Clinical significance of breast cancer susceptibility gene 1 expression in resected non-small cell lung cancer:A meta-analysis

BACKGROUND The clinical significance of breast cancer susceptibility gene 1(BRCA1)in nonsmall cell lung cancer(NSCLC)patients undergoing surgery remains unclear up to now.AIM To explore the relation of BRCA1 expression with clinicopathological characteristics and survival in patients with resected NSCLC.METHODS EMBASE,PubMed,Web of Science,and The Cochrane Library databases were searched to identify the relevant articles.To assess the correlation between the expression of BRCA1 and clinicopathological characteristics and prognosis of patients with resected NSCLC patients,the combined relative risks or hazard ratios(HRs)with their corresponding 95%confidence intervals[CIs]were estimated.RESULTS Totally,11 articles involving 1041 patients were included in the meta-analysis.The results indicated that the expression of BRCA1 was significantly correlated with prognosis of resected NSCLC.Positive BRCA1 expression signified a shorter overall survival(HR=1.60,95%CI:1.25-2.05;P<0.001)and disease-free survival(HR=1.78,95%CI:1.42-2.23;P<0.001).However,no significant association of BRCA1 expression with any clinicopathological parameters was observed.CONCLUSION BRCA1 expression indicates a poor prognosis in resected NSCLC patients.BRCA1 might serve as an independent biomarker to predict clinical outcomes and help to customize optimal adjuvant chemotherapy for NSCLC patients who had received surgical therapy.

Molecular Docking Studies of Botanical Beverage Mix Berries (LIFEGREENTM) against Breast Cancer Cells from Targeted Protein 1QQG, 7B5Q & 7B5O & Uterine Fibroid from Targeted Protein 2AYR, 6T41 & 3GRF

Fibroids, also called leiomyomas or myomas, are communal tumors of the muscle or uterine wall that affect about 20% of females who are of reproductive age. They can look as if singly or in clusters, and they often cease to grow after menopause. Fibroids can be classified as intramural, sub serosal, pedunculated, or submucosal based on where they are positioned in the uterus. Although fibroids are benign, they can grow quickly and cause a range of symptoms, such as pelvic pressure, heavy menstrual flow, and infertility. As a result, fibroids are a main reason behind hysterectomy surgeries. The majority of cases of breast cancer are ductal and lobular cancers, making it the second utmost common cancer in women international. Gene mutations like those in BRCA1 or BRCA2 knowingly raise the risk of breast and other cancers, typically with an earlier cancer onset. Cancer risk is influenced by a complex interplay of genetic abnormalities, environmental factors, and lifestyle selections. Further research into these relations is domineering. Although they are common in uterine leiomyomas, especially multiple leiomyomas, MED12 mutations do not significantly correlate with tumor size. These mutations have also been noticed in smooth muscle tumors and leiomyosarcomas, two other types of uterine cancer. The identification of MED12 mutations as the sole genetic abnormality originates in leiomyomas raises the opportunity of a role in the genesis of cancer. 10% - 15% of women who are of reproductive age have endometriosis, which grants serious difficulties because of its chronic nature and range of clinical symptoms. Even after effective surgeries, issues reoccur often, adding to the enormous financial burden. The effects of MED12 mutations have been experiential in recent studies examining the molecular causes of endometriosis-associated infertility, which have shown anomalies in cellular connections and signaling cascades. Computational techniques were used in this study to investigate LifeGreenTM’s potential to prevent uterine fibroids and breast cancer. The efficacy of LifeGreenTM as a preventive measure or a treatment for common gynecological matters was examined and modeled. We investigated the mechanisms underlying LifeGreenTM’s benefits in the treatment of uterine fibroids and breast cancer using computational techniques. Our research contributes to our understanding of its potential therapeutic benefits for women’s health.

Research progress on the relationship between BRCA1 and hereditary breast cancer

Breast cancer gene 1(BRCA1) gene was the first breast cancel susceptibility gene discovered in familial breast cancer.It has been revealed that BRCA1 can be combined with an array of important protein involved in cell cycle regulation,DNA repair,gene transcription control and apoptosis regulation.It plays a down-regulation effect on tumor growth and an important role in maintaining genomic stability.New research suggests that it also associate with the breast cancer stem cells and microRNA.Its mutations,promoter methylation and ectopic expression may one of the main reasons for the generation and development of hereditary breast cancer.

