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. 2021 Jan 6:2021:6696198.
doi: 10.1155/2021/6696198. eCollection 2021.

Identified GNGT1 and NMU as Combined Diagnosis Biomarker of Non-Small-Cell Lung Cancer Utilizing Bioinformatics and Logistic Regression

Jia-Jia Zhang  1 , Jiang Hong  2 , Yu-Shui Ma  3   4 , Yi Shi  4 , Dan-Dan Zhang  4 , Xiao-Li Yang  4 , Cheng-You Jia  1 , Yu-Zhen Yin  1 , Geng-Xi Jiang  2 , Da Fu  4 , Fei Yu  1
Affiliations

Identified GNGT1 and NMU as Combined Diagnosis Biomarker of Non-Small-Cell Lung Cancer Utilizing Bioinformatics and Logistic Regression

Jia-Jia Zhang et al. Dis Markers. .

Abstract

Non-small-cell lung cancer (NSCLC) is one of the most devastating diseases worldwide. The study is aimed at identifying reliable prognostic biomarkers and to improve understanding of cancer initiation and progression mechanisms. RNA-Seq data were downloaded from The Cancer Genome Atlas (TCGA) database. Subsequently, comprehensive bioinformatics analysis incorporating gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the protein-protein interaction (PPI) network was conducted to identify differentially expressed genes (DEGs) closely associated with NSCLC. Eight hub genes were screened out using Molecular Complex Detection (MCODE) and cytoHubba. The prognostic and diagnostic values of the hub genes were further confirmed by survival analysis and receiver operating characteristic (ROC) curve analysis. Hub genes were validated by other datasets, such as the Oncomine, Human Protein Atlas, and cBioPortal databases. Ultimately, logistic regression analysis was conducted to evaluate the diagnostic potential of the two identified biomarkers. Screening removed 1,411 DEGs, including 1,362 upregulated and 49 downregulated genes. Pathway enrichment analysis of the DEGs examined the Ras signaling pathway, alcoholism, and other factors. Ultimately, eight prioritized genes (GNGT1, GNG4, NMU, GCG, TAC1, GAST, GCGR1, and NPSR1) were identified as hub genes. High hub gene expression was significantly associated with worse overall survival in patients with NSCLC. The ROC curves showed that these hub genes had diagnostic value. The mRNA expressions of GNGT1 and NMU were low in the Oncomine database. Their protein expressions and genetic alterations were also revealed. Finally, logistic regression analysis indicated that combining the two biomarkers substantially improved the ability to discriminate NSCLC. GNGT1 and NMU identified in the current study may empower further discovery of the molecular mechanisms underlying NSCLC's initiation and progression.

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Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1
Figure 1
Identification of DEGs in NSCLC. (a) Workflow for the identification of key pathways and genes between non-small-cell lung cancer and normal samples. (b) DEGs between LUAD tissue and normal tissue. The volcano plot showed 1,411 DEGs. The red dots represented the upregulated genes, while the green dots represented downregulated genes. DEGs: differentially expressed genes. (c) Heatmap of the 20 upregulated and downregulated DEGs. The red color represents high expression, and the blue color represents low expression.
Figure 2
Figure 2
Functional and pathway analysis of DEGs. (a) GO and KEGG analysis of DEGs. P value is displayed on the x-axis, and GO function enrichment and KEGG pathway are shown on the y-axis. GO: gene ontology. KEGG: Kyoto Encyclopedia of Genes and Genomes. (b) The overlapping genes of different algorithms selected by cytoHubba. (c) The most significant modules obtained from the PPI network. PPI: protein-protein interaction.
Figure 3
Figure 3
The prognostic value of hub genes in NSCLC patients. Kaplan–Meier curve analysis between hub gene expression and prognosis in NSCLC patients from the KM plotter database.
Figure 4
Figure 4
The expression and prognostic value of four hub genes in NSCLC patients. (a) The ROC curves of hub genes. AUC and P values of each hub gene are displayed in the plot. ROC: receiver operating characteristic. AUC: area under the curve. (b) Expression levels of significant genes compared between different types of NSCLC and normal tissues from the Oncomine platform. Fold changes and P values of each hub gene are displayed in the plot. (c) Immunohistochemical analysis of GNGT1 and NMU in normal tissues and NSCLC tissues from the Human Protein Atlas.
Figure 5
Figure 5
The expression and prognostic value of GNGT1 and NMU in NSCLC patients. (a) Genetic alteration of GNGT1 and NMU genes in NSCLC patients. (b) Illustration of the alteration frequency of GNGT1 and NMU genes in NSCLC patients. (c) Coexpression between GNGT1 and NMU. (d) Overall survival analysis for GNGT1 and NMU genes in NSCLC patients. (e) Combined diagnosis of GNGT1 and NMU genes in NSCLC patients.
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