Predicting the Lung Squamous Cell Carcinoma Diagnosis and Prognosis Markers by Unique DNA Methylation and Gene Expression Profiles

J Comput Biol. 2020 Jul;27(7):1041-1054. doi: 10.1089/cmb.2019.0138. Epub 2019 Nov 11.

Abstract

The early diagnosis of lung squamous cell carcinoma (LUSC) is difficult, causing an unsatisfactory prognosis. Therefore, the 5-year survival rate of LUSC is poor. This study aimed at screening the potential diagnostic and prognostic markers for LUSC. The data of LUSC gene expression profiles and DNA methylation were obtained from The Cancer Genome Atlas (TCGA) database; the differentially expressed genes (DEGs) and the differentially methylated genes (DMGs) were screened out by an independent t-test and Benjamini/Hochberg methods. Further, the classifiers of the gene expression and DNA methylation markers in LUSC were constructed. After that, diagnostic and prognostic markers in LUSC were analyzed by the protein-protein interaction (PPI) network. The DEGs and the DMGs from TCGA database of LUSC were screened out. After strict filtration, we identified three potential DMGs (POU domain, class 4, transcription factor 2 [POU4F2], EN1, single-minded homolog 1 [SIM1]) for early diagnosis and seven potential DEGs (G-protein coupled receptor 78 [GPR78], PCDHA5, myosin binding protein H [MYBPH], RTL3, KIAA0408, HSD3B2, PCDHA12) for prognosis of LUSC. The tumor-normal tissue classification model and prognosis model were validated in two independent datasets. In addition, the PPI network was constructed, including three DMGs and the five DEGs (GPR78, MYBPH, KIAA0408, HSD3B2, PCDHA12) of the seven DEGs. The potential DMGs (POU4F2, EN1, SIM1) and DEGs (GPR78, MYBPH, KIAA0408, HSD3B2, PCDHA12) for the diagnosis and prognosis of LUSC identified in this article are expected to be further applied in clinical practice of the treatment of LUSC.

Keywords: differentially expressed genes; differentially methylated genes; lung squamous cell carcinoma; protein-protein interaction network.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • DNA Methylation*
  • Endoplasmic Reticulum Chaperone BiP
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Prognosis
  • Protein Interaction Maps

Substances

  • Biomarkers, Tumor
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human