Opting for Local Region in SHOX2 Promoter as a DNA Methylation Biomarker for Lung Cancer Diagnosis
Main Article Content
Abstract
Epigenetic alterations play a main role in the initiation and progression of lung cancer. CpG methylation in the promoter of the Short Stature Homeobox 2 (SHOX2) gene has been evaluated and validated at different stages of this malignant disease. Several approaches for measuring DNA methylation have been established, including quantitative methylation-specific PCR (qMSP). This is a simple, fast, and cost-effective technique that can be easily applied to clinical practice. In this study, formalin-fixed, paraffin-embedded (FFPE) tissue samples were collected from 30 lung cancer patients and 30 patients suffering from non-cancerous pulmonary diseases. The methylation level of SHOX2 was evaluated in two CpG-riched regions by using qMSP and one of them could be conferred as a potential biomarker to lung cancer.
Keywords:
DNA methylation, SHOX2, lung cancer, quantitative methylation-specific PCR (qMSP)
References
L. E. Blake, et al., A comparison of gene expression and DNA methylation patterns across tissues and species, Genome Res, Vol. 30, No. 2, 2020, pp. 250-262, DOI: 10.1101/gr.254904.119.
[2] S. B. Baylin, DNA methylation and gene silencing in cancer, Nat Clin Pract Oncol, Vol. 2, No. S1, 2005, pp. S4-11, DOI: 10.1038/ncponc0354.
[3] G. Malpeli, et al., Methylation Dynamics of RASSF1A and Its Impact on Cancer, Cancers (Basel), Vol. 11, No. 7, 2019, DOI: 10.3390/cancers11070959.
[4] W. J. Locke, et al., DNA Methylation Cancer Biomarkers: Translation to the Clinic, Front Genet, Vol. 10, No., 2019, pp. 1150, DOI: 10.3389/fgene.2019.01150.
[5] H. Kim, X. Wang, and P. Jin, Developing DNA methylation-based diagnostic biomarkers, J Genet Genomics, Vol. 45, No. 2, 2018, pp. 87-97, DOI: 10.1016/j.jgg.2018.02.003.
[6] O. Taryma-Lesniak, K. E. Sokolowska, and T. K. Wojdacz, Current status of development of methylation biomarkers for in vitro diagnostic IVD applications, Clin Epigenetics, Vol. 12, No. 1, 2020, pp. 100, DOI: 10.1186/s13148-020-00886-6.
[7] H. Sung, et al., Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CA Cancer J Clin, Vol. 71, No. 3, 2021, pp. 209-249, DOI: 10.3322/caac.21660.
[8] R. Fang, et al., The Evaluation of Serum Biomarkers for Non-small Cell Lung Cancer (NSCLC) Diagnosis, Front Physiol, Vol. 9, No., 2018, pp. 1710, DOI: 10.3389/fphys.2018.01710.
[9] Y. X. Shi, et al., Current Landscape of Epigenetics in Lung Cancer: Focus on the Mechanism and Application, J Oncol, Vol. 2019, No., 2019, pp. 8107318, DOI: 10.1155/2019/8107318.
[10] D. Dietrich, et al., Development and performance evaluation of a CE-IVD for measuring SHOX2 DNA methylation in bronchial aspirates for the diagnosis of lung cancer, Lung Cancer, Vol. 77, No., 2012, pp. S22, DOI: 10.1016/j.lungcan.2012.05.036.
[11] S. M. Nguyen, et al., Projecting Cancer Incidence for 2025 in the 2 Largest Populated Cities in Vietnam, Cancer Control, Vol. 26, No. 1, 2019, pp. 1073274819865274, DOI: 10.1177/1073274819865274.
[12] J. Dimberg, et al., Analysis of APC and IGFBP7 promoter gene methylation in Swedish and Vietnamese colorectal cancer patients, Oncol Lett, Vol. 5, No. 1, 2013, pp. 25-30, DOI: 10.3892/ol.2012.967.
[13] P. K. Truong, et al., BRCA1 promoter hypermethylation signature for early detection of breast cancer in the Vietnamese population, Asian Pac J Cancer Prev, Vol. 15, No. 22, 2014, pp. 9607-10, DOI: 10.7314/apjcp.2014.15.22.9607.
[14] E. Khodadadi, et al., Current Advances in DNA Methylation Analysis Methods, Biomed Res Int, Vol. 2021, No., 2021, pp. 8827516, DOI: 10.1155/2021/8827516.
[15] S. J. Clark, et al., High sensitivity mapping of methylated cytosines, Nucleic Acids Res, Vol. 22, No. 15, 1994, pp. 2990-7, DOI: 10.1093/nar/22.15.2990.
[16] K. J. Livak and T. D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method, Methods, Vol. 25, No. 4, 2001, pp. 402-8, DOI: 10.1006/meth.2001.1262.
