A network-based method for identifying prognostic gene modules in lung squamous carcinoma.

Lin Feng,Ning An,Lei Zhang,Guiqi Wang,Kaitai Zhang,Shujun Cheng,Xiaohong Liu,Run Tong

doi:10.18632/oncotarget.7632

Abstract

Similarities in gene expression between both developing embryonic and precancerous tissues and cancer tissues may help identify much-needed biomarkers and therapeutic targets in lung squamous carcinoma. In this study, human lung samples representing ten successive time points, from embryonic development to carcinogenesis, were used to construct global gene expression profiles. Differentially expressed genes with similar expression in precancerous and cancer samples were identified. Using a network-based greedy searching algorithm to analyze the training cohort (n = 69) and three independent testing cohorts, we successfully identified a significant 22-gene module in which expression levels were correlated with overall survival in lung squamous carcinoma patients.

Highlights

The initiation of lung squamous carcinoma (LSQC) is characterized by five major successive stages: normal bronchial epithelium, squamous metaplasia, mildmoderate dysplasia, severe dysplasia, and invasive carcinoma [1]
Using a network-based greedy searching algorithm to analyze the training cohort (n = 69) and three independent testing cohorts, we successfully identified a significant 22-gene module in which expression levels were correlated with overall survival in lung squamous carcinoma patients
We used 208 consistently down-regulated differentially expressed genes (DEGs) belonging to the GO term “immune response” and 234 consistently upregulated DEGs belonging to the GO term “cell cycle” for further analyses

Summary

Introduction

The initiation of lung squamous carcinoma (LSQC) is characterized by five major successive stages: normal bronchial epithelium, squamous metaplasia, mildmoderate dysplasia, severe dysplasia (carcinoma in situ), and invasive carcinoma [1]. Understanding the molecular alterations that occur during carcinogenesis, especially in precancerous stages, might aid in the discovery of prognostic biomarkers and identification of candidate therapeutic targets. The association between embryonic development and carcinogenesis has been widely documented, and some molecules are essential in both processes. Cancer gene expression profiles can recapitulate the expression patterns of embryonic development [12,13,14,15,16,17]. These findings suggest that tumors can be viewed as an aberrant organs which have acquired the capacity for indefinite proliferation through various genetic alterations [18]

Methods

Results

Conclusion