Identification of esophageal cancer pathway deviation and construction of a diagnosis model using three kernel genes

J Cell Physiol. 2019 Aug;234(10):18098-18110. doi: 10.1002/jcp.28442. Epub 2019 Mar 5.

Abstract

The purpose of this study is to better understand the role of interleukin 35 (IL35) in esophageal carcinoma by comparing the mRNA level in Barrett's esophageal mucosa and in matched normal squamous mucosa and to understand how the diagnosis model works with two other genes: hepatocyte nuclear factor 1B (HNF1B) and cAMP responsive element binding protein 3-like 1 (CREB3L1). By comparing carcinoma tissue and normal tissue samples, we extracted all the differentially expressed mRNAs. The bioinformatics analysis resulted in the discovery of three prominent genes. Eventually, the three genes were utilized to train a deep-learning model. An additional wet experiment was conducted to validate the effect of IL35. All the differentially expressed genes were enriched into nine groups, each of which has specific biological functions. Given that the three significant genes HNF1B, CREB3L1, and IL35 as diagnostic features, a deep-learning model was constructed, reaching an accuracy of 93% in the training set and 87% in the test set. Our findings suggest that IL35, along with the other two signatures, can distinguish esophageal tumor samples from normal samples precisely.

Keywords: diagnosis model; esophageal cancer; pathway deviation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Databases, Genetic
  • Deep Learning*
  • Early Detection of Cancer / methods*
  • Esophageal Neoplasms / diagnosis*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / therapy
  • Esophageal Squamous Cell Carcinoma / diagnosis*
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / mortality
  • Esophageal Squamous Cell Carcinoma / therapy
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Nuclear Factor 1-beta / genetics*
  • Humans
  • Interleukin-12 Subunit p35 / genetics*
  • Models, Genetic*
  • Nerve Tissue Proteins / genetics*
  • Predictive Value of Tests
  • Reproducibility of Results
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • CREB3L1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • HNF1B protein, human
  • IL12A protein, human
  • Interleukin-12 Subunit p35
  • Nerve Tissue Proteins
  • Hepatocyte Nuclear Factor 1-beta