Identification of Hub Genes Associated With Development of Head and Neck Squamous Cell Carcinoma by Integrated Bioinformatics Analysis

Overview

Journal Front Oncol

Specialty Oncology

Date 2020 Jun 13

PMID 32528874

Citations 54

Authors

Chia Ying Li

Jia-Hua Cai

Jeffrey J P Tsai

Charles C N Wang

Affiliations

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Abstract

Improved insight into the molecular mechanisms of head and neck squamous cell carcinoma (HNSCC) is required to predict prognosis and develop a new therapeutic strategy for targeted genes. The aim of this study is to identify significant genes associated with HNSCC and to further analyze its prognostic significance. In our study, the cancer genome atlas (TCGA) HNSCC database and the gene expression profiles of GSE6631 from the Gene Expression Omnibus (GEO) were used to explore the differential co-expression genes in HNSCC compared with normal tissues. A total of 29 differential co-expression genes were screened out by Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis methods. As suggested in functional annotation analysis using the R clusterProfiler package, these genes were mainly enriched in epidermis development and differentiation (biological process), apical plasma membrane and cell-cell junction (cellular component), and enzyme inhibitor activity (molecular function). Furthermore, in a protein-protein interaction (PPI) network containing 21 nodes and 25 edges, the ten hub genes (S100A8, S100A9, IL1RN, CSTA, ANXA1, KRT4, TGM3, SCEL, PPL, and PSCA) were identified using the CytoHubba plugin of Cytoscape. The expression of the ten hub genes were all downregulated in HNSCC tissues compared with normal tissues. Based on survival analysis, the lower expression of CSTA was associated with worse overall survival (OS) in patients with HNSCC. Finally, the protein level of CSTA, which was validated by the Human Protein Atlas (HPA) database, was down-regulated consistently with mRNA levels in head and neck cancer samples. In summary, our study demonstrated that a survival-related gene is highly correlated with head and neck cancer development. Thus, CSTA may play important roles in the progression of head and neck cancer and serve as a potential biomarker for future diagnosis and treatment.

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References

Yang Y, Han L, Yuan Y, Li J, Hei N, Liang H . Gene co-expression network analysis reveals common system-level properties of prognostic genes across cancer types. Nat Commun. 2014; 5:3231. PMC: 3951205. DOI: 10.1038/ncomms4231. View

Chin C, Chen S, Wu H, Ho C, Ko M, Lin C . cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014; 8 Suppl 4:S11. PMC: 4290687. DOI: 10.1186/1752-0509-8-S4-S11. View

Strojan P, Budihna M, Smid L, Svetic B, Vrhovec I, Kos J . Prognostic significance of cysteine proteinases cathepsins B and L and their endogenous inhibitors stefins A and B in patients with squamous cell carcinoma of the head and neck. Clin Cancer Res. 2000; 6(3):1052-62. View

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

Ma Y, Chen Y, Li Y, Grun K, Berndt A, Zhou Z . Cystatin A suppresses tumor cell growth through inhibiting epithelial to mesenchymal transition in human lung cancer. Oncotarget. 2018; 9(18):14084-14098. PMC: 5865655. DOI: 10.18632/oncotarget.23505. View

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

Anicin A, Gale N, Smid L, Kos J, Strojan P . Expression of stefin A is of prognostic significance in squamous cell carcinoma of the head and neck. Eur Arch Otorhinolaryngol. 2013; 270(12):3143-51. DOI: 10.1007/s00405-013-2465-5. View

Robinson M, McCarthy D, Smyth G . edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2009; 26(1):139-40. PMC: 2796818. DOI: 10.1093/bioinformatics/btp616. View

Can T . Introduction to bioinformatics. Methods Mol Biol. 2013; 1107:51-71. DOI: 10.1007/978-1-62703-748-8_4. View

10.

Langfelder P, Horvath S . WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008; 9:559. PMC: 2631488. DOI: 10.1186/1471-2105-9-559. View

11.

Kos J, Lah T . Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer (review). Oncol Rep. 1998; 5(6):1349-61. DOI: 10.3892/or.5.6.1349. View

12.

Maity B, Sheff D, Fisher R . Immunostaining: detection of signaling protein location in tissues, cells and subcellular compartments. Methods Cell Biol. 2013; 113:81-105. DOI: 10.1016/B978-0-12-407239-8.00005-7. View

13.

Spitz M . Epidemiology and risk factors for head and neck cancer. Semin Oncol. 1994; 21(3):281-8. View

14.

Saris C, Horvath S, van Vught P, van Es M, Blauw H, Fuller T . Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients. BMC Genomics. 2009; 10:405. PMC: 2743717. DOI: 10.1186/1471-2164-10-405. View

15.

Li J, Zhou D, Qiu W, Shi Y, Yang J, Chen S . Application of Weighted Gene Co-expression Network Analysis for Data from Paired Design. Sci Rep. 2018; 8(1):622. PMC: 5766625. DOI: 10.1038/s41598-017-18705-z. View

16.

Gupta A, Nitoiu D, Brennan-Crispi D, Addya S, Riobo N, Kelsell D . Cell cycle- and cancer-associated gene networks activated by Dsg2: evidence of cystatin A deregulation and a potential role in cell-cell adhesion. PLoS One. 2015; 10(3):e0120091. PMC: 4364902. DOI: 10.1371/journal.pone.0120091. View

17.

DSouza G, Dempsey A . The role of HPV in head and neck cancer and review of the HPV vaccine. Prev Med. 2011; 53 Suppl 1:S5-S11. PMC: 3287051. DOI: 10.1016/j.ypmed.2011.08.001. View

18.

Tang Z, Kang B, Li C, Chen T, Zhang Z . GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019; 47(W1):W556-W560. PMC: 6602440. DOI: 10.1093/nar/gkz430. View

19.

Thul P, Lindskog C . The human protein atlas: A spatial map of the human proteome. Protein Sci. 2017; 27(1):233-244. PMC: 5734309. DOI: 10.1002/pro.3307. View

20.

Shannon P, Markiel A, Ozier O, Baliga N, Wang J, Ramage D . Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13(11):2498-504. PMC: 403769. DOI: 10.1101/gr.1239303. View