Cancer risk in relatives of BRCA1/2 pathogenic variant carriers in a large series of unselected patients with breast cancer

Objective:The spectrum and risk of cancer in relatives of BRCA1/2 pathogenic variant carriers in the Chinese population have not been established.Methods:A family history of cancer in 9903 unselected breast cancer patients was retrospectively analyzed.BRCA1/2 status was determined for all patients and relative risks(RRs)were calculated to evaluate cancer risk in relatives of the patients.Results:The incidences of breast cancer in female relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 33.0%,32.2%,and 7.7%,respectively.The corresponding incidences of ovarian cancer were 11.5%,2.4%,and 0.5%,respectively.The incidences of pancreatic cancer in male relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 1.4%,2.7%,and 0.6%,respectively.The corresponding incidences of prostate cancer were 1.0%,2.1%,and 0.4%,respectively.The risks of breast and ovarian cancers in female relatives of BRCA1 and BRCA2 carriers were significantly higher than female relatives of non-carriers(BRCA1:RR=4.29,P<0.001 and RR=21.95,P<0.001;BRCA2:RR=4.19,P<0.001 and RR=4.65,P<0.001,respectively).Additionally,higher risks of pancreatic and prostate cancers were noted in male relatives of BRCA2 carriers than non-carriers(RR=4.34,P=0.001 and RR=4.86,P=0.001,respectively).Conclusions:Female relatives of BRCA1 and BRCA2 carriers are at increased risk for breast and ovarian cancers,and male relatives of BRCA2 carriers are at increased risk for pancreatic and prostate cancers.

BRCA1 and EGFR as prognostic biomarkers in triple negative metastatic breast cancer patients treated with cisplatin plus docetaxel

Objective： The triple negative （TN） metastatic breast cancer （MBC） patients are known to have worse prognosis, shorter progressive free survival （PFS）, and overall survival （OS）, that mandates using aggressive chemotherapy regimens. This phase II study aimed at investigating the efficacy and safety of using cisplatin and docetaxel in patients with triple negative metastatic breast cancer, and the possibility of using breast cancer susceptibility genel （BRCA1） expression as a predictive marker of chemotherapy response, and epidermal growth factor receptor （EGFR） as prognostic marker. Method： Between January 2006 and March 2009, 40 eligible patients with TN MBC were included in the study. We examined BRCA1 expression and EGFR protein in their specimens using immunohistochemistry. The patients were treated with cisplatin 75 mg/m2 and docetaxel 75 mg/m2 every 3 weeks, TN measurable MBC patients previously treated with anthracycline in their adjuvant or neo adjuvant settings were included in the study. Results： The median age of the treated patients was 43.5 years. Nearly half of the patients had an ECOG performance status of 0 or 1, and about third of them had one metastatic site. These metastatic sites were predominantly visceral in 80% of the patients. Fifty-five percent of TNMBC stained positive for BRCA1 and sixty-five percent for EGFR. Positivity for both markers was significantly associated with grade III tumors （P = 0.004）, OS, and PFS （P = 0.001 and 0.009） respectively. Overall, the regimen was well tolerated as Gill vomiting and neurological side effects were observed in 20% of the patients. Other toxiciUes were generally mild and medically manageable; with no treatment mortality was recorded. The overall disease control rate （ODCR） was 60%; the median PFS was 8 months, with a median overall OS of 17.5 months; while the median OS among responders was 23 months （95% CI 21.35 to 25.32）. The patients with negative EGFR had a significantly better OR, PFS, and OS than EGFR positive cases. There was no significant difference concerning OR, PFS, and OS, between positive and negative BRCA1 cases, which could be attributed to the better efficacy of cisplatin in the positive BRCA1 cases. Conclusion： This chemotherapy regimen is effective with tolerable toxicity profile, our results point out the importance of BRCA1 expression as predictive marker of chemotherapy response, and EGFR as prognostic marker, which could identify a certain group of patients with more aggressive disease who might benefit from using anti EGFR targeted therapy plus cisplatin.

