BIRC5在三阴乳腺癌中的表达及其临床意义-东南大学学报医学版

BIRC5在三阴乳腺癌中的表达及其临床意义

单位：1. 海南医学院研究生院, 海南海口 571199;
2. 海南医学院第二附属医院放疗科, 海南海口 570311;
3. 海南医学院第二附属医院甲乳外科, 海南海口 570311

分类号：R737.9

出版年·卷·期（页码）：2022·41·第二期（241-245）

摘要：

目的:寻找预后不良的三阴乳腺癌(TNBC)潜在的预后分子标志物。方法:从GEO数据库下载GSE76275的基因表达谱。该微阵列由67个非TNBC和198个TNBC共265个样本组成。综合分析所有P＜0.05和倍数变化≥1或≤-1的差异表达基因(DEG)。结果:鉴定出138个上调基因和210个下调基因,并进行基因本体论(GO)、京都基因与基因组途径百科全书(KEGG)富集分析。这些基因主要参与细胞增殖、蛋白水解、蛋白质同源二聚化活性、钙离子结合、序列特异性DNA结合、细胞周期和PPAR信号通路的生物学过程。利用蛋白质相互作用网络鉴定了10个中枢基因,利用GEPIA进一步进行生存分析,筛选出BIRC5为TNBC的预后关键基因。结论:鉴定出的这些途径和基因可以帮助理解TNBC的发展机制;BIRC5可能是TNBC治疗的潜在靶点。

Objective: To find potential molecular prognostic markers for triple-negative breast cancer(TNBC) with poor prognosis. Methods: The gene expression profile of GSE76275 from GEO database was downloaded. The microarray consisted of 265 samples, including 67 non-TNBC and 198 TNBC. Comprehensive analysis of all differentially expressed genes(DEG) with P＜0.05 and fold change ≥1 or ≤-1 was performed. Results: One hundred and thirty-eight up-regulated genes and 210 down-regulated genes were identified, and gene ontology(GO) and Kyoto Encyclopedia of Genes and Genome Pathways(KEGG) enrichment analysis were performed. These genes were mainly involved in the biological processes of cell proliferation, proteolysis, protein homodimerization activity, calcium ion binding, sequence-specific DNA binding, cell cycle and PPAR signaling pathway. The protein interaction network was used to identify 10 central genes, and GEPIA was used for further survival analysis. BIRC5 was screened out as a key prognostic gene for TNBC. Conclusion: The identified pathways and genes can help understand the development mechanism of TNBC. BIRC5 may be a potential target for TNBC treatment.

