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SHOX2 methylation in Vietnamese patients with lung cancer

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Abstract

Background

DNA methylation on cytosine in the CpG dinucleotides is one of the most common epigenetic perturbations taking place during cancer initiation, progression, occurrence and resistance therapy. DNA methylation seems to be sufficiently stable epigenetic modification to be utilized as a cancer biomarker in in vitro diagnostic (IVD) settings. Nowadays, the SHOX2 methylation (mSHOX2) is one of the most valuable DNA methylation biomarkers of lung cancer that is the leading cause of cancer death. It is being continuously validated across ethnicities, lifestyles and lifespan. This study focused on characteristics of mSHOX2 in Vietnamese patients with lung cancer since a lack of investigation and evidence of its utility in this country.

Methods

The probe and primer sets were designed according to the MethyLight method for quantitative assessment of the mSHOX2 in 214 formalin-fixed paraffin-embedded (FFPE) lung tissues and 57 plasma samples.

Results

mSHOX2 in FFPE tissues allowed discriminating benign and malignant lung diseases with 60% (95% CI 50.7–68.8%) sensitivity and 90.4% (95% CI 82.6–95.5%) specificity. Importantly, based on mSHOX2 in plasma, lung cancer could be detected with 83.3% (95% CI 65.3–94.4%) sensitivity and 92.6% (95% CI 75.7–99.1%) specificity, respectively. There were insignificant associations between mSHOX2 with age, cancer stage, EGFR mutation and serum CEA, CYFRA21-1 concentrations except for that gender.

Conclusion

Our study indicated that mSHOX2 was satisfactory for distinguishing malignant from benign lung tissue and noninvasively detecting lung cancer.

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Acknowledgements

The authors would like to thank the Center for Life Science Research (VNU University of Science) for technical support.

Funding

This study was financially supported by Grant 108.01-2019.306 from the Ministry of Science and Technology, Viet Nam.

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Authors and Affiliations

  1. Faculty of Biology, University of Science, Vietnam National University, Hanoi, Vietnam

    Thi Thuong Lan Vo, Thuy Ngan Nguyen, Thu Trang Nguyen & Anh Thuy Duong Pham

  2. Pathology and Molecular Biology Center, Vietnam National Cancer Hospital, Hanoi, Vietnam

    Dieu Linh Vuong & Van To Ta

  3. Department of Chemistry, 175 Hospital, Ho Chi Minh City, Vietnam

    Van Son Ho

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Contributions

VTTL: Conceptualization, Funding Acquisition, Methodology, Project Administration, Supervision, Writing—review & editing. NTN and NTT: Investigation, Formal analysis. PATD: Data curation, Formal analysis. VDL, TVT and HVS: Resources.

Corresponding author

Correspondence to Thi Thuong Lan Vo.

Ethics declarations

Conflict of interest

The authors Vo Thi Thuong Lan, Nguyen Thuy Ngan, Nguyen Thuy Trang, Pham Anh Thuy Duong, Vuong Dieu Linh, Ta Van To and Ho Van Son declare that they have no conflict of interest.

Ethical approval

The study was performed in accordance with the ethical standards approved by the Ethics Committee of Vietnam Academy of Science and Technology (03-2020/NCHG-HDDD).

Informed consent

Informed written consents were obtained from healthy participants and patients included in the study.

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Supplementary Information

Below is the link to the electronic supplementary material.

11033_2022_7172_MOESM1_ESM.docx

Supplementary file1 (DOCX 216 KB) Supplementary Fig. 1. Nucleotide sequence of the SHOX2 promoter (NG_047079 positions 7750–7730) and position of MSP primers used for methylation analysis of SHOX2.1 and SHOX2.2 regions.

11033_2022_7172_MOESM2_ESM.docx

Supplementary file2 (DOCX 15 KB) Supplementary Table 1. Primer sets and probe, and quantitative real-time PCR conditions for measurement of the SHOX2 methylation.

11033_2022_7172_MOESM3_ESM.docx

Supplementary file3 (DOCX 14 KB) Supplementary Table 2. Specificity of primer sets used for amplification of the methylated SHOX2.

11033_2022_7172_MOESM4_ESM.docx

Supplementary file4 (DOCX 18 KB) Supplementary Table 3. Association of the SHOX2 methylation status with the clinicopathological characteristics.

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Vo, T.T.L., Nguyen, T.N., Nguyen, T.T. et al. SHOX2 methylation in Vietnamese patients with lung cancer. Mol Biol Rep 49, 3413–3421 (2022). https://doi.org/10.1007/s11033-022-07172-z

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