Detection of Breast Cancer 1 (BRCA1) Gene Using an Electrochemical DNA Biosensor Based on Immobilized ZnO Nanowires

Herein we report an electrochemical DNA biosensor for the rapid detection of sequence (5’ AAT GGA TTT ATC TGC TCT TCG 3’) specific for the breast cancer 1 (BRCA1) gene. The proposed electrochemical genosensor is based on short oligonucleotide DNA probe immobilized onto zinc oxide nanowires (ZnONWs) chemically synthesized onto gold electrode via hydrothermal technique. The morphology studies of the ZnONWs, performed by field emission scanning electron microscopy (FESEM), showed that the ZnO nanowires are uniform, highly dense and oriented perpendicularly to the substrate. Recognition event between the DNA probe and the target was investigated by differential pulse voltammetry (DPV) in 0.1 M acetate buffer solution (ABS), pH 7.00;as a result of the hybridization, an oxidation signal was observed at +0.8 V. The influences of pH, target concentration, and non-complimentary DNA on biosensor performance were examined. The proposed DNA biosensor has the ability to detect the target sequence in the range of concentration between 10.0 and 100.0 μM with a detection limit of 3.32 μM. The experimental results demonstrated that the prepared ZnONWs/Au electrodes are suitable platform for the immobilization of DNA.

Review:BRCA1/2 associated hereditary breast cancer

Breast cancer is one of the leading causes of death in women today. Some of the patients are hereditary, with a large proportion characterized by mutation in BRCAI and/or BRCA2 genes. In this review, we provide an overview of these two genes, focusing on their relationship with hereditary breast cancers. BRCA1/2 associated hereditary breast cancers have unique features that differ from the general breast cancers, including alterations in cellular molecules, pathological bases, biological behavior, and a different prevention strategy. But the outcome of BRCA1/2 associated hereditary breast cancers still remains controversial; further studies are needed to elucidate the nature of BRCA 1/2 associated hereditary breast cancers.

The Role of HER2/Neu and BRCA1 Genes in the Diagnosis of Breast Cancer among Sudanese Women

Background: Knowledge of HER2/Neu and BRCA1 Genes might be helpful for development of strategies for decreasing the burden of risk of breast cancer. Therefore, the aim of this study to detect the role of HER2/Neu and BRCA1 Genes expression in diagnosis of breast cancer in Sudanese women. Methodology: A total of 100 tissue samples obtained from patients with breast cancer in addition to 50 tissue samples obtained from patients with benign breast lesions, were detected the expression of HER2/Neu and BRCA1 Genes by Polymerase Chain Reaction (PCR). Results: The prevalence of HER2/Neu and BRCA1 Genes, among cases was 6%, and 10% respectively. Conclusion: HER2/Neu and BRCA1 Genes have a considerable contribution to etiology of breast cancer in Sudan that requires further consideration.

