iScience (Jul 2023)

Whole-genome DNA methylation and DNA methylation-based biomarkers in lung squamous cell carcinoma

  • Qidong Cai,
  • Boxue He,
  • Guangxu Tu,
  • Weilin Peng,
  • Shuai Shi,
  • Banglun Qian,
  • Qingchun Liang,
  • Shaoliang Peng,
  • Yongguang Tao,
  • Xiang Wang

Journal volume & issue
Vol. 26, no. 7
p. 107013

Abstract

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Summary: Exploring early detection methods through comprehensive evaluation of DNA methylation for lung squamous cell carcinoma (LUSC) patients is of great significance. By using different machine learning algorithms for feature selection and model construction based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, five methylation biomarkers in LUSC (along with mapped genes) were identified including cg14823851 (TBX4), cg02772121 (TRIM15), cg10424681 (C6orf201), cg12910906 (ARHGEF4), and cg20181079 (OR4D11), achieving extremely high sensitivity and specificity in distinguishing LUSC from normal samples in independent cohorts. Pyrosequencing assay verified DNA methylation levels, meanwhile qRT-PCR and immunohistochemistry results presented their accordant methylation-related gene expression statuses in paired LUSC and normal lung tissues. The five methylation-based biomarkers proposed in this study have great potential for the diagnosis of LUSC and could guide studies in methylation-regulated tumor development and progression.

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