微小染色体蛋白家族和染色体结构维持蛋白4基因在宫颈鳞状细胞癌组织中的表达及其生物信息学分析

doi:10.13481/j.1671-587X.20210224

Abstract

Abstract: Objective

To explore the prognostic factors of cervical squamous cell carcinoma by bioinformatics methods based on The Cancer Genome Atlas （TCGA） and Gene Expression Omnibus （GEO） databases.

Methods

The data of cervical squamous cell carcinoma were downloaded from TCGA and GEO databases. Perl and R software were used to screen the differential expression genes （DEGs） in normal and tumor tissues shared by the two databases. Gene Ontology （GO） function enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed to predict the mechanism of DEGs. Further， STRING database and Cytoscape software were used to construct a protein- protein interact （PPI） network， and screen the hub gene， and the survival analysis was performed combined with the clinical data.

Results

There were 226 DEGs including 170 up-regulation genes and 56 down-regulation genes in two databases. The GO enrichment analysis results showed that DEGs were mainly related to cell nuclear division， organelle division， mitosis and DNase activity. The KEGG pathway analysis results showed that the main enrichment was in the cell cycle， DNA replication， and p53 signaling pathway， etc. The survival analysis results showed that the minichromosome maintenance proteins （MCMs） genes， including MCM2， MCM5 and MCM6， and structural maintenance of chromosome 4 （SMC4） gene were all highly expressed in tumor tissue and significantly related to the prognosis of cervical squamous cell carcinoma （P<0.05）. Additionally， the up-regulated genes MCM2， MCM5 and MCM6 prolonged the survival time of the patients with cervical squamous cell carcinoma，and they were tumor suppressor genes； while SMC4 shortened the survival time of the patients with cervical squamous cell carcinoma，and they were carcinogenic genes.

Conclusion

As tumor suppressors genes， MCM2， MCM5 and MCM6 genes can inhibit the tumor development； as an oncogene， SMC4 gene can promote the progression of cervical squamous cell carcinoma.

Key words: cervical squamous cell carcinoma, TCGA database, GEO database, bioinformatics analysis

CLC Number:

R737.33

Yao LIN,Chunlin LIN,Qin WANG,Bin ZHANG,Shaoyu WANG,Guangwei ZHU. Expressions of minichromosome maintenance proteins and structural maintenance of chromosomes 4 genes in cervical squamous cell carcinoma tissue and bioinformation analysis[J].Journal of Jilin University(Medicine Edition), 2021, 47(2): 430-437.