BRCA1、BRCA2在上皮性卵巢癌中的表达及与预后的关系

目的 探讨乳腺癌易感基因1(BRCA1)、乳腺癌易感基因2(BRCA2)在上皮性卵巢癌(EOC)中的表达水平,并分析其与预后的关系。方法 选取2019年1月—2023年6月南通市肿瘤医院收治的98例EOC患者,采集术中切除的新鲜癌组织和癌旁组织,采用实时定量聚合酶链反应(qRT-PCR)检测组织中BRCA1、BRCA2 mRNA表达情况,分析其与临床病理特征的关系,并以Kaplan-Meier生存曲线和Cox回归模型分析其对EOC患者总生存期(OS)和无进展生存期(PFS)的影响。结果 EOC组织BRCA1、BRCA2 mRNA表达量、蛋白相对表达量均低于癌旁组织(P<0.05)。腹腔积液量≥500 mL、国际妇产科学联合会(FIGO)分期Ⅲ—Ⅳ期、有淋巴结转移患者的BRCA1、BRCA2 mRNA表达低于无腹腔积液和腹腔积液量<500 mL、FIGO分期Ⅰ—Ⅱ期及无淋巴结转移患者(P<0.05)。中位随访时间27(9~50)个月,随访率95.92%(4例失访),随访期间39例(39.80%)复发,26例(26.53%)死亡。Kaplan-Meier生存分析显示,BRCA1、BRCA2 mRNA高表达者累积生存率高于低表达者(P<0.05)。BRCA1、BRCA2 mRNA高表达者累积无进展生存率高于低表达者(P<0.05)。多因素Cox回归分析显示化疗≤6疗程、腹腔积液量≥500 mL、FIGO分期Ⅲ+Ⅳ期及BRCA1、BRCA2 mRNA低表达是影响EOC患者OS的独立危险因素(P<0.05)。术后残灶>2 cm、化疗≤6疗程、腹腔积液量≥500 mL及BRCA1、BRCA2 mRNA低表达是影响EOC患者PFS的独立危险因素(P<0.05)。结论 EOC癌变组织中BRCA1、BRCA2异常低表达,BRCA1、BRCA2 mRNA低表达与患者的临床病理特征关系密切,且影响患者PFS及OS。

不同临床病理特征卵巢浆液性肿瘤患者E-cadherin、BRCA1及P53的表达变化研究

目的:探究不同卵巢浆液性肿瘤中E-钙黏蛋白(E-cadherin)、乳腺癌易感基因1(BRCA1)、P53的表达变化情况。方法:选取2017年12月—2022年2月赣州市妇幼保健院的50例卵巢浆液性癌患者为A组,同时期的40例卵巢交界性浆液性肿瘤患者为B组,30例卵巢良性浆液性囊腺瘤患者为C组。检测及比较三组的组织E-cadherin、BRCA1、P53表达情况,并比较A组中不同年龄、淋巴结转移情况、FIGO分期及不同病理分级者的检测结果。结果:A组的E-cadherin及BRCA1阳性率显著均低于B组及C组,B组则显著均低于C组(P<0.05);A组P53阳性率显著高于B组及C组,B组则显著高于C组(P<0.05)。A组中低级别浆液性癌者E-cadherin和BRCA1阳性率均高于高级别浆液性癌者,低级别浆液性癌者P53阳性率显著低于高级别浆液性癌者,差异均有统计学意义(P<0.05)。A组中不同年龄及FIGO分期者的组织E-cadherin、BRCA1及P53阳性率比较,差异均无统计学意义(P>0.05)。A组有淋巴结转移者E-cadherin和BRCA1阳性率均低于无淋巴结转移者,有淋巴结转移者P53阳性率高于无淋巴结转移者,差异均有统计学意义(P<0.05)。结论:卵巢浆液性癌患者中E-cadherin及BRCA1呈低表达,而P53呈高表达,且不同临床病理情况者存在差异,因此在卵巢浆液性癌的早期筛查检测中有一定的参考价值。

BRCA1在胃癌组织的表达及对铂类药物预后的Meta分析

目的:通过Meta分析方法探究乳腺癌易感基因1(BRCA1)在胃恶性肿瘤组织中的表达以及铂类化疗药物治疗后的预后。方法:检索中国知网、PubMed、Embase、万方、维普等数据库中搜索关键词“乳腺癌易感基因1(BRCA1)”“胃恶性肿瘤”“表达”“铂类化疗药物”“预后”等关键词,筛选文献后记录纳入文献的一般情况及数据,采用RevMan.5.4软件进行Meta分析统计。结果:最终纳入12篇参考文献,包含2826例患者数据。将优势比(OR)和95%置信区间(95%CI)视为效应指标,经分析统计得出,BRCA1在不同浸润深度胃癌组织中、在有无淋巴结转移、在不同分化程度、在临床TNM分期中表达存在差异(P<0.05),且与肿瘤直径存在关联(P<0.05);术后行铂类药物化疗后3年无病生存率(disease free survival,DFS)以及总生存率(overall survival,OS),BRCA1阴性患者高于阳性患者。结论:BRCA1与胃癌组织临床病理特征存在相关性,此基因影响铂类化疗药物对胃癌治疗的疗效及预后。

