目的探讨乙酰化STAT3对DIRAS2基因表达的调控及其在三阴性乳腺癌(triple-negative breast cancer,TNBC)细胞增殖中的作用。方法通过数据库查询、Western blotting和qRT-PCR分析TNBC组织和细胞中DIRAS2和乙酰化STAT3的表达水平。选取TNB...目的探讨乙酰化STAT3对DIRAS2基因表达的调控及其在三阴性乳腺癌(triple-negative breast cancer,TNBC)细胞增殖中的作用。方法通过数据库查询、Western blotting和qRT-PCR分析TNBC组织和细胞中DIRAS2和乙酰化STAT3的表达水平。选取TNBC细胞系MDA-MB-231和SUM159,通过慢病毒或质粒构建DIRAS2过表达及STAT3野生或Lys685位点突变的细胞株。利用CCK-8实验评估DIRAS2和STAT3乙酰化对TNBC细胞增殖的影响。应用Western blotting、焦磷酸测序、ChIP和IP技术研究乙酰化STAT3对DIRAS2表达的调控作用及机制。结果DIRAS2在TNBC组织和细胞中表达较低。焦磷酸测序分析发现,与正常乳腺上皮细胞相比,TNBC细胞中DIRAS2启动子区域的CpG岛甲基化水平升高,并促进癌细胞增殖。此外,TNBC细胞中STAT3的乙酰化程度增加,而DIRAS2启动子甲基化状态随着STAT3乙酰化的增加而发生改变。ChIP和IP实验表明,乙酰化STAT3可与DIRAS2启动子结合,而STAT3 Lys685位点突变会破坏STAT3与DNMT1的相互作用。结论在TNBC中,乙酰化STAT3通过招募DNMT1诱导DIRAS2基因启动子甲基化,从而导致DIRAS2表达缺失和癌细胞增殖。展开更多
目的:通过检测三阴性乳腺癌(triple-negative breast cancer,TNBC)组织中肿瘤相关中性粒细胞(tumor-associated neutrophils,TANs)浸润密度及程序性死亡配体-1(PD-L1)的表达情况来分析二者的相关性,并探究其临床意义。方法:选取141例我...目的:通过检测三阴性乳腺癌(triple-negative breast cancer,TNBC)组织中肿瘤相关中性粒细胞(tumor-associated neutrophils,TANs)浸润密度及程序性死亡配体-1(PD-L1)的表达情况来分析二者的相关性,并探究其临床意义。方法:选取141例我院三阴性乳腺癌患者组织标本,使用抗体CD66b作为TANs的标记物,通过免疫组织化学法检测TNBC肿瘤组织内TANs浸润和PD-L1表达的情况。采用Pearson积差相关或Spearman等级相关分别分析TANs浸润密度和PD-L1表达与临床病理特征的相关性,以及TNBC肿瘤组织内TANs浸润密度与PD-L1阳性表达之间的相关性;采用Kaplan-Meier曲线对TNBC患者进行生存分析。结果:TANs高浸润密度与高Ki67增殖指数、高组织学分级以及淋巴结转移均呈正相关(P<0.05)。PD-L1表达与高Ki67增殖指数及高组织学分级均呈正相关(P<0.05)。TNBC中TANs的浸润密度与PD-L1阳性表达呈正相关(P<0.05)。生存分析显示,TANs浸润密度和PD-L1表达均与TNBC患者的无进展生存期呈负相关(P<0.05)。结论:TNBC肿瘤组织内TANs浸润密度和PD-L1表达与多项临床病理特征以及不良预后密切相关,这提示TANs及PD-L1可作为TNBC预后评估的重要指标,并为探索TNBC免疫治疗潜在靶点提供研究依据。展开更多
三阴性乳腺癌(TNBC)是一种侵袭性乳腺癌亚型,通常以缺乏雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体-2 (HER2)为特征,约占所有乳腺癌的15%~20%。与其他分子表型相比,TNBC通常与高恶性和不良预后相关。在DNA水平上整合组学知识...三阴性乳腺癌(TNBC)是一种侵袭性乳腺癌亚型,通常以缺乏雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体-2 (HER2)为特征,约占所有乳腺癌的15%~20%。与其他分子表型相比,TNBC通常与高恶性和不良预后相关。在DNA水平上整合组学知识,进一步扩大了对乳腺癌的生物学认识,这是临床上三阴性肿瘤的迫切需求。由于缺乏明确的靶点和有限的治疗干预措施,细胞毒性药物在过去几十年中一直是治疗的主要手段。然而,最近的发展表明,TNBC具有特殊的分子分类和生物标志物,这为从基本的细胞毒性化疗发展到扩大靶向治疗领域提供了可能性。随着检测技术的不断发展和对TNBC分子亚型研究的不断深入,出现了针对免疫检查点和不同靶点的药物,如抗体–药物偶联物等。这些疗法为TNBC的治疗提供了新的希望。本文在对TNBC进行分析和分类的基础上,总结了免疫治疗与新的治疗组合,为今后TNBC的精准治疗提供参考。Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is typically characterized by a lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) and accounts for approximately 15% to 20% of all breast cancers. TNBC is often associated with high malignancy and poor prognosis compared to other molecular phenotypes. Integrating omics knowledge at the DNA level further expands the biological understanding of breast cancer, which is urgently needed in the clinical setting of triple-negative tumors. Due to the lack of clear targets and limited therapeutic interventions, cytotoxic drugs have been the mainstay of treatment in the