Journal of Prevention and Treatment for Stomatological Diseases ›› 2021, Vol. 29 ›› Issue (1): 27-33.doi: 10.12016/j.issn.2096-1456.2021.01.004

• Basic Study • Previous Articles     Next Articles

Identification of potential genetic markers in prognosis of oral squamous cell carcinoma patients by bioinformatic analysis

WANG Liye1(),GAO Ying1,2(),TIAN Chun2   

  1. 1. Shanxi Medical University Hospital of Stomatology, Taiyuan 030001, China
    2. Department of Stomatology, First Hospital of Shanxi Medical University, Taiyuan 030001, China
  • Received:2020-03-03 Revised:2020-05-11 Online:2021-01-20 Published:2020-11-18
  • Contact: Ying GAO E-mail:773565363@qq.com;flygaoying1999@163.com
  • Supported by:
    Natural Science Foundation of Shanxi Province(201801D121343)

Abstract:

Objective To analyze the differentially expressed genes of patients with oral squamous cell carcinoma (OSCC) from paracarcinoma through biological information analysis to preliminarily identify OSCC-associated genes. Methods GSE23558, GSE37991 and GSE30784 were downloaded from the Gene Expression Omnibus (GEO), which is the mRNA expression profile dataset. The differentially expressed genes (DEGs) were identified based on the gene ontology and the Kyoto Encyclopedia of Genes and Genomes. Then, the protein-protein interaction (PPI) network was constructed using the STRING online tool, and Cytoscape was used to filter the critical genes. Furthermore, key genes involved in the survival of patients with OSCC were analyzed using Kaplan-Meier analysis. The expression of hub genes was validated based on GEPIA(http://gepia.cancer-pku.cn/). Results A total of 212 DEGs were screened, and further analysis revealed 16 core genes, among which the core genes associated with prognosis included aurora kinase A (AURKA), aurora kinase B (AURKB), apoptosis inhibiting factor 5 (BIRC5), cell division cycle 6 (CDC6), E2F transcription factor 7 (E2F7), ubiquitin-like with PHD and ring finger domains 1 (UHRF1). These key genes were highly expressed in patients with oral squamous cell carcinoma, and the survival time of patients was short; the difference was statistically significant (P < 0.05). Conclusion AURKA, AURKB, BIRC5, CDC6, E2F7 and UHRF1 may be useful as potential biomarkers for OSCC prognosis prediction.

Key words: oral squamous cell carcinoma, bioinformatics, biomarker, differentially expressed genes, microarray, aurora kinase, baculoviral IAP repeat containing 5, cell division cycle 6, E2F transcription factor 7, ubiquitin-like with PHD and ring finger domains 1

CLC Number: 

  • R78

Table 1

Venn diagrams of differentially expressed genes of OSCC"

