口腔鳞状细胞癌淋巴转移关键基因的筛选与鉴定

陈英; 罗丽; 钟雅静; 曾钦

doi:10.16016/j.1000-5404.201901143

您当前的位置：

首页 >

文章列表页 >

口腔鳞状细胞癌淋巴转移关键基因的筛选与鉴定

基础医学 | 更新时间：2026-01-09

- 口腔鳞状细胞癌淋巴转移关键基因的筛选与鉴定
- Screening and identification of key genes involved in lymphatic metastasis of oral squamous cell carcinoma
- 第三军医大学学报 2019年41卷第12期页码：1149-1155
- 作者机构：
  
  1.400014 重庆，重庆市人民医院口腔科
  2.400037 重庆，陆军军医大学(第三军医大学)第二附属医院口腔科
- 作者简介：
  
  [陈英，E-mail: chenying_cq@yeah.net CHEN Ying, E-mail: chenying_cq@yeah.net
- 基金信息：
- DOI：10.16016/j.1000-5404.201901143
  中图分类号： R318.04;R73-37;R739.85
- 收稿：2019-01-17，
  
  修回：2019-03-10，
  
  纸质出版：2019-06-30
- 稿件说明：
移动端阅览
陈英, 罗丽, 钟雅静, 等. 口腔鳞状细胞癌淋巴转移关键基因的筛选与鉴定[J]. 第三军医大学学报, 2019,41(12):1149-1155.

Ying CHEN, Li LUO, Yajing ZHONG, et al. Screening and identification of key genes involved in lymphatic metastasis of oral squamous cell carcinoma[J]. Journal of Third Military Medical University, 2019, 41(12): 1149-1155.
陈英, 罗丽, 钟雅静, 等. 口腔鳞状细胞癌淋巴转移关键基因的筛选与鉴定[J]. 第三军医大学学报, 2019,41(12):1149-1155. DOI： 10.16016/j.1000-5404.201901143.

Ying CHEN, Li LUO, Yajing ZHONG, et al. Screening and identification of key genes involved in lymphatic metastasis of oral squamous cell carcinoma[J]. Journal of Third Military Medical University, 2019, 41(12): 1149-1155. DOI： 10.16016/j.1000-5404.201901143.

摘要

目的

筛选口腔鳞状细胞癌(oral squamous cell carcinoma，OSCC)发生淋巴转移的关键基因，并对其进行生物信息学分析及鉴定。

方法

从基因表达数据库(gene expression omnibus，GEO)中下载OSCC表达谱芯片GSE2280，利用在线工具GEO2R对表达差异基因(differentially expressed genes，DEGs)进行筛选。基于DAVID数据库对DEGs进行GO分析及KEGG通路分析，运用STRING数据库及Cytoscape软件构建蛋白相互作用网络。使用CytoHubba插件鉴定枢纽基因，并使用肿瘤基因图谱数据库(the cancer genome atlas，TCGA)在口腔肿瘤病例中进行枢纽基因突变的生存分析比较。

结果

在OSCC发生淋巴转移与未发生淋巴转移的患者中共筛选出131个DEGs，其中74个上调基因，57个下调基因。上调基因GO功能主要富集在消化降解(GO:0007586)、中间丝细胞骨架(GO:0045111)、受损的DNA结合(GO:0003684)，主要参与胰腺分泌(hsa04972)和代谢途径(hsa01100)，下调基因GO功能富集在细胞外基质组成(GO:0030198)、胶原三聚体(GO:0005581)和细胞外基质结构成分(GO:0005201)，主要参与细胞外基质受体相互作用(hsa04512)及蛋白质消化吸收(hsa04974)。关键的枢纽基因包括：DHCR24、ALDH3A1、COL5A1、HSPG2、APOE、TP63、VCAN。枢纽基因分析结果显示：TP63突变的患者出现生存率降低的趋势(

=0.717)，VCAN突变的患者呈现生存率升高的趋势(

=0.568)，但生存率差异均无统计学意义。

结论

DHCR24、ALDH3A1、COL5A1、HSPG2、APOE、TP63、VCAN关键基因在OSCC淋巴转移中具有潜在的基础和临床研究价值。

Abstract

Objective

To screen the key genes associated with lymphatic metastasis of oral squamous cell carcinoma (OSCC) and analyze their roles and the impact of their mutations on the patients' survival through a bioinformatics approach.