past decades. However, recent developments have shown that TNBC has a specific molecular classification and biomarkers, which opens up the possibility of moving from basic cytotoxic chemotherapy to expanding the field of targeted therapy. With the continuous development of detection technology and the deepening of research on the molecular subtypes of TNBC, drugs targeting immune checkpoints and different targets, such as antibody-drug conjugates, have emerged. These therapies provide new hope for the treatment of TNBC. Based on the analysis and classification of TNBC, this article summarizes the immunotherapy and new treatment combinations, so as to provide reference for the precise treatment of TNBC in the future.展开更多
目的探讨三阴性乳腺癌(triple negative breast cancer TNBC)患者临床、病理和预后的特点。方法回顾性研究2005年3月一2009年9月期间就诊于新疆医科大学附属肿瘤医院,有完整临床病理资料的319例可手术I^ID期TNBC和Luminal型乳腺癌患者...目的探讨三阴性乳腺癌(triple negative breast cancer TNBC)患者临床、病理和预后的特点。方法回顾性研究2005年3月一2009年9月期间就诊于新疆医科大学附属肿瘤医院,有完整临床病理资料的319例可手术I^ID期TNBC和Luminal型乳腺癌患者的病历资料,搜集患者的一般资料、月经及生育状况、病理资料、治疗情况并进行随访,分析TNBC的临床病理和预后特征。计数资料的比较采用卡方检验,生存分析使用Log-rank检验。结果319例乳腺癌患者共随访9〜86个月,中位随访时间72个月。其中TNBC共103例,Luminal型乳腺癌共216例。与Luminal型乳腺癌相对比,TNBC病理结果为单一成分比混合成分更常见(P=0.025),其中髓样癌更多为TNBC(P=0.000)o TNBC中原发肿瘤大于T1的患者多于T1患者(P=0.036),腋窝淋巴结转移数目差异无统计学意义(P>0.05)。TNBC中Ki-67表达无统计学差异(P>0.05),但nm23表达为阴性者较多(P=0.006)。TNBC和Luminal型乳腺癌3年总生存率(overall survival OS)分别是91.1%和96.7%,5年OS分别为86.9%和93.8%,差异无统计学意义(P=0.066)o TNEC和Luminal型乳腺癌3年无病生存率disease free survival DFS)分别是79.9%和92.5%,5年DFS分别为76.0%和87.0%,差异有统计学意义(P=0.013)。影响TNBC无病生存率的独立预后因素包括族别、nm23的表达情况和病期(P V0.05)。结洽TNBC具有病理成分单一,肿瘤体积大,nm23表达缺失,无病生存率较低,在维吾尔族中更易复发和转移的特点。展开更多
Background: Epigenetic mechanisms including DNA methylation are key regulators of gene activity and may play key roles in carcinogenesis through cumulative activation and inactivation of oncogenes, tumor suppressor ge...Background: Epigenetic mechanisms including DNA methylation are key regulators of gene activity and may play key roles in carcinogenesis through cumulative activation and inactivation of oncogenes, tumor suppressor genes, and other genes. Increased vimentin gene expression has been reported in various tumor cell lines and tissues including breast cancer. In addition, methylation of the vimentin gene was described as a marker in several malignant tumors. Objective: The aim of this study is to determine the existence of a potential relationship between the methylation state of the vimentin gene and its prognostic value in breast cancer patients and its correlation with vimentin protein expression in the serum. Patients and Methods: The methylation status of the vimentin gene was examined in primary infiltrating ductaltumors and the surrounding normal tissues derived from 50 