DEGs Genes Name
Up-regulated ADAM12 HOXA1 LY6K ITGA3 BIRC5 FOXM1 PCDH7 DENND1A IL24 CDC6 AURKA SH2D2A AURKB SPP1 MELK TMEM132A GTSE1 E2F7 LAMA3 NAA40 MMP1 CD109 BNC1 CDH3 MMP3 LPAR3 CD276 AGRN CYP27B1 GALNT6 DCBLD1 PDE7A ARPC1B MCM2 COL4A6 CXCL10 LAMC2 GBP5 KIAA0101 MMP10 PLAU SLC28A3 HOMER3 ITGB4 FBLIM1 PTHLH TENM2 DSG2 CXCL11 SERINC2 PTK7 SPHK1 TNFRSF12A OASL TRIP13 TLDC1 HMGA2 ISG15 PDPN TK1 SHCBP1 DPP3 SERPINH1 PLEK2 INHBA CDCA3 CXCL9 CXCL5 KIF20A AIM2 UHRF1 SCG5 PPP4R4 WDR66
Down-regulated MITF DKK2 HNMT GDF10 BDH2 MYO5C KRT222 HLF TLE2 LONRF2 PBX1 VIT SYTL4 IL17D OMD PDGFD BEX2 ARHGEF26 DCT C1orf115 SH3BGRL2 C1QTNF7 NEGR1 RBP7 CAND2 NRXN1 PHYH GPD1L HRASLS CTTNBP2 ANGPTL1 ARHGAP20 NR3C2 SLC27A6 IL17RD OGN GIPC2 TCEAL2 NTRK2 PLCB4 NBEA MIR99AHG APOD F10 PID1 ZNF415 SUSD4 SCN7A PEG3 MYZAP TGFBR3 RORC BOC PGM5 FXYD1 GSTM5 PRELP CKMT2 PLP1 C2orf40 AOX1 GULP1 CFD RNASE4 CYP4B1 PTN ZSCAN18 CHRDL1 CILP SYNPO2 FAM150B RERG SLC16A7 SOD3 CRYAB TSPAN8 CD36 DCLK1 COL21A1 SLC47A1 TM7SF2 FAM149A ABCA8 HSPB2 ASPA MAN1C1 TNMD AMPD1 MYH11 GAMT ABI3BP C8orf22 ANG HPGD NTRK3 BEX4 TMEM100 PLIN1 CNTN3 DPT SORCS1 MFAP4 MGLL SCARA5 MAOB ATP1A2 ACADSB IGSF10 ACKR1 SORBS1 FGF7 LIFR STXBP6 PMP2 LGI1 2-Mar PPM1L PDZRN4 COX7A1 FAM189A2 FMO2 LMO3 ARHGAP6 FAM221A MYRIP CAB39L FAM107A CCDC85A PPP1R3C RRAGD TCEA3 MMRN1 GKAP1 GGTA1P MAMDC2 AR GATM SELENBP1

Figure 1

Gene ontology enrichment analysis results of differentially expressed genes in OSCC Red represents biological processes(BP), green represents cellular components(CC), and blue represents molecular function (MF); OSCC: oral squamous cell carcinoma; GO: gene ontology"

Figure 2

Differentially expressed genes in OSCC are involved in metabolic pathways The X-axis represents the ratio of gene number, and the Y-axis represents each signalling pathway; OSCC: oral squamous cell carcinoma"

Figure 3

Constructed protein-protein interaction network of differentially expressed genes in OSCC Module analysis was performed via Cytoscape software. Finally, 16 core genes were obtained: blue represents downregulated DEGs and red represents upregulated DEGs; OSCC: oral squamous cell carcinoma; MELK: maternal embryonic leucine zipper kinase; GTSE1: G2 and S phase-expressed protein 1; TK1: thymidine kinase 1; KIF20A: kinesin family member 20A; SHCBP1: SHCSH2-binding protein 1; MCM2: minichromosome maintenance protein 2; CDCA3: cell division cycle A3; TRIP13: thyroid hormone receptor interactor 13; FOXM1: Forkhead box protein M1; AURKA: aurora kinase A; AURKB: aurora kinase B; BIRC5: baculoviral IAP repeat containing 5; CDC6: cell division cycle 6; E2F7: E2F transcription factor 7; UHRF1: ubiquitin-like with PHD and ring finger domains 1"

Figure 4

The prognostic information of the core genes in OSCC The core genes had a significantly worse survival rate (P < 0.05); AURKA: aurora kinase A; AURKB: aurora kinase B; CDC6: cell division cycle 6; BIRC5: baculoviral IAP repeat containing 5; E2F7: E2F transcription factor 7; UHRF1: ubiquitin-like with PHD and ring finger domains 1; OSCC: oral squamous cell carcinoma"

Figure 5

Validation of the expression levels of critical genes in OSCC Six genes related to poor prognosis were analyzed using the GEPIA website; six genes had significant expression levels in OSCC specimens compared to normal specimens (*P < 0.05); red represents tumor tissues, and gray represents normal tissues; AURKA: aurora kinase A; AURKB: aurora kinase B; CDC6: cell division cycle 6;BIRC5: baculoviral IAP repeat containing 5; E2F7: E2F transcription factor 7; UHRF1: ubiquitin-like with PHD and ring finger domains 1; OSCC: oral squamous cell carcinoma"

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