DLL1基因在乳腺癌及三阴性乳腺癌中的表达及其临床意义
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摘要
目的研究DLL1基因在乳腺癌及三阴性乳腺癌中的表达情况,并探讨其表达差异与临床资料及预后的关系。方法从肿瘤基因组图谱(TCGA)数据库收集乳腺癌数据集,下载DLL1基因表达谱资料,取中位数分为高表达组与低表达组,分析其与临床资料及病例特征的关系;利用Kaplan-Meier Plotter分析DLL1与乳腺癌患者预后的相关性。结果 DLL1在乳腺癌及三阴性乳腺癌中的表达均明显低于正常乳腺组织,在乳腺癌中,DLL1在不同雌激素受体(ER)、孕激素受体(PR)状态、年龄、病理组织类型的表达差异有统计学意义(P <0.01);在不同人表皮生长因子2(HER2)状态,是否绝经、不同种族、有无远处转移、有无淋巴结转移的表达差异无统计学意义(P> 0.05)。在三阴性乳腺癌中,DLL1在年龄、病理组织、绝经、种族、远处转移、淋巴结转移各参数不同状态下的表达差异无统计学意义(P> 0.05)。DLL1表达越低,乳腺癌患者总生存时间和无病生存时间更短,但是在三阴性乳腺癌患者中,DLL1表达越低,乳腺癌患者无病生存时间更长。结论在乳腺癌和三阴性乳腺癌中,DLL1低表达并且与患者的预后相关,DLL1的表达与乳腺癌ER、PR、年龄、病理组织类型相关性差异有统计学意义,DLL1在乳腺癌的发生中可能起着重要作用。
Objective To detect the expression of DLL1 gene in breast cancer and triple-negative breastcancer,and to investigate the relationship between DLL1 expression,clinical data and prognosis. Methods Dataof breast cancer was collected from the tumor genome map(TCGA)database,as well as DLL1 gene expressionprofiles. The median was divided into the high expression group and the low expression group. The relationshipbetween the high expression group and the low expression group was analyzed,and the relationship between theclinical data and the case characteristics was analyzed by Kaplan-Meier Plotter assay. The correlation betweenDLL1 and the prognosis of patients with breast cancer was analyzed. Results Expression of DLL1 in breast cancerand triple-negative breast cancer was significantly lower than that of the normal breast tissue. In breast cancer,DLL1 expression was significantly related to ER,PR,age and pathological type,but with no significant correla-tion with HER2,menopause,race,distant metastasis and lymph node metastasis. In triple-negative breast cancergroup,DLL1 expression was not correlated with age,histopathology,menopause,race,distant metastasis andlymph node metastasis. The expression of DLL1 was lower,the total survival time and the disease-free survival timeof the patients with breast cancer were shorter. However,the expression of DLL1 in the triple-negative breast can-cer patients was lower,the disease-free survival time of patients was longer. Conclusions Low expression ofDLL1 in breast cancer and triple-negative breast cancer is associated with the prognosis of the patients. The expres-sion of DLL1 is significantly related to ER,PR,age and pathological type of breast cancer. DLL1 may play animportant role in the occurrence of breast cancer.
Objective To detect the expression of DLL1 gene in breast cancer and triple-negative breastcancer,and to investigate the relationship between DLL1 expression,clinical data and prognosis. Methods Dataof breast cancer was collected from the tumor genome map(TCGA)database,as well as DLL1 gene expressionprofiles. The median was divided into the high expression group and the low expression group. The relationshipbetween the high expression group and the low expression group was analyzed,and the relationship between theclinical data and the case characteristics was analyzed by Kaplan-Meier Plotter assay. The correlation betweenDLL1 and the prognosis of patients with breast cancer was analyzed. Results Expression of DLL1 in breast cancerand triple-negative breast cancer was significantly lower than that of the normal breast tissue. In breast cancer,DLL1 expression was significantly related to ER,PR,age and pathological type,but with no significant correla-tion with HER2,menopause,race,distant metastasis and lymph node metastasis. In triple-negative breast cancergroup,DLL1 expression was not correlated with age,histopathology,menopause,race,distant metastasis andlymph node metastasis. The expression of DLL1 was lower,the total survival time and the disease-free survival timeof the patients with breast cancer were shorter. However,the expression of DLL1 in the triple-negative breast can-cer patients was lower,the disease-free survival time of patients was longer. Conclusions Low expression ofDLL1 in breast cancer and triple-negative breast cancer is associated with the prognosis of the patients. The expres-sion of DLL1 is significantly related to ER,PR,age and pathological type of breast cancer. DLL1 may play animportant role in the occurrence of breast cancer.
引文
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[2] SHU S,LIN C Y,HE H H,et al. Response and resistance toBET bromodomain inhibitors in triple-negative breast cancer[J]. Nature,2016,529(7586):413-417.
[3] MOORE-SMITH L,FORERO-TORRES A,STRINGER-REA-SOR E. Future developments in neoadjuvant therapy for triple-negative breast cancer[J]. Surg Clin North Am,2018,98(4):773-785.
[4] LAMY M,FERREIRA A,DIAS J S,et al. Notch-out for breastcancer therapies[J]. N Biotechnol,2017,39(Pt B):215-221.
[5] BOURAS T,PAL B,VAILLANT F,et al. Notch signaling reg-ulates mammary stem cell function and luminal cell-fate commit-ment[J]. Cell Stem Cell,2008,3(4):429-441.
[6] OZAY E I,SHERMAN H L,MELLO V,et al. Rotenone treat-ment reveals a role for electron transport complex I in the subcel-lular localization of key transcriptional regulators during T Help-er cell differentiation[J]. Front Immunol,2018,9:1284.
[7] BIGAS A,ESPINOSA L. The multiple usages of Notch signal-ing in development,cell differentiation and cancer[J]. CurrOpin Cell Biol,2018,55:1-7.
[8] MAH I K,SOLOFF R,HEDRICK S M,et al. Atypical PKC-iotacontrols stem cell expansion via regulation of the Notch pathway[J]. Stem Cell Reports,2015,5(5):866-880.
[9] YUAN Q,CHEN X,HAN Y,et al. Modification of alpha2,6-sialylation mediates the invasiveness and tumorigenicity of non-small cell lung cancer cells in vitro and in vivo via Notch1/Hes1/MMPs pathway[J]. Int J Cancer,2018.
[10] SONG H Y,WANG Y,LAN H,et al. Expression of Notch re-ceptors and their ligands in pancreatic ductal adenocarcinoma[J]. Exp Ther Med,2018,16(1):53-60.
[11] JIN Z,ZHAN T,TAO J,et al. MicroRNA-34a induces transdif-ferentiation of glioma stem cells into vascular endothelial cellsby targeting Notch pathway[J]. Biosci Biotechnol Biochem,2017,81(10):1899-1907.
[12] CHAKRABARTI R,CELIA-TERRASSA T,KUMAR S,et al.Notch ligand Dll1 mediates cross-talk between mammary stemcells and the macrophageal niche[J]. Science,2018,360(6396).pii:eaan4153.