Weighted Gene Co-expression Network Analysis in Identification of Endometrial Cancer Prognosis Markers

Xiao-Lu Zhu,Yan-Li Xu,Juan Wang,Zhi-Hong Ai,Yin-Cheng Teng

doi:10.7314/apjcp.2012.13.9.4607

Xiao-Lu Zhu, Yan-Li Xu + Show 3 more

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https://doi.org/10.7314/apjcp.2012.13.9.4607

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Journal: Asian Pacific Journal of Cancer Prevention	Publication Date: Sep 30, 2012
Citations: 62	License type: cc-by

Abstract

Endometrial cancer (EC) is the most common gynecologic malignancy. Identification of potential biomarkers of EC would be helpful for the detection and monitoring of malignancy, improving clinical outcomes. The Weighted Gene Co-expression Network Analysis method was used to identify prognostic markers for EC in this study. Moreover, underlying molecular mechanisms were characterized by KEGG pathway enrichment and transcriptional regulation analyses. Seven gene co-expression modules were obtained, but only the turquoise module was positively related with EC stage. Among the genes in the turquoise module, COL5A2 (collagen, type V, alpha 2) could be regulated by PBX (pre-B-cell leukemia homeobox 1)1/2 and HOXB1(homeobox B1) transcription factors to be involved in the focal adhesion pathway; CENP-E (centromere protein E, 312kDa) by E2F4 (E2F transcription factor 4, p107/p130-binding); MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived [avian]) by PAX5 (paired box 5); and BCL-2 (B-cell CLL/ lymphoma 2) and IGFBP-6 (insulin-like growth factor binding protein 6) by GLI1. They were predicted to be associated with EC progression via Hedgehog signaling and other cancer related-pathways. These data on transcriptional regulation may provide a better understanding of molecular mechanisms and clues to potential therapeutic targets in the treatment of EC.

Highlights

Endometrial cancer (EC) is one of the most prevalent gynecologic malignancies and there are an estimated 40,000 new cases diagnosed in the United States (Jemal et al, 2009)
Among the genes in the turquoise module, COL5A2 could be regulated by PBX1/2 and HOXB1(homeobox B1) transcription factors to be involved in the focal adhesion pathway; CENP-E by E2F4 (E2F transcription factor 4, p107/p130-binding); MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived [avian]) by PAX5; and BCL-2 (B-cell CLL/ lymphoma 2) and IGF binding proteins (IGFBPs)-6 by GLI1
Our study explored several gene co-expression modules in EC progression

Summary

Introduction

Endometrial cancer (EC) is one of the most prevalent gynecologic malignancies and there are an estimated 40,000 new cases diagnosed in the United States (Jemal et al, 2009). Most patients (approximately 80%) are diagnosed with type I EC, low stage and grade, endometrioid histology, generally with a good prognosis (Rose, 1996; Tolentino Silva et al, 2012). Outcomes are extremely poor for patients with type II EC because of high stage and grade, non-endometrioid histology (Bokhman, 1983; Ray and Fleming, 2009). Weighted Gene Co-expression Network Analysis (WGCNA) constructs gene sets (modules) from the observed gene expression data These modules are related to gene ontology information to study their biological plausibility and to eliminate spurious modules due to technical artifacts (Horvath and Dong, 2008). We applied the same strategy to identify more prognosis markers for EC We characterized their underlying molecular mechanisms by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and transcriptional regulation analysis

Materials and Methods

Findings

Discussion