Identification of Lymph Node Metastasis-Related Key Genes and Prognostic Risk Model in Bladder Cancer by Co-Expression Analysis.

Cheng Luo,Yukun Wu,Lingwu Chen,Junxing Chen,Bin Huang,Yadong Xu,Wei Ou

doi:10.3389/fmolb.2021.633299

Abstract

Background: Lymph node metastasis (LNM) is an important pathological characteristic of bladder cancer (BCa). However, the molecular mechanism underlying LNM was not thoroughly elaborated. Identification for LNM-related biomarkers may contribute to making suitable therapies. So, the current study was aimed to identify key genes and construct a prognostic signature. Methods: Based on the Cancer Genome Atlas (TCGA) database, gene expression and clinical information were obtained. Then, the weighted gene co-expression network analysis (WGCNA) was performed to identify the key modules and hub genes. A function analysis and a gene set enrichment analysis were applied to explore biological functions and pathways of interested genes. Furthermore, a prognostic model based on LNM-related genes was constructed by using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Results: Finally, nine co-expression modules were constructed, and two modules (turquoise and green) were significantly associated with LNM. Three hub genes were identified as DACT3, TNS1, and MSRB3, which were annotated in actin binding, actin cytoskeleton, adaptive immune response, and cell adhesion molecular binding by the GSEA method. Further analysis demonstrated that three hub genes were associated with the overall survival of BCa patients. In addition, we built a prognostic signature based on the genes from LNM-related modules and evaluated the prognostic value of this signature. Conclusion: In general, this study revealed the key genes related to LNM and prognostic signature, which might provide new insights into therapeutic target of BCa.

Highlights

Bladder cancer (BCa) is the second most common malignancy of the genitourinary cancers (Siegel et al, 2019)
We aimed to identify hub genes associated with lymph node metastasis (LNM) in BCa and explore novel gene markers to build a prognostic model
2,660 differentially expressed genes (DEGs) associated with Lymph node metastasis (LNM) were identified and used for the construction of weighted co-expression network

Summary

Introduction

Bladder cancer (BCa) is the second most common malignancy of the genitourinary cancers (Siegel et al, 2019). 25% of BCa in patients are pathologically defined as muscle-invasive tumors. Pelvic lymph nodes are commonly the first site for metastasis of BCa (Witjes et al, 2020). Radical cystectomy with lymph node dissection is the standard treatment for these patients, of whom 18.0–30.4% harbored nodal metastasis (Youssef and Raj, 2011; Hautmann et al, 2012). Lymph Node Metastasis–Related Genes dissection provides accurate node staging and predictive information for oncologic outcomes except for the tumor stage and grade. Several parameters, based on the lymph node status including positive node count, lymph node density, and log odds, were proposed as prognostic factors for BCa patients (Fransen van de Putte et al, 2015; Masson-Lecomte et al, 2013; Lee et al, 2012; Jin et al, 2019). Lymph node metastasis (LNM) is an important pathological characteristic of bladder cancer (BCa). The current study was aimed to identify key genes and construct a prognostic signature

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