breast cancer patients enrolled for either modified radical mastectomy or conservative breast surgery using quantitative methylation-specific polymerase chain reaction (qMSP), serum vimentin levels were determined using ELISA, and the correlation between the methylation status and the clinicopathological findings was evaluated. Results: Out of 50 breast cancer patients, 18 (36%) exhibited positive methylation of vimentin gene while 32 (64%) exhibited negative vimentin genemethylation in their tumors. Subsequently clinicopathological data were correlated with the vimentin genemethylation score. A significant association was found between negative vimentin methylation, and both serum vimentin protein level (p 0.001) and the triple negative breast cancer subtype (TNBCs) (p = 0.004). Using receiver-operating characteristic (ROC) curve analysis, a cut off value of <0.49 was set for the negative vimentin methylation score to distinguish between early and late stage breast cancer, and the ROC curve showed an area under the curve (AUC) of 0.684 (p = 0.029). Conclusion: Our study showed that the vimentin gene is frequently hypomethylated in breast cancer tissues, and that negative methylation status is always associated with high serum vimentin protein expression levels. Also we reported a significant association between negative vimentin methylation and TNBC subtype which is known to have an aggressive clinical course. Taken together, these results might have important implications for the design of novel therapeutic interventions for breast cancer patients. However, further studies with larger sample size are needed to validate these observations.展开更多
目的研究乳腺癌易感基因1(Breast cancer susceptibility gene 1,BRCA1)在三阴性乳腺癌(Triple-negative breast cancer,TNBC)中的表达及与临床预后的关系。方法使用PubMed、西文生物医学、万方、维普以及CNKI检索平台对相关文献进行检...目的研究乳腺癌易感基因1(Breast cancer susceptibility gene 1,BRCA1)在三阴性乳腺癌(Triple-negative breast cancer,TNBC)中的表达及与临床预后的关系。方法使用PubMed、西文生物医学、万方、维普以及CNKI检索平台对相关文献进行检索,设置检索年限范围为2010年1月至2019年5月,整理公开发表于该期间的关于TNBC患者BRCA1表达与预后情况的高质量研究成果。使用Review Manager 5.3对符合标准的研究结果进Meta分析。结果本文共纳入文献18篇,涵盖患者19802人(TNBC患者3431人;non-TNBC患者16371人)。Meta分析结果显示,TNBC患者群体BRCA1阳性表达率显著高于non-TNBC患者群体(OR=1.85,95%CI:1.55~2.21,P=0.001);TNBC患者群体中,淋巴结转移(+)的群体BRCA1阳性表达率显著低于淋巴结转移(-)患者(OR=0.61,95%CI:0.44~0.86,P=0.02);TNBC患者中,TNM分期TI^TII期患者群体BRCA1阳性表达率高于TIII^TIV期患者(OR=2.75,95%CI:1.42~7.47,P=0.03);TNBC患者五年生存率与BRCA1的表达水平无关(OR=0.92,95%CI:0.60~1.41,P=0.39)。结论与non-TNBC患者相比,BRCA1在TNBC患者中高表达,提示BRCA1可能是影响TNBC患者淋巴结转移和肿瘤TNM分期等预后指标的重要因素。展开更多
