 China.
¹⁰ Department of Respiratory and Critical Care Medicine, Shanghai East Hospital, TongJi University, Shanghai, 200120 China.
¹¹ The Affilated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, 42 Baiziting, Nanjing, Jiangsu 210009 China.
¹² Department of Oncology, The Dongtai Hospital of Nantong University, Dongtai, 224200 China.
¹³ Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032 China.
¹⁴ Department of Pulmonary and Critical Care Medicine, Shanghai Geriatric Medical Center, Shanghai, 201104 China.

^# Contributed equally.

PMID: 39723225
PMCID: PMC11666875 (available on 2025-10-01)
DOI: 10.1007/s43657-024-00171-z

Abstract

Lung cancer remains the leading cause of death among cancer patients, and the five-year survival rate is less than 25%. However, Methyl-CpG Binding Domain (MBD)4 polymorphism rs140693 predicts the prognosis of lung cancer patients still needs further verification. Primary lung cancer patients (n = 839) were collected from two hospitals, genomic DNA was extracted from blood, and genotyping was performed using SNPcan technology. Kaplan-Meier technique and multivariate Cox proportional hazards model were used to analyze the prognosis association between MBD4 and clinical characteristics. Significantly conferred a poorer prognosis was associated with the CT genotype (CT vs. CC; adjusted hazard ratio [HR] = 1.21, 95% CI: 1.03-1.43, p = 0.023) and dominant CT + TT genotype (CT + TT vs. CC; HR = 1.19, 95% CI: 1.02-1.39, p = 0.029) of MBD4 polymorphism rs140693 for all lung cancer patients, compared with the CC genotype. Stratified analysis showed that polymorphism rs140693 CT and dominant CT + TT genotype conferred a significantly poorer prognosis in female and lung adenocarcinoma (ADC) cancer patients, compared with the CC genotype. Non-small cell lung cancer (NSCLC) patients with the CT genotype had a poorer prognosis than those with the CC genotype. Additionally, the allele T of small cell lung cancer (SCLC) patients compared with the allele C was associated with a poor prognosis, and the CT and recessive TT genotype of SCLC patients conferred a significantly poor prognosis. The MBD4 polymorphism rs140693 is a significant prognostic genetic marker for predicting the prognosis of lung cancer patients.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00171-z.

Keywords: Lung cancer; Methyl-CpG Binding Domain4; Polymorphism; Prognosis; rs140693.

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