The mechanism of BRCA1 participate sporadic breast carcinomas genesis

Objective To elucidate the BRCA1 participated mechanism of genesis and development of sporadic breast cancer through detect the statues of BRCA1 and analysis the relationship with the pathologic and clinic parameters.Methods BRCA1 statues were respectively analyzed in frozen samples or paraffine fixed sporadic breast carcinoma and benign breast tissues by three methods:protein expression by immunohistochemistry(IHC),the methylation of BRCA1 promoter by methylation specific PCR(MSP),gene copy number by interphase fluorescence in situ hybridization(FISH).Results 14.2%(29/204)cases were detected hypermethylation of BRCA1 promoter in sporadic breast cancer.BRCA1 mean copy number in sporadic breast cancer(1.70±0.14)less than those in benign tissues(2.03±0.08,P<0.05),and in sporadic breast cancer with hypermethylation of BRCA1(1.62±0.09)significantly less than in those without hypermethylation(1.84±0.26,P<0.05).The loss copy related to the methylation of BRCA1 promoter.There were significant of 41.1%(88/214)cases no BRCA1 nuclei expression in sporadic breast cancers.Loss expression of BRCA1 had significant correlation with higher histological stages,axillary's lymph nodal metastasis(P<0.01),lower expression of ERα,and overexpression of HER-2 protein(P<0.01).Conclusions There are BRCA1 methylations,loss BRCA1 gene copy and loss protein expression in the sporadic breast cancer,the three statues of BRCA1 is correlated to each other;and the loss expression of BRCA1 protein related to part of pathology and clinic parameters.

BRCA-1和TopoII在乳腺癌中的表达及临床病理关系分析

目的研究BRCA-1和TopoII在乳腺浸润性导管癌的表达及临床病理参数的关系,了解两者表达的相关性。方法应用免疫组织化学法检测BRCA-1和TopoII在92例乳腺癌组织的表达。结果乳腺癌组织中BRCA-1表达较癌旁正常乳腺组织明显降低(P<0.05);乳腺癌组织TopoII表达较癌旁正常乳腺组织明显升高(P<0.05);BRCA-1和TopoII在乳腺癌组织中的表达无明显相关性;乳腺癌中肿瘤的大小、组织学分级和淋巴结转移率与BRCA-1的阳性表达呈负相关,与TopoII阳性表达率呈正相关。结论BRCA-1基因表达降低与乳腺癌的发生有密切关系,TopoII是反映细胞恶性程度较客观的指标。

宁夏地区回族女性散发性乳腺癌易感基因BRCA1/BRCA2突变的研究

目的研究宁夏地区回族女性散发性乳腺癌中BRCA1/BRCA2基因(breast cancer susceptibility gene 1/2)的突变位点及携带情况。方法收集60例回族居民乳腺癌石蜡包埋组织标本及15例乳腺小叶增生或纤维腺瘤标本。PCR和DNA直接测序法检测BRCA1基因第2、11和20号外显子和BRCA2基因第11号部分外显子突变情况。结果 60例乳腺癌BRCA1基因有10例突变,突变率为16.7%,突变位点均位于BRCA1基因。15例对照均未检出突变且淋巴结转移与未转移组间BRCA1基因突变率差异(30.8%与5.9%)有统计学意义(P<0.05)。结论 BRCA1基因突变可能与宁夏回族女性乳腺癌发生相关。

