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. 2021 Jan 30;12(7):1867-1883.
doi: 10.7150/jca.48979. eCollection 2021.

Screening and bioinformatical analysis of differentially expressed genes in nasopharyngeal carcinoma

Weiqian Guo  1 , Xiaomin Zheng  1 , Lei Hua  1 , Xianbin Zheng  2 , Yangyang Zhang  3 , Bin Sun  3 , Zhenchao Tao  3 , Jin Gao  1   3
Affiliations

Screening and bioinformatical analysis of differentially expressed genes in nasopharyngeal carcinoma

Weiqian Guo et al. J Cancer. .

Abstract

Objective: To identify differentially expressed genes via bioinformatical analysis for nasopharyngeal carcinoma (NPC) and explore potential biomarkers for NPC. Methods: We downloaded the NPC gene expression datasets (GSE40290, GSE53819) and obtained differentially expressed genes (DEGs) via GEO2R. Functional analysis of DEGs was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In order to explore the interaction of DEGs and screen the core genes, we established protein-protein interaction (PPI) network. Then the expression level, prognostic and diagnostic analysis of the core genes in NPC were performed to reveal their potential effects on NPC. Furthermore, we obtained the transcription factors (TF) and microRNAs of core genes to construct the coregulatory network. Results: We obtained 124 up-regulated genes and 190 down-regulated genes in total. These genes were found to be related to signal transduction, extracellular matrix organization and cell adhesion based on GO analysis. KEGG analysis revealed that the NF-kappa B (NF-κB) signaling pathway, pathways in cancer were mainly enriched signaling pathways. 25 core genes were obtained by constructing PPI network. Then the high expression of 10 core genes in NPC were verified via GEPIA, Oncomine databases and laboratory experiments. The TF-microRNA coregulatory network of the 10 core genes was built. Survival and diagnostic analysis indicated that SPP1 had negative influence on the prognosis of NPC patients based on two datasets and nine up-regulated core genes (FN1, MMP1, MMP3, PLAU, PLAUR, SERPINE1, SPP1, COL8A1, COL10A1) might be diagnostic markers for NPC. Conclusions: Core genes of NPC were screened out by bioinformatical analysis in the present study and these genes may serve as prognostic and diagnostic biomarkers for NPC.

Keywords: bioinformatical analysis; core genes; microarray; nasopharyngeal carcinoma; prognosis.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
DEGs of GSE40290 and GSE53819. Heatmap of the top 50 DEGs: (A) GSE40290; (C) GSE53819; Volcano map: (B) GSE40290; (D) GSE53819. Red: up-regulated DEGs, green: down-regulated DEGs, black: no difference.
Figure 2
Figure 2
314 commonly DEGs of GSE40290 and GSE53819. (A) 124 up-regulated DEGs; (B) 190 down-regulated DEGs.
Figure 3
Figure 3
Functional analysis of the 314 DEGs. (A) BP; (B) CC; (C) MF; (D) KEGG pathway analysis.
Figure 4
Figure 4
PPI network. (A) PPI network of the 314 DEGs; (B) Module analysis of the network. Red: up-regulated genes, yellow: down-regulated genes; (C) KEGG analysis of the 25 core genes in the module.
Figure 5
Figure 5
Significantly expressed 10 core genes in NPC tissues compared to normal tissues in GEPIA: (A) FN1; (B) MMP1; (C) MMP3; (D) PLAU; (E) PLAUR; (F) SERPINE1; (G) SPP1; (H) COL8A1; (I) COL10A1; (J) COL17A1. Red: tumor tissues, grey: normal tissues. *: P < 0.05.
Figure 6
Figure 6
Verification of the expression of the 10 core genes in NPC tissues compared to normal tissues in Oncomine: (A) FN1; (B) MMP1; (C) MMP3; (D) PLAU; (E) PLAUR; (F) SERPINE1; (G) SPP1; (H) COL8A1; (I) COL10A1; (J) COL17A1. The cut-off criterion of statistical significance was P < 0.05.
Figure 7
Figure 7
The expression of the 10 core genes in NPC cells (CNE1, CNE2, 6-10B, 5-8F) and normal nasopharyngeal cell (NP69). (A) qRT-PCR; (B) Western blot analysis. *: P < 0.05, **: P < 0.01, ***: P < 0.001, ****: P < 0.0001.
Figure 8
Figure 8
Genetic information of the 10 core genes. (A) Biological process (P < 0.01); (B) Genetic alterations in cBioPortal database; (C) Alteration frequency.
Figure 9
Figure 9
The construction of TF-microRNA coregulatory network. (A) Integrative regulatory network of TF-mRNA-microRNA; (B) Network after removing the points with only one degree of correlation; (C) The expression of key elements in TF-microRNA coregulatory network in NPC cells. Red: core genes, yellow: TFs, blue: microRNAs, *: P < 0.05, **: P < 0.01, ***: P < 0.001, ****: P < 0.0001.
Figure 10
Figure 10
The prognostic analysis of core genes in NPC based on GEPIA: (A) MMP1; (B) PLAU; (C) PLAUR; (D) SERPINE1; (E) SPP1. The cut-off criterion of statistical significance was P < 0.05.
Figure 11
Figure 11
The prognostic analysis (A) and diagnostic analysis (B) of core genes in NPC based on GSE102349 and GSE12452 datasets, respectively. The cut-off criterion of statistical significance was P < 0.05.
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