Methods

The OSCC expression profile chip GSE2280 was downloaded from GEO database

and the differentially expressed genes (DEGs) were screened using the online tool GEO2R. Based on DAVID database

GO analysis and KEGG pathway analysis of the DEGs were carried out

and the protein interaction network was constructed using STRING database and Cytoscape software. CytoHubba Plug-in was used to identify the hub genes

and The Cancer Genome Atlas (TCGA) database was used to analyze the survival outcomes of oral cancer patients with mutations of these hub genes.

Results

We identified a total of 131 DEGs

including 74 up-regulated and 57 down-regulated genes

between OSCC patients with lymphatic metastasis and those without lymphatic metastasis. The up-regulated genes were enriched in digestion and degradation (GO:0007586)

intermediate filament cytoskeleton (GO:0045111)

and impaired DNA binding (GO:0003684)

and participated mainly in pancreatic secretion (hsa04972) and metabolic pathway (hsa01100). The down-regulated genes were enriched in extracellular matrix composition (GO:0030198)

collagen trimer (GO:0005581) and extracellular matrix structural components (GO:0005201)

and participated in extracellular matrix receptor interaction (hsa04512) and protein digestion and absorption (hsa04974). The key hub genes involved in lymphatic metastasis of OSCC included DHCR24

ALDH3A1

COL5A1

HSPG2

APOE

TP63 and VCAN. Analysis of the data from TCGA database showed that the survival rate of patients with TP63 mutation was significantly decreased (

=0.717)

and the patients with VCAN mutation appeared to have an increased survival rate

but this increase was not statistically significant (

=0.568).

Conclusion

DHCR24

ALDH3A1

COL5A1

HSPG2

APOE

TP63 and VCAN genes may have potential values in both preclinical and clinical studies of lymphatic metastasis of OSCC.

关键词

Keywords

references

WARNAKULASURIYA S. Living with oral cancer: epidemi-ology with particular reference to prevalence and life-style changes that influence survival[J]. Oral Oncol, 2010, 46(6): 407-410. DOI: 10.1016/j.oraloncology.2010.02.015.

SEVERINO P, OLIVEIRA L S, ANDREGHETTO F M, et al. Small RNAs in metastatic and non-metastatic oral squamous cell carcinoma[J]. BMC Med Genomics, 2015, 8: 31. DOI: 10.1186/s12920-015-0102-4.

LAIMER K, BLASSNIG N, SPIZZO G, et al. Prognostic significance of 14-3-3sigma expression in oral squamous cell carcinoma (OSCC)[J]. Oral Oncol, 2009, 45(2): 127-134. DOI: 10.1016/j.oraloncology.2008.04.006.

TORUNER G A, ULGER C,ALKAN M, et al. Association between gene expression profile and tumor invasion in oral squamous cell carcinoma[J]. Cancer Genet Cytogenet, 2004, 154(1): 27-35. DOI: 10.1016/j.cancergencyto.2004.01.026.

HSIA K T, LIU C J, MAR K, et al. Impact of apurinic/apyrimidinic endonuclease 1/redox factor-1 on treatment response and survival in oral squamous cell carcinoma[J]. Head Neck, 2016, 38(4): 550-559. DOI: 10.1002/hed.23927.

TATANGELO F, DI MAURO A, SCOGNAMIGLIO G, et al. Posterior HOX genes and HOTAIR expression in the proximal and distal colon cancer pathogenesis[J]. J Transl Med, 2018, 16(1): 350. DOI: 10.1186/s12967-018-1725-y.

BELACEL N, WANG Q, CUPERLOVIC-CULF M. Clustering methods for microarray gene expression data[J]. OMICS, 2006, 10(4): 507-531. DOI: 10.1089/omi.2006.10.507.

O'DONNELL R K, KUPFERMAN M, WEI S J, et al. Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity[J]. Oncogene, 2005, 24(7): 1244-1251. DOI: 10.1038/sj.onc.1208285.

SZKLARCZYK D, MORRIS J H, COOK H, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible[J]. Nucleic Acids Res, 2017, 45(D1): D362-D368. DOI: 10.1093/nar/gkw937.

KOHL M, WIESE S, WARSCHEID B. Cytoscape: software for visualization and analysis of biological networks[J]. Methods Mol Biol, 2011, 696: 291-303. DOI: 10.1007/978-1-60761-987-1_18.

CHIN C H, CHEN S H, WU H H, et al. CytoHubba: identifying hub objects and sub-networks from complex interactome[J]. BMC Syst Biol, 2014, 8(Suppl 4): S11. DOI: 10.1186/1752-0509-8-S4-S11.