探讨细胞程序性死亡配体1(Programmed death ligand 1,PD-L1)与三阴性乳腺癌(Triple negative breast cancer,TNBC)临床病理的相关性,为TNBC患者的预后及治疗提供参考。收集我院88例经病理确诊为TNBC患者的病理组织,利用PD-L1抗体检测试...探讨细胞程序性死亡配体1(Programmed death ligand 1,PD-L1)与三阴性乳腺癌(Triple negative breast cancer,TNBC)临床病理的相关性,为TNBC患者的预后及治疗提供参考。收集我院88例经病理确诊为TNBC患者的病理组织,利用PD-L1抗体检测试剂,通过免疫组化的方法,将TNBC病理组织制片并在显微镜下观察;采用统计学方法进行分析,研究PD-L1与TNBC临床病理特征的相关性。结果:88例TNBC患者中,共检出23例(26.1%)PD-L1阳性。PD-L1表达与患者的年龄、绝经状态和肿瘤大小、发生部位、脉管瘤栓、表皮生长因子受体、Ki-67、身体质量指数(BMI)无统计学相关(P>0.05),与淋巴结转移、高组织学分级和角蛋白5/6(CK5/6)表达有着显著相关(P<0.05)。结果表明,PD-L1表达一定程度上与TNBC患者的预后相关,但在预测预后方面仍存在一定的不足。展开更多
文摘目的:通过检测三阴性乳腺癌(triple-negative breast cancer,TNBC)组织中肿瘤相关中性粒细胞(tumor-associated neutrophils,TANs)浸润密度及程序性死亡配体-1(PD-L1)的表达情况来分析二者的相关性,并探究其临床意义。方法:选取141例我院三阴性乳腺癌患者组织标本,使用抗体CD66b作为TANs的标记物,通过免疫组织化学法检测TNBC肿瘤组织内TANs浸润和PD-L1表达的情况。采用Pearson积差相关或Spearman等级相关分别分析TANs浸润密度和PD-L1表达与临床病理特征的相关性,以及TNBC肿瘤组织内TANs浸润密度与PD-L1阳性表达之间的相关性;采用Kaplan-Meier曲线对TNBC患者进行生存分析。结果:TANs高浸润密度与高Ki67增殖指数、高组织学分级以及淋巴结转移均呈正相关(P<0.05)。PD-L1表达与高Ki67增殖指数及高组织学分级均呈正相关(P<0.05)。TNBC中TANs的浸润密度与PD-L1阳性表达呈正相关(P<0.05)。生存分析显示,TANs浸润密度和PD-L1表达均与TNBC患者的无进展生存期呈负相关(P<0.05)。结论:TNBC肿瘤组织内TANs浸润密度和PD-L1表达与多项临床病理特征以及不良预后密切相关,这提示TANs及PD-L1可作为TNBC预后评估的重要指标,并为探索TNBC免疫治疗潜在靶点提供研究依据。
文摘三阴性乳腺癌(TNBC)是一种侵袭性乳腺癌亚型,通常以缺乏雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体-2 (HER2)为特征,约占所有乳腺癌的15%~20%。与其他分子表型相比,TNBC通常与高恶性和不良预后相关。在DNA水平上整合组学知识,进一步扩大了对乳腺癌的生物学认识,这是临床上三阴性肿瘤的迫切需求。由于缺乏明确的靶点和有限的治疗干预措施,细胞毒性药物在过去几十年中一直是治疗的主要手段。然而,最近的发展表明,TNBC具有特殊的分子分类和生物标志物,这为从基本的细胞毒性化疗发展到扩大靶向治疗领域提供了可能性。随着检测技术的不断发展和对TNBC分子亚型研究的不断深入,出现了针对免疫检查点和不同靶点的药物,如抗体–药物偶联物等。这些疗法为TNBC的治疗提供了新的希望。本文在对TNBC进行分析和分类的基础上,总结了免疫治疗与新的治疗组合,为今后TNBC的精准治疗提供参考。Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is typically characterized by a lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) and accounts for approximately 15% to 20% of all breast cancers. TNBC is often associated with high malignancy and poor prognosis compared to other molecular phenotypes. Integrating omics knowledge at the DNA level further expands the biological understanding of breast cancer, which is urgently needed in the clinical setting of triple-negative tumors. Due to the lack of clear targets and limited therapeutic interventions, cytotoxic drugs have been the mainstay of treatment in the past decades. However, recent developments have shown that TNBC has a specific molecular classification and biomarkers, which opens up the possibility of moving from basic cytotoxic chemotherapy to expanding the field of targeted therapy. With the continuous development of detection technology and the deepening of research on the molecular subtypes of TNBC, drugs targeting immune checkpoints and different targets, such as antibody-drug conjugates, have emerged. These therapies provide new hope for the treatment of TNBC. Based on the analysis and classification of TNBC, this article summarizes the immunotherapy and new treatment combinations, so as to provide reference for the precise treatment of TNBC in the future.
