Co-Expression Network Analysis Identified Gene Signatures in Osteosarcoma as a Predictive Tool for Lung Metastasis and Survival

Abstract

Osteosarcoma (OS) is the most common primary bone tumor, whose poor prognosis is mainly due to lung metastasis. The aim of this study is to build a practical and valid diagnostic test that can predict the risk of OS metastasis and progression. We performed weighted gene co-expression network analysis (WGCNA) on GSE21257 from the Gene Expression Omnibus (GEO) database, which contains microarray data of biopsies from OS patients. In these modules, the highest association was found between the blue module and metastasis stage (r = -0.52) by Pearson's correlation analysis. Based on Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, we derived eight clinically significant genes and constructed an eight-gene signature for metastasis status. It showed great efficacy to distinguish metastasis from non-metastasis (AUC = 0.886) and the results were validated in The Cancer Genome Atlas (TCGA) database. Functional enrichment analysis of hub genes showed that their biological processes focused on immune-related pathways, suggesting the important roles of immune cells, immune pathways and the tumor microenvironment in metastasis development. In conclusion, we discovered an efficient gene signature with great efficacy to distinguish metastasis status, which may help improve early diagnosis and treatment, enhancing the clinical outcomes of OS patients. Besides we created an effective protocol to seek for several hub genes in high-throughput data by combining WGCNA and LASSO Cox regression.

Identification and validation of key modules and hub genes associated with the pathological stage of oral squamous cell carcinoma by weighted gene co-expression network analysis

“…WGCNA is a powerful tool for analysing multiple genes in large-scale datasets. It has been extensively used to explore gene co-expression modules and hub genes as potential target biomarkers in many cancers (Foroughi et al, 2018;Chen et al, 2018;Giulietti et al, 2016;Liu et al, 2019;Wang et al, 2019a;Wang et al, 2019b;Xu et al, 2018;Zhai et al, 2019;Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c). In the current study, we applied WGCNA and systematically identified the turquoise module as the most significantly negatively associated (r = −0.2, P = 4e−04) with pathologic stage for the first time.…”

“…Another study (Ding et al, 2019) have also reported that the pseudopodium-enriched atypical kinase 1-PPP1R12B axis inhibits colorectal tumourigenesis and metastasis through the deactivation of the Grb2/PI3K/Akt pathway, which might provide a novel therapeutic strategy for CRC treatment. The hub gene CFD was identified and validated as a potential target gene in papillary thyroid cancer (Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c). CRYAB is a very important protein involved in a variety of signal transduction pathways, including apoptosis, inflammation and oxidative stress (Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c).…”

“…The hub gene CFD was identified and validated as a potential target gene in papillary thyroid cancer (Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c). CRYAB is a very important protein involved in a variety of signal transduction pathways, including apoptosis, inflammation and oxidative stress (Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c). CRYAB is a member of the small heat shock protein family (Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c), and many studies have confirmed that CRYAB plays an important role in a variety of tumours, such as OSCC (Annertz et al, 2014), colorectal cancer (Li et al, 2017), breast cancer (Kim et al, 2011), and hepatocellular carcinoma (Tang et al, 2009).…”

“…CRYAB is a very important protein involved in a variety of signal transduction pathways, including apoptosis, inflammation and oxidative stress (Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c). CRYAB is a member of the small heat shock protein family (Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c), and many studies have confirmed that CRYAB plays an important role in a variety of tumours, such as OSCC (Annertz et al, 2014), colorectal cancer (Li et al, 2017), breast cancer (Kim et al, 2011), and hepatocellular carcinoma (Tang et al, 2009). One study (Wojtas et al, 2017) confirmed that the differential expression of FAM189A2 can serve as a gene expression marker in thyroid tumours.…”

“…Weighted gene co-expression network analysis (WGCNA) is an efficient systematic biological approach that can highlight co-expressed gene modules and investigate the relationships between gene modules and phenotypes more effectively (Langfelder & Horvath, 2008). WGCNA has been successfully and comprehensively used to explore targeted modules and hub genes in cancer-related research, such as clear cell renal cell carcinoma (Wang et al, 2019a;Wang et al, 2019b) and pancreatic carcinoma (Zhou et al, 2018a;Zhou et al, 2018b).…”