LIU H, LI J J, YANG Y, et al. Alterations of 63 hub genes during lingual carcinogenesis in C57BL/6J mice[J]. Sci Rep, 2018, 8(1): 12626. DOI: 10.1038/s41598-018-31103-3.

PEDRO N F, BISELLI J M, MANIGLIA J V, et al. Candidate biomarkers for oral squamous cell carcinoma: differential expression of oxidative stress-related genes[J]. Asian Pac J Cancer Prev, 2018, 19(5): 1343-1349. DOI: 10.22034/APJCP.2018.19.5.1343.

DAI M, ZHU X L, LIU F, et al. Cholesterol synthetase DHCR24 induced by insulin aggravates cancer invasion and progesterone resistance in endometrial carcinoma[J]. Sci Rep, 2017, 7: 41404. DOI: 10.1038/srep41404.

YAN J, DE MELO J, CUTZ J C, et al. Aldehyde dehydrogenase 3A1 associates with prostate tumorigenesis[J]. Br J Cancer, 2014, 110(10): 2593-2603. DOI: 10.1038/bjc.2014.201.

LI G, LI X, YANG M, et al. Prediction of biomarkers of oral squamous cell carcinoma using microarray technology[J]. Sci Rep, 2017, 7: 42105. DOI: 10.1038/srep42105.

GRINDEL B J, MARTINEZ J R, TELLMAN T V, et al. Matrilysin/MMP-7 cleavage of Perlecan/HSPG2 complexed with semaphorin 3A supports FAK-mediated stromal invasion by prostate cancer cells[J]. Sci Rep, 2018, 8(1): 7262. DOI: 10.1038/s41598-018-25435-3.

GRINDEL B, LI Q L, ARNOLD R, et al. Correction: Perlecan/HSPG2 and matrilysin/MMP-7 as indices of tissue invasion: tissue localization and circulating perlecan fragments in a cohort of 288 radical prostatectomy patients[J]. Oncotarget, 2016, 7(37): 60775. DOI: 10.18632/oncotarget.11976.

JAYAKAR S K, LOUDIG O, BRANDWEIN-GENSLER M, et al. Apolipoprotein E promotes invasion in oral squamous cell carcinoma[J]. Am J Pathol, 2017, 187(10): 2259-2272. DOI: 10.1016/j.ajpath.2017.06.016.

ZHUANG Z, XIE N, HU J, et al. Interplay between ΔNp63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma[J]. Oncotarget, 2017, 8(13): 21954-21973. DOI: 10.18632/oncotarget.15752.

ABRAM T J, PICKERING C R, LANG A K, et al. Risk stratification of oral potentially malignant disorders in fanconi anemia patients using autofluorescence imaging and cytology-on-a chip assay[J]. Transl Oncol, 2018, 11(2): 477-486. DOI: 10.1016/j.tranon.2018.01.014.

ZHANG Y, ZOU X, QIAN W, et al. EnhancedPAPSS2/VCAN sulfation axis is essential for Snail-mediated breast cancer cell migration and metastasis[J]. Cell Death Differ, 2019, 26(3): 565-579. DOI: 10.1038/s41418-018-0147-y.

SALEM M, O'BRIEN J A, BERNAUDO S, et al. miR-590-3p promotes ovarian cancer growth and metastasis via a novel FOXA2-versican pathway[J ] . Cancer Res, 2018, 78(15): 4175-4190. DOI: 10.1158/0008-5472.CAN-17-3014.

LIU X G, HAN C Y, LIAO X W, et al. Genetic variants in the exon region of versican predict survival of patients with resected early-stage hepatitis B virus-associated hepatocellular carcinoma[J]. Cancer Manag Res, 2018, 10: 1027-1036. DOI: 10.2147/CMAR.S161906.

MITSUI Y, SHIINA H, KATO T, et al. Versican promotes tumor progression, metastasis and predicts poor prognosis in renal carcinoma[J]. Mol Cancer Res, 2017, 15(7): 884-895. DOI: 10.1158/1541-7786.MCR-16-0444.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

DLGAP5通过调控Warburg效应促进口腔鳞状细胞癌的进展

β-arrestin1在口腔鳞状细胞癌中的表达及其对细胞增殖、迁移、侵袭的作用

基于普通转录组和单细胞转录组测序解析间质型胃癌复发风险相关的肿瘤细胞及微环境特征

筛选影响结肠癌预后的焦亡相关lncRNA和基因

转录因子LMO3对子宫内膜癌患者预后的影响