基于生物信息学分析筛选舌鳞癌的关键基因

doi:10.19438/j.cjoms.2023.05.005

摘要/Abstract

摘要： 目的：利用生物信息学方法筛选舌癌的关键基因,探讨其与舌癌进展相关的潜在功能和通路机制。方法：分析微阵列数据集GSE13601,筛选出差异表达基因。利用注释、可视化和集成发现数据库（DAVID）进行基因本体论（GO）及京都基因和基因组百科全书（KEGG）通路分析。利用STRING数据库构建蛋白质相互作用网络、癌症基因组图谱数据库（TCGA）测序数据评估舌癌关键基因的表达。结果：共筛选出101个差异表达基因及20个关键基因,进一步研究发现,MYH2、MYLPF、NEB、ACTN2、DES、TMP2等关键基因影响舌癌患者的生存率,并且MYH2、MYLPF、ACTN2、DES、TPM2、TNNC1、MYL1、MYH7和TNNI2等基因的表达与舌癌的临床分期相关。结论：MYH2、MYLPF、NEB、ACTN2、DES、TMP2、MYL1、TNNC1、MYH7和TNNI2可能参与舌癌的发生、发展,具备成为舌癌潜在生物标志物和治疗靶点的潜力。

关键词: 舌鳞癌, 关键基因, 生物标志物, 生物信息分析

Abstract: PURPOSE: To screen hub genes for tongue squamous cell carcinoma(TSCC) by bioinformatic methods and explore their potential functional and pathway mechanisms associated with TSCC progression. METHODS: The microarray datasets GSE13601 was analysed to screen out the differentially expressed genes. The database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. STRING database was used to construct protein interaction networks, and the abnormal expression of key genes in TSCC was assessed by sequencing data from The Cancer Genome Atlas (TCGA) database. RESULTS: A total of 101 differentially expressed genes and 20 key genes were screened, and further studies revealed that key genes such as MYH2, MYLPF, NEB, ACTN2, DES and TMP2 affected the survival rate of TSCC patients, and the expression of MYH2, MYLPF, ACTN2, DES, TPM2, TNNC1, MYL1, MYH7 and TNNI2 correlated with the clinical stage of TSCC. CONCLUSIONS: MYH2, MYLPF, NEB, ACTN2, DES, TMP2, TNNC1, TPM2, MYH7 and TNNI2 may participate in the development of TSCC and have the potential to become biomarkers and therapeutic targets for TSCC.

Key words: Tongue squamous cell carcinoma, Hub genes, Biomarkers, Bioinformatic analysis

中图分类号:

R739.8

曾慧, 江花香, 胡彦昌, 杨丰瑞, 王军. 基于生物信息学分析筛选舌鳞癌的关键基因[J]. 中国口腔颌面外科杂志, 2023, 21(5): 452-460.

ZENG Hui, JIANG Hua-xiang, HU Yan-chang, YANG Feng-rui, WANG Jun. Screening of hub genes in tongue squamous cell carcinoma based on bioinformatics analysis[J]. China J Oral Maxillofac Surg, 2023, 21(5): 452-460.