Figures/Tables 6

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References 30

1	TORRE L A， BRAY F， SIEGEL R L， et al. Global cancer statistics， 2012 ［J］. CA Cancer J Clin， 2015， 65 （2）：87-108.
2	JEMAL A， BRAY F， CENTER M M， et al.Global cancer statistics ［J］. CA Cancer J Clin， 2011， 61（2）：69-90.
3	方丹妹.鳞癌抗原检测在宫颈癌及癌前病变诊断的价值［J］. 中国卫生标准管理， 2020， 11 （11）：35-37.
4	宋适寅.宫颈鳞状上皮肿瘤的病理诊断价值分析［J］. 当代医学， 2020， 26 （17）：173-174.
5	TOMCZAK K， CZERWINSKA P，WIZNEROWICZ M.The Cancer Genome Atlas （TCGA）：an immeasurable source of knowledge ［J］. Contemp Oncol Poznan Pol， 2015， 19 （1A）：A68-A77.
6	BARRETT T， WILHITE S E， LEDOUX P， et al. NCBI GEO： archive for functional genomics data sets--update ［J］. Nucleic Acids Res， 2013， 41 （Database issue）：D991-995.
7	CRISTESCU R， LEE J， NEBOZHY M， et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes ［J］. Nat Med， 2015， 21 （5）：449-456.
8	KIM E， JUNG S， PARK W S， et al.Upregulation of SLC2A3 gene and prognosis in colorectal carcinoma： analysis of TCGA data ［J］.BMC Cancer，2019，19（1）：1-10.
9	KIM I， CHOI S， KIM S. BRCA-Pathway： a structural integration and visualization system of TCGA breast cancer data on KEGG pathways ［J］. BMC Bioinformatics， 2018， 19 （）：42.
10	LIU X， WANG J， CHEN M， et al.Combining data from TCGA and GEO databases and reverse transcription quantitative PCR validation to identify gene prognostic markers in lung cancer ［J］. Oncol Targets Ther， 2019， 12：709-720.
11	张军.7 900例35~64岁农村妇女宫颈癌检查结果分析［J］. 卫生职业教育， 2019， 37 （23）：136-138.
12	乔友林，赵宇倩.宫颈癌的流行病学现状和预防［J］.中华妇幼临床医学杂志（电子版）， 2015， 11 （2）：1-6.
13	曹欢，刘冰，王晓丹. 宫颈病变流行病学分析及宫颈冷冻治疗新进展［J］. 分子诊断与治疗杂志， 2020， 12 （8）：1129-1132.
14	DONG J， WANG Q， LI L，et al. Upregulation of long non-coding RNA small nucleolar RNA host gene 12 contributes to cell growth and invasion in cervical cancer by acting as a sponge for MiR-424-5p ［J］. Cell Physiol Biochem， 2018， 45 （5）：2086-2094.
15	LIU X F， LI X Y， ZHENG P S，et al.DAX1 promotes cervical cancer cell growth and tumorigenicity through activation of Wnt/beta-catenin pathway via GSK3beta ［J］. Cell Death Dis， 2018， 9 （3）：339.
16	NAHAND J S， TAGHIZADEH-BOROUJENI S， KARIMZADEH M， et al.microRNAs： New prognostic， diagnostic， and therapeutic biomarkers in cervical cancer ［J］. J Cell Physiol， 2019， 234 （10）：17064-17099.
17	DAS M， SINGH S， PRADHAN S， et al.MCM paradox： abundance of eukaryotic replicative helicases and genomic integrity ［J］. Mol Biol Int， 2014， 2014：574850.
18	FOWLER C G，CHIASSON K B， LESLIE T H，et al.Auditory function in rhesus monkeys： effects of aging and caloric restriction in the Wisconsin monkeys five years later ［J］. Hear Res， 2010， 261 （1/2）：75-81.
19	CHEUNG C H Y， HSU C L， CHEN K P， et al. MCM2-regulated functional networks in lung cancer by multi-dimensional proteomic approach ［J］. Sci Rep， 2017， 7 （1）：13302.
20	ISSAC M S M， YOUSEF E， TAHIR M R， et al. MCM2， MCM4， and MCM6 in breast cancer： Clinical utility in diagnosis and prognosis ［J］.Neoplasia， 2019， 21 （10）：1015-1035.
21	REN B， YU G， TSENG G C， et al. MCM7 amplification and overexpression are associated with prostate cancer progression ［J］.Oncogene，2006，25 （7）：1090-1098.
22	YANG J， XIE Q， ZHOU H， et al.Proteomic analysis and NIR-II imaging of MCM2 protein in hepatocellular carcinoma ［J］. J Proteome Res， 2018， 17 （7）：2428-2439.
23	DEWAR J M， WALTER J C. Mechanisms of DNA replication termination ［J］. Nat Rev Mol Cell Biol， 2017， 18 （8）：507-516.
24	GIAGINIS C， GIAGINI A，TSOUROUFLIS G，et al.MCM-2 and MCM-5 expression in gastric adenocarcinoma： clinical significance and comparison with Ki-67 proliferative marker ［J］. Dig Dis Sci， 2011， 56 （3）：777-785.
25	CHEN Q Y， LIU L C， WANG J B，et al.CDK5RAP3 inhibits the translocation of MCM6 to influence the prognosis in gastric cancer［J］.J Cancer，2019，10 （19）：4488-4498.
26	ABE S， KURATA M， SUZUKI S， et al. Minichromosome maintenance 2 bound with retroviral Gp70 is localized to cytoplasm and enhances DNA-damage-induced apoptosis ［J］. PLoS One， 2012， 7 （6）：e40129.
27	高峻，杨宏新.微小染色体维持蛋白在肿瘤研究中的进展［J］. 包头医学院学报， 2014， 30 （1）：137-139.
28	DENG M， SUN J， XIE S，et al.Inhibition of MCM2 enhances the sensitivity of ovarian cancer cell to carboplatin ［J］. Mol Med Rep， 2019， 20（3）：2258-2266.
29	ZHANG C， KUANG M， LI M， et al. SMC4， which is essentially involved in lung development， is associated with lung adenocarcinoma progression ［J］. Sci Rep， 2016， 6：34508.
30	ZHOU B， YUAN T， LIU MG， et al.Overexpression of the structural maintenance of chromosome 4 protein is associated with tumor de-differentiation， advanced stage and vascular invasion of primary liver cancer ［J］. Oncol Rep， 2012， 28 （4）：1263-1268.

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Expressions of minichromosome maintenance proteins and structural maintenance of chromosomes 4 genes in cervical squamous cell carcinoma tissue and bioinformation analysis

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