NLR、CRP、IL-2、BRCA1、miR-145、miR-21、miR-10b在乳腺癌诊断及预后中的应用

目的探讨中性粒细胞和淋巴细胞绝对值的比值(NLR)、C反应蛋白(CRP)、白介素-2(IL-2)联合乳腺癌易感基因1(BRCA1)、miR-145、miR-21、miR-10b在乳腺癌诊断及预后中的应用价值。方法采用回顾性总结,2016年2月~2018年5月选择在笔者医院诊治的乳腺癌患者60例(癌变组)、良性乳腺肿瘤患者60例(瘤变组组)与健康人60例(对照组),抽取所有患者的静脉血,检测NLR、CRP、IL-2表达水平与BRCA1、miR-145、miR-21、miR-10b阳性表达情况。调查患者的临床特征与随访预后,调查影响预后的因素。结果癌变组的血清CRP、IL-2水平高于瘤变组与对照组,瘤变组高于对照组(P<0.05)。癌变组的NLR值低于瘤变组与对照组,瘤变组低于对照组(P<0.05)。癌变组血液中BRCA1、miR-145、miR-21、miR-10b阳性率高于瘤变组与对照组(P<0.05)。随访至今,癌变组中患者死亡6例,存活54例,病死率为10.0%。癌变组60例患者中,随着淋巴结转移、分化程度减少、病理分期增加与随访死亡,BRCA1、miR-145、miR-21、miR-10b表达阳性率显著增加(P<0.05)。多因素Logistic回归分析淋巴结转移、临床分期、组织学分化、BRCA1、miR-145、miR-21都为影响患者预后死亡的主要独立危险因素(P<0.05)。结论NLR、CRP、白介素-2联合BRCA1、miR-145、miR-21、miR-10b在乳腺癌中呈现异常表达情况,与乳腺癌的病理特征与随访预后显著相关,可应用乳腺癌辅助诊断与预后预测。

BRCA1基因相关的DNA修复通路异常与三阴乳腺癌化疗药物选择的关系

三阴乳腺癌以雌激素受体(estrogen receptor,ER)、孕激素受体(progestogen receptor,PR)以及Her-2阴性为特征,临床表现为组织分化差,术后易出现局部复发和远处转移,而且脏器比骨骼更容易发生转移。因对内分泌治疗和以Her-2为靶向分子的治疗无效,化疗成为治疗方案中的主体。与其他类型乳腺癌比较,三阴乳腺癌患者与乳腺基底细胞样癌和乳癌基因1(BRCA1)相关性乳腺癌在表型和分子生物学水平方面具有很多共性。不同个体DNA损伤修复能力的差异和乳腺癌的发病密切相关。BRCA1以及相关的DNA修复通路中的不同基因,如BRCA2、ATM、RAD51和CHEK2对维护基因组稳定性方面有重要作用。因此,三阴乳腺癌患者BRCA1相关的DNA修复通路异常而导致DNA修复能力异常,影响了其对化疗药物的敏感性,进而可能促进了高转移特性的形成。导致三阴乳腺癌重要脏器转移高发的原因,是肿瘤本身的转移相关基因异常的内因所致,还是对所接受的治疗耐药而使肿瘤细胞处于逃逸状态而引起,目前尚不明确。因此本文对BRCA1相关的DNA修复通路异常与三阴乳腺癌高转移之间的关系进行综述。

BRCA-1基因表达和其它肿瘤标志物在乳腺癌诊断中的应用

目的:探讨BRCA-1基因表达水平在乳腺癌诊断和治疗监测中的应用。方法:采用荧光定量PCR(FQ-PCR)技术检测35例健康女性体检者、40例良性乳腺肿瘤和96例乳腺癌患者外周血中BRCA-1基因表达量,用化学发光法检测其CA153、CA125和CEA,并进行对比分析。结果:BRCA-1对乳腺癌诊断灵敏度显著高于CA153、CA125和CEA。BRCA-1在手术和化疗后显著升高,CA153、CA125和CEA在手术和化疗后均显著下降。结论:BRCA-1基因表达水平可有效监测乳腺癌的诊断、治疗和预后。

