Identification of candidate genes or microRNAs associated with the lymph node metastasis of SCLC

Zhonghao Wang,Bei Lu,Xi Yan,Lixin Sun,Jinzhi Xu

doi:10.1186/s12935-018-0653-5

Abstract

BackgroundSmall cell lung cancer (SCLC) is a highly malignant cancer, and over 70% of patients with SCLC present with the metastatic disease. We aimed to explore some novel differentially expressed genes (DEGs) or microRNAs (miRNAs) associated with the lymph node metastasis of SCLC.MethodsThe DEGs between the metastasis and cancer groups were identified, and GO functional and KEGG pathway enrichment analyses for these DEGs were implemented. Subsequently, the protein–protein interaction network and subnetwork of module were constructed. Then the regulatory networks based on miRNAs, transcription factors (TFs) and target DEGs were constructed. Ultimately, the survival analysis for DEGs was performed to obtain the DEGs related to the survival of SCLC.ResultsHere, 186 upregulated (e.g., GSR, HCP5) and 144 downregulated DEGs (e.g., MET, GRM8, and DACH1) were identified between the SCLC patients with lymph node metastasis and without lymph node metastasis. GRM8 was attracted to the G-protein coupled receptor signaling pathway. Besides, miR-126 was identified in the miRNAs-TFs-target regulatory network. GRM8 and DACH1 were all regulated by miR-126. In particular, GSR and HCP5 were correlated with survival of SCLC patients.ConclusionMiR-126, DACH1, GRM8, MET, GSR, and HCP5 were implicated in the lymph node metastasis process of SCLC.

Highlights

Small cell lung cancer (SCLC) is a highly malignant cancer, and over 70% of patients with SCLC present with the metastatic disease
Our results presented that the expressions of MET proto-oncogene, receptor tyrosine kinase (MET), glutamate metabotropic receptor 8 (GRM8), cholinergic receptor nicotinic alpha 5 subunit (CHRNA5), and dachshund family transcription factor 1 (DACH1) were reduced in the SCLC patients with lymph node metastasis compared with those patients without lymph node metastasis
Functional and pathways enrichment analyses The enriched functions for upregulated differentially expressed genes (DEGs) were listed in Table 1a, such as kidney development (GO_BP; p value = 1.89 × 10−4), extracellular region (GO_CC; p value = 1.72 × 10−4), and calcium ion binding (GO_MF; p value = 2.70 × 10−4)

Summary

Introduction

Small cell lung cancer (SCLC) is a highly malignant cancer, and over 70% of patients with SCLC present with the metastatic disease. We aimed to explore some novel differentially expressed genes (DEGs) or microRNAs (miRNAs) associated with the lymph node metastasis of SCLC. SCLC, a poorly differentiated and aggressive type of LC, presents an early metastases, fleetly growth rate, and poor prognosis with a lower. The central trafficking hubs for recirculating immune cells, are widely present throughout the body [9]. Tumor cells could migrate into the lymph nodes and rapidly spread to other organs [10]. Activator protein-1 (AP-1), a transcription factor (TF), regulates the gene expression in response to various stimulus [11]. The abnormal expression of genes regulated by AP-1 was involved in the process of lymphatic metastasis. Previous studies found that the overexpressions of urokinase type plasminogen

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