文摘Background: Epigenetic mechanisms including DNA methylation are key regulators of gene activity and may play key roles in carcinogenesis through cumulative activation and inactivation of oncogenes, tumor suppressor genes, and other genes. Increased vimentin gene expression has been reported in various tumor cell lines and tissues including breast cancer. In addition, methylation of the vimentin gene was described as a marker in several malignant tumors. Objective: The aim of this study is to determine the existence of a potential relationship between the methylation state of the vimentin gene and its prognostic value in breast cancer patients and its correlation with vimentin protein expression in the serum. Patients and Methods: The methylation status of the vimentin gene was examined in primary infiltrating ductaltumors and the surrounding normal tissues derived from 50 breast cancer patients enrolled for either modified radical mastectomy or conservative breast surgery using quantitative methylation-specific polymerase chain reaction (qMSP), serum vimentin levels were determined using ELISA, and the correlation between the methylation status and the clinicopathological findings was evaluated. Results: Out of 50 breast cancer patients, 18 (36%) exhibited positive methylation of vimentin gene while 32 (64%) exhibited negative vimentin genemethylation in their tumors. Subsequently clinicopathological data were correlated with the vimentin genemethylation score. A significant association was found between negative vimentin methylation, and both serum vimentin protein level (p 0.001) and the triple negative breast cancer subtype (TNBCs) (p = 0.004). Using receiver-operating characteristic (ROC) curve analysis, a cut off value of <0.49 was set for the negative vimentin methylation score to distinguish between early and late stage breast cancer, and the ROC curve showed an area under the curve (AUC) of 0.684 (p = 0.029). Conclusion: Our study showed that the vimentin gene is frequently hypomethylated in breast cancer tissues, and that negative methylation status is always associated with high serum vimentin protein expression levels. Also we reported a significant association between negative vimentin methylation and TNBC subtype which is known to have an aggressive clinical course. Taken together, these results might have important implications for the design of novel therapeutic interventions for breast cancer patients. However, further studies with larger sample size are needed to validate these observations.
文摘目的研究乳腺癌易感基因1(Breast cancer susceptibility gene 1,BRCA1)在三阴性乳腺癌(Triple-negative breast cancer,TNBC)中的表达及与临床预后的关系。方法使用PubMed、西文生物医学、万方、维普以及CNKI检索平台对相关文献进行检索,设置检索年限范围为2010年1月至2019年5月,整理公开发表于该期间的关于TNBC患者BRCA1表达与预后情况的高质量研究成果。使用Review Manager 5.3对符合标准的研究结果进Meta分析。结果本文共纳入文献18篇,涵盖患者19802人(TNBC患者3431人;non-TNBC患者16371人)。Meta分析结果显示,TNBC患者群体BRCA1阳性表达率显著高于non-TNBC患者群体(OR=1.85,95%CI:1.55~2.21,P=0.001);TNBC患者群体中,淋巴结转移(+)的群体BRCA1阳性表达率显著低于淋巴结转移(-)患者(OR=0.61,95%CI:0.44~0.86,P=0.02);TNBC患者中,TNM分期TI^TII期患者群体BRCA1阳性表达率高于TIII^TIV期患者(OR=2.75,95%CI:1.42~7.47,P=0.03);TNBC患者五年生存率与BRCA1的表达水平无关(OR=0.92,95%CI:0.60~1.41,P=0.39)。结论与non-TNBC患者相比,BRCA1在TNBC患者中高表达,提示BRCA1可能是影响TNBC患者淋巴结转移和肿瘤TNM分期等预后指标的重要因素。
文摘探讨细胞程序性死亡配体1(Programmed death ligand 1,PD-L1)与三阴性乳腺癌(Triple negative breast cancer,TNBC)临床病理的相关性,为TNBC患者的预后及治疗提供参考。收集我院88例经病理确诊为TNBC患者的病理组织,利用PD-L1抗体检测试剂,通过免疫组化的方法,将TNBC病理组织制片并在显微镜下观察;采用统计学方法进行分析,研究PD-L1与TNBC临床病理特征的相关性。结果:88例TNBC患者中,共检出23例(26.1%)PD-L1阳性。PD-L1表达与患者的年龄、绝经状态和肿瘤大小、发生部位、脉管瘤栓、表皮生长因子受体、Ki-67、身体质量指数(BMI)无统计学相关(P>0.05),与淋巴结转移、高组织学分级和角蛋白5/6(CK5/6)表达有着显著相关(P<0.05)。结果表明,PD-L1表达一定程度上与TNBC患者的预后相关,但在预测预后方面仍存在一定的不足。