BRCA1和BRCA2阴性家族性与散发性乳腺癌患者临床特征及影响新辅助化疗疗效的因素分析

目的分析乳腺癌易感基因1(BRCA1)和乳腺癌易感基因2(BRCA2)阴性家族性与散发性乳腺癌患者的临床特征及影响新辅助化疗疗效的因素。方法回顾性分析393例BRCA1与BRCA2基因突变检测结果为阴性的乳腺癌患者的临床资料,其中家族性乳腺癌54例为A组,散发性乳腺癌339例为B组。通过免疫组化法对两组乳腺癌组织标本中的人表皮生长因子受体2(HER-2)、孕激素受体(PR)及雌激素受体(ER)进行检测。比较两组临床病理特征及化疗后病理完全缓解率的差异,并采用单因素及多因素Logistic回归分析影响新辅助化疗疗效的相关因素。结果 A组患者发病年龄≤30岁、双侧乳腺癌的比率较B组均显著升高(P<0.05);两组患者在病理类型、肿瘤直径、组织学分级、HER-2表达、ER表达、PR表达、淋巴结转移状态和新辅助化疗、三阴性乳腺癌的比率比较,均无显著差异(P>0.05)。经单因素、多因素Logistic回归分析结果均发现,BRCA1、BRCA2阴性乳腺癌患者新辅助化疗的临床疗效与肿瘤直径、组织学分级和是否为家族性乳腺癌、三阴性乳腺癌均存在显著关系(P<0.05)。结论相比BRCA1、BRCA2阴性的散发性乳腺癌患者,BRCA1、BRCA2阴性的家族性乳腺癌患者发病年龄较早,且双侧乳腺癌的占比较高,其在新辅助化疗后的病理完全缓解率较高,因此其有着独特的临床病理特征,患者对新辅助化疗较为敏感。

BRCA1基因启动子甲基化在三阴性乳腺癌中的表达及其临床意义

目的:评估三阴性乳腺癌(TNBC)患者中乳腺癌易感基因1(BRCA1)甲基化的表达及与患者预后的关系。方法:收集在我院甲乳科治疗的乳腺癌患者手术切除标本524例,应用联合亚硫酸氢钠限制性内切酶分析法,观察BRCA1启动子甲基化状态。应用定量逆转录聚合酶链反应评估BRCA1 mRNA表达,应用免疫组织化学法评估BRCA1蛋白表达。结果:共有157(30.0%)例TNBC患者,有25(4.77%)例存在BRCA1启动子甲基化,所有BRCA1启动子甲基化的肿瘤均为TNBC。TNBC患者中,BRCA1启动子甲基化患者的BRCA1 mRNA水平显著低于BRCA1启动子未甲基化患者[(0.019±0.005)vs(0.095±0.013),P<0.001],免疫组化分析未在BRCA1启动子甲基化患者中检测出BRCA1蛋白表达。BRCA1启动子甲基化患者的总生存率(OS)显著低于非甲基化患者(logrank P=0.038)。BRCA1蛋白低表达患者的OS与RFS均低于高表达组,但差异没有统计学意义(分别logrank P=0.526,P=0.467)。结论:BRCA1启动子甲基化导致了BRCA1表达的下降,并与TNBC患者较差预后相关。BRCA1启动子甲基化是一种促成BRCA1功能丧失的重要机制。

非小细胞肺癌患者BRCA1表达与铂类化疗疗效的Meta分析

目的:探讨非小细胞肺癌(NSCLC)患者乳腺癌易感基因1(BRCA1)的表达水平与铂类化疗疗效的相关性。方法:计算机检索中国知网(CNKI)数据库、万方数据库、PubMed、EMBASE和ASCO数据库。纳入的文献均为公开发表的全文文献,所有数据均从原文获得。收集关于接受铂类化疗方案的NSCLC患者BRCA1的表达水平(高表达/阳性与低表达/阴性)与化疗反应率的文章。采用Cochrane协作网RevMan 5.2软件进行Meta分析。结果:最终纳入15项研究,共1273例患者。其中BRCA1高表达/阳性患者720例,铂类化疗有效患者243例,总有效率33.75%。BRCA1低表达/阴性患者553例,铂类化疗有效患者244例,总有效率44.12%。异质性检验结果显示各研究不存在统计学异质性(P=0.03,I2=45%),采用固定效应模型对文献进行综合定量分析,合并OR值为0.63,95%CI为0.50-0.80,Z=4.09,P<0.0001。结论:在NSCLC患者中,BRCA1低表达/阴性者接受铂类化疗的疗效优于BRCA1高表达/阳性者。