参考文献：

[1] HUO X F,SHEN G S,LIU Z,et al.Addition of immunotherapy to chemotherapy for metastatic triple-negative breast cancer:a systematic review and meta-analysis of randomized clinical trials[J].Crit Rev Oncol Hematol,2021,168(11):103530.
[2] LEHMANN B D,BAUER J A,CHEN X,et al.Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies[J].J Clin Invest,2011,121(7):2750-2767.
[3] MEI-YIN C P,POLLEY A L F,SAMUEI L,et al.A clinical calculator to predict disease outcomes in women with triple-negative breast cancer[J].Breast Cancer Res Treat,2021,185(3):557-566.
[4] BURSTEIN M D,TSIMELZON A,POAGE G M,et al.Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer[J].Clin Cancer Res,2015,21(7):1688-1698.
[5] LUND M J,TRIVERS K F,PORTER P L,et al.Race and triple negative threats to breast cancer survival:a population-based study in Atlanta,GA[J].Breast Cancer Res Treat,2009,113(2):357-370.
[6] BAUER K R,BROWN M,CRESS R D,et al.Descriptive analysis of estrogen receptor(ER)-negative,progesterone receptor(PR)-negative,and HER2-negative invasive breast cancer,the so-called triple-negative phenotype:a population-based study from the California cancer Registry[J].Cancer,2007,109(9):1721-1728.
[7] WEI L Z,YANG W D,QIN Y,et al.6-Gingerol stabilized the p-VEGFR2/ VE-cadherin/beta-catenin/actin complex promotes microvessel normalization and suppresses tumor progression[J].J Exp Clin Cancer Res,2019,38(1):285.
[8] HAMMOND M E,HAYES D F,DOWSETT M,et al.American society of clinical oncology/college of American pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer[J].J Oncol Pract,2010,28(16):2784-2795.
[9] REIS-FILHO J S,TUTT A N J.Triple negative tumours:a critical review[J].Histopathology,2008,52(1):108-118.
[10] GONZALEZ-ANGULO A M,TIMMS K M,LIU S,et al.Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer[J].Clin Cancer Res,2011,17(5):1082-1089.
[11] GODOY-ORTIZ A,SANCHEZ-MUNOZ A,CHICA-PARRADO M R,et al.Deciphering HER2 breast cancer disease:biological and clinical implications[J].Front Oncol,2019,9(10):1124.
[12] VOUTILAINEN S,HEIKKILA P,SAMPO M,et al.Expression of markers of stem cell characteristics,epithelial-mesenchymal transition,basal-like phenotype,proliferation,and androgen receptor in metaplastic breast cancer and their prognostic impact[J].Acta Oncologica,2021,60(9):1233-1239.
[13] SONG J Y,LI X P,QIN X J,et al.A fourteen-lncRNA risk score system for prognostic prediction of patients with non-small cell lung cancer[J].Cancer Biomarkers,2020,29(4):493-508.
[14] YUAN Q Q,ZHENG L W,LIAO Y Q,et al.Overexpression of CCNE1 confers a poorer prognosis in triple-negative breast cancer identified by bioinformatic analysis[J].World J Surg Oncol,2021,19(1):86.
[15] XI X,CHU Y,LIU N,et al.Joint bioinformatics analysis of underlying potential functions of hsa-let-7b-5p and core genes in human glioma[J].J Transl Med,2019,17(1):129.
[16] CASCIANO J C,PERRY C,COHEN-NOWAK A J,et al.MYC regulates fatty acid metabolism through a multigenic program in claudin-low triple negative breast cancer[J].Br J Cancer,2020,122(6):868-884.
[17] XIAO T,ZHONG W,ZHAO J,et al.Polyphyllin Ⅰ suppresses the formation of vasculogenic mimicry via Twist1/VE-cadherin pathway[J].Cell Death Dis,2018,9(9):906.
[18] DENG J L,XU Y H,WANG G.Identification of potential crucial genes and key pathways in breast cancer using bioinformatic analysis[J].Front Genet,2019,10(8):695.
[19] ZHONG W L,SUN B,GAO W Q,et al.Salvianolic acid a targeting the transgelin-actin complex to enhance vasoconstriction[J].EBio Medicine,2018,37(11):246-258.
[20] SADOVSKA L,EGLITIS J,LINE A.Extracellular vesicles as biomarkers and therapeutic targets in breast cancer[J].Anticancer Res,2015,35(12):6379-6390.
[21] WANG Y,ZHANG T,KWIATKOWSKI N,et al.CDK7-dependent transcriptional addiction in triple-negative breast cancer[J].Cell,2015,163(1):174-186.
[22] LI F Z,AlJAHDALI I,LING X.Cancer therapeutics using survivin BIRC5 as a target:what can we do after over two decades of study[J].J Exp Clin Cancer Res,2019,38(1):368.
[23] WHEATLEY S P,ALTIERI D C.Survivin at a glance[J].J Cell Sci,2019,132(7):jcs22382.
[24] LI F Z.Discovery of survivin inhibitors and beyond[J].Int Rev Cell Mol Biol,2013,305:217-252.
[25] SUZUKI S,YANAMOTO M,SANOMACHI T,et al.Brexpiprazole,a serotonin-dopamine activity modulator,can sensitize glioma stem cells to osimertinib,a third-generation EGFR-TKI,via survivin reduction[J].Cancers,2019,11(7):947.
[26] PLESCIA J,SALZ W,XIA F.Rational design of shepherdin,a novel anticancer agent[J].Cancer Cell,2005,7(5):457-468.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录