参考文献

[1] Zhang H, Liu J, Fu X, et al.Identification of key genes and pathways in tongue squamous cell carcinoma using bioinformatics analysis[J]. Med Sci Monit, 2017, 23: 5924-5932.
[2] Zhang Q, Li L, Lai Y, et al. Silencing of SPP1 suppresses progression of tongue cancer by mediating the PI3K/Akt signaling pathway[J]. Technol Cancer Res Treat, 2020, 19: 153303382097 1306.
[3] Wang R, Zhou X, Wang H, et al.Integrative analysis of gene expression profiles reveals distinct molecular characteristics in oral tongue squamous cell carcinoma[J]. Oncol Lett, 2019, 17(2): 2377-2387.
[4] Zhong P, Liu L, Shen A, et al.Five extracellular matrix-associated genes upregulated in oral tongue squamous cell carcinoma: an integrated bioinformatics analysis[J]. Oncol Lett, 2019, 18(6): 5959-5967.
[5] Xie N, Wang C, Liu X, et al.Tumor budding correlates with occult cervical lymph node metastasis and poor prognosis in clinical early-stage tongue squamous cell carcinoma[J]. J Oral Pathol Med, 2015, 44(4): 266-272.
[6] Hayashi Y, Minamiyama S, Ohya T, et al.Daily cisplatin and weekly docetaxel versus weekly cisplatin intra-arterial chemoradiotherapy for late T2-3 tongue cancer: a pilot and feasibility trial[J]. Medicina (Kaunas), 2018, 54(4):52-61.
[7] Sahingur SE, Yeudall WA.Chemokine function in periodontal disease and oral cavity cancer[J]. Front Immunol, 2015, 6: 214-228.
[8] Hu H, Wang Y, Li Z, et al.Overexpression of suppressor of zest 12 is associated with cervical node metastasis and unfavorable prognosis in tongue squamous cell carcinoma[J]. Cancer Cell Int, 2017, 17: 26-32.
[9] Gallo O, Masini E, Bianchi B, et al.Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma[J]. Hum Pathol, 2002, 33(7): 708-714.
[10] Lao XM, Liang YJ, Su YX, et al.Distribution and significance of interstitial fibrosis and stroma-infiltrating B cells in tongue squamous cell carcinoma[J]. Oncol Lett, 2016, 11(3): 2027-2034.
[11] Borchers A, Pieler T.Programming pluripotent precursor cells derived from Xenopus embryos to generate specific tissues and organs[J]. Genes (Basel), 2010, 1(3): 413-426.
[12] Gerhard DS, Wagner L, Feingold EA, et al.The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)[J]. Genome Res, 2004, 14(10B): 2121-2127.
[13] Gurnett CA, Alaee F, Desruisseau D, et al.Skeletal muscle contractile gene (TNNT3, MYH3, TPM2) mutations not found in vertical talus or clubfoot[J]. Clin Orthop Relat Res, 2009, 467(5): 1195-1200.
[14] Tiso N, Majetti M, Stanchi F, et al.Fine mapping and genomic structure of ACTN2, the human gene coding for the sarcomeric isoform of alpha-actinin-2, expressed in skeletal and cardiac muscle[J]. Biochem Biophys Res Commun, 1999, 265(1): 256-259.
[15] Zammit PS, Cohen A, Buckingham ME, et al.Integration of embryonic and fetal skeletal myogenic programs at the myosin light chain 1f/3f locus[J]. Dev Biol, 2008, 313(1): 420-433.
[16] Zhang SZ, Xie HQ, Xu Y, et al.Regulation of cell proliferation by fast Myosin light chain 1 in myoblasts derived from extraocular muscle, diaphragm and gastrocnemius[J]. Exp Biol Med (Maywood), 2008, 233(11): 1374-1384.
[17] Cui C, Yin H, Han S, et al.Quantitative proteomic and phosphoproteomic analysis of chicken skeletal muscle during embryonic development[J]. Anim Biotechnol, 2023, 34(2): 122-133.
[18] Nakagawa H, Suzuki H, Machida S, et al.Contribution of the LIM domain and nebulin-repeats to the interaction of Lasp-2 with actin filaments and focal adhesions[J]. PLoS One, 2009, 4(10): e7530.
[19] Yang K, Zhang S, Zhang D, et al.Identification of SERPINE1, PLAU and ACTA1 as biomarkers of head and neck squamous cell carcinoma based on integrated bioinformatics analysis[J]. Int J Clin Oncol, 2019, 24(9): 1030-1041.
[20] Bermúdez-jiménez FJ, Carriel V, Brodehl A, et al. Novel desmin mutation p.Glu401Asp impairs filament formation, disrupts cell membrane integrity, and causes severe arrhythmogenic left ventricular cardiomyopathy/dysplasia[J]. Circulation, 2018, 137(15): 1595-1610.