[17] N. Li, Y. Zeng, and J. Huang, Signaling pathways and clinical application of RASSF1A and SHOX2 in lung cancer, J Cancer Res Clin Oncol, Vol. 146, No. 6, 2020, pp. 1379-1393, DOI: 10.1007/s00432-020-03188-9.
[18] M. Guo, et al., Epigenetic heterogeneity in cancer, Biomark Res, Vol. 7, No., 2019, pp. 23, DOI: 10.1186/s40364-019-0174-y.
[19] R. Wasserkort, et al., Aberrant septin 9 DNA methylation in colorectal cancer is restricted to a single CpG island, BMC Cancer, Vol. 13, No., 2013, pp. 398, DOI: 10.1186/1471-2407-13-398.
[2] S. B. Baylin, DNA methylation and gene silencing in cancer, Nat Clin Pract Oncol, Vol. 2, No. S1, 2005, pp. S4-11, DOI: 10.1038/ncponc0354.
[3] G. Malpeli, et al., Methylation Dynamics of RASSF1A and Its Impact on Cancer, Cancers (Basel), Vol. 11, No. 7, 2019, DOI: 10.3390/cancers11070959.
[4] W. J. Locke, et al., DNA Methylation Cancer Biomarkers: Translation to the Clinic, Front Genet, Vol. 10, No., 2019, pp. 1150, DOI: 10.3389/fgene.2019.01150.
[5] H. Kim, X. Wang, and P. Jin, Developing DNA methylation-based diagnostic biomarkers, J Genet Genomics, Vol. 45, No. 2, 2018, pp. 87-97, DOI: 10.1016/j.jgg.2018.02.003.
[6] O. Taryma-Lesniak, K. E. Sokolowska, and T. K. Wojdacz, Current status of development of methylation biomarkers for in vitro diagnostic IVD applications, Clin Epigenetics, Vol. 12, No. 1, 2020, pp. 100, DOI: 10.1186/s13148-020-00886-6.
[7] H. Sung, et al., Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CA Cancer J Clin, Vol. 71, No. 3, 2021, pp. 209-249, DOI: 10.3322/caac.21660.
[8] R. Fang, et al., The Evaluation of Serum Biomarkers for Non-small Cell Lung Cancer (NSCLC) Diagnosis, Front Physiol, Vol. 9, No., 2018, pp. 1710, DOI: 10.3389/fphys.2018.01710.
[9] Y. X. Shi, et al., Current Landscape of Epigenetics in Lung Cancer: Focus on the Mechanism and Application, J Oncol, Vol. 2019, No., 2019, pp. 8107318, DOI: 10.1155/2019/8107318.
[10] D. Dietrich, et al., Development and performance evaluation of a CE-IVD for measuring SHOX2 DNA methylation in bronchial aspirates for the diagnosis of lung cancer, Lung Cancer, Vol. 77, No., 2012, pp. S22, DOI: 10.1016/j.lungcan.2012.05.036.
[11] S. M. Nguyen, et al., Projecting Cancer Incidence for 2025 in the 2 Largest Populated Cities in Vietnam, Cancer Control, Vol. 26, No. 1, 2019, pp. 1073274819865274, DOI: 10.1177/1073274819865274.
[12] J. Dimberg, et al., Analysis of APC and IGFBP7 promoter gene methylation in Swedish and Vietnamese colorectal cancer patients, Oncol Lett, Vol. 5, No. 1, 2013, pp. 25-30, DOI: 10.3892/ol.2012.967.
[13] P. K. Truong, et al., BRCA1 promoter hypermethylation signature for early detection of breast cancer in the Vietnamese population, Asian Pac J Cancer Prev, Vol. 15, No. 22, 2014, pp. 9607-10, DOI: 10.7314/apjcp.2014.15.22.9607.
[14] E. Khodadadi, et al., Current Advances in DNA Methylation Analysis Methods, Biomed Res Int, Vol. 2021, No., 2021, pp. 8827516, DOI: 10.1155/2021/8827516.
[15] S. J. Clark, et al., High sensitivity mapping of methylated cytosines, Nucleic Acids Res, Vol. 22, No. 15, 1994, pp. 2990-7, DOI: 10.1093/nar/22.15.2990.
[16] K. J. Livak and T. D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method, Methods, Vol. 25, No. 4, 2001, pp. 402-8, DOI: 10.1006/meth.2001.1262.
[17] N. Li, Y. Zeng, and J. Huang, Signaling pathways and clinical application of RASSF1A and SHOX2 in lung cancer, J Cancer Res Clin Oncol, Vol. 146, No. 6, 2020, pp. 1379-1393, DOI: 10.1007/s00432-020-03188-9.
[18] M. Guo, et al., Epigenetic heterogeneity in cancer, Biomark Res, Vol. 7, No., 2019, pp. 23, DOI: 10.1186/s40364-019-0174-y.
[19] R. Wasserkort, et al., Aberrant septin 9 DNA methylation in colorectal cancer is restricted to a single CpG island, BMC Cancer, Vol. 13, No., 2013, pp. 398, DOI: 10.1186/1471-2407-13-398.