[21] Landstrom AP, Parvatiyar MS, Pinto JR, et al.Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1-encoded troponin C[J]. J Mol Cell Cardiol, 2008, 45(2): 281-288.
[22] Schreckenbach T, Schröder JM, Voit T, et al.Novel TPM3 mutation in a family with cap myopathy and review of the literature[J]. Neuromuscul Disord, 2014, 24(2): 117-124.
[23] Toydemir RM, Bamshad MJ.Sheldon-hall syndrome[J]. Orphanet J Rare Dis, 2009, 4(1): 11-15.
[24] Savarese M, Maggi L, Vihola A, et al.Interpreting genetic variants in titin in patients with muscle disorders[J]. JAMA Neurol, 2018, 75(5): 557-565.
[25] Alhopuro P, Karhu A, Winqvist R, et al.Somatic mutation analysis of MYH11 in breast and prostate cancer[J]. BMC Cancer, 2008, 8: 263-267.
[26] Fokstuen S, Lyle R, Munoz A, et al.A DNA resequencing array for pathogenic mutation detection in hypertrophic cardiomyopathy[J]. Hum Mutat, 2008, 29(6): 879-885.
[27] Tian T, Wang J, Wang H, et al.A low prevalence of sarcomeric gene variants in a Chinese cohort with left ventricular non-compaction[J]. Heart Vessels, 2015, 30(2): 258-264.
[28] Chen Z, Zhao TJ, Li J, et al.Slow skeletal muscle myosin-binding protein-C(MyBPC1) mediates recruitment of muscle-type creatine kinase(CK) to myosin[J]. Biochem J, 2011, 436(2): 437-445.
[29] Wu W, Ren Z, Zhang L, et al.Overexpression of Six1 gene suppresses proliferation and enhances expression of fast-type muscle genes in C2C12 myoblasts[J]. Mol Cell Biochem, 2013, 380(1-2): 23-32.
[30] Buvoli M, Hamady M, Leinwand LA, et al.Bioinformatics assessment of beta-myosin mutations reveals myosin's high sensitivity to mutations[J]. Trends Cardiovasc Med, 2008, 18(4): 141-149.
[31] Li Y, Chen Y, Li J, et al.Molecular characterization, expression profile and polymorphisms of the porcine TNNC2 gene[J]. Hereditas, 2008, 145(6): 274-282.
[32] Calame DG, Fatih J, Herman I, et al.Biallelic pathogenic variants in TNNT3 associated with congenital myopathy[J]. Neurol Genet, 2021, 7(3): e589.
[33] Vesty A, Gear K, Biswas K, et al.Oral microbial influences on oral mucositis during radiotherapy treatment of head and neck cancer[J]. Support Care Cancer, 2020, 28(6): 2683-2691.
[34] Vered M, Shnaiderman-shapiro A, Zlotogorski-hurvitz A, et al. Cancer-associated fibroblasts in the tumor microenvironment of tongue carcinoma is a heterogeneous cell population[J]. Acta Histochem, 2019, 121(8): 151446.
[35] Batta N, Pandey M.Mutational spectrum of tobacco associated oral squamous carcinoma and its therapeutic significance[J]. World J Surg Oncol, 2019, 17(1): 198-210.
[36] Agarwal M, Sharma A, Kumar P, et al. Myosin heavy chain-embryonic regulates skeletal muscle differentiation during mammalian development[J]. Development, 2020, 147(7): dev184507.
[37] Martin AF, Bhatti S, Paul RJ.C-terminal isoforms of the myosin heavy chain and smooth muscle function[J]. Comp Biochem Physiol B Biochem Mol Biol, 1997, 117(1): 3-11.
[38] Chen Z, Li XY, Guo P, et al.MYBPC2 and MYL1 as significant gene markers for rhabdomyosarcoma[J]. Technol Cancer Res Treat, 2021, 20: 1533033820979669.
[39] Chong JX, Talbot JC, Teets EM, et al.Mutations in MYLPF cause a novel segmental amyoplasia that manifests as distal arthrogryposis[J]. Am J Hum Genet, 2020, 107(2): 293-310.
[40] Lee HY, Kim J, Park SJ.Role of α-actinin 2 in cytoadherence and cytotoxicity of Trichomonas vaginalis[J]. J Microbiol Biotechnol, 2017, 27(10): 1844-1854.
[41] O'sullivan LR, Cahill MR, Young PW. The importance of alpha-actinin proteins in platelet formation and function, and their causative role in congenital macrothrombocytopenia[J]. Int J Mol Sci, 2021, 22(17): 9363.
[42] Ranta-aho J, Olive M, Vandroux M, et al. Mutation update for the ACTN2 gene[J]. Hum Mutat, 2022, 43(12): 1745-1756.
[43] Zech ATL, Prondzynski M, Singh SR, et al.ACTN2 mutant causes proteopathy in human iPSC-derived cardiomyocytes[J]. Cells, 2022, 11(17): 2745-2761.
[44] Meng LB, Shan MJ, Qiu Y, et al.TPM2 as a potential predictive biomarker for atherosclerosis[J]. Aging (Albany NY), 2019, 11(17): 6960-6982.