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.

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.

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.

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.

Case Report: Complete Clinical Response of a Young Patient with a BRCA 2 Positive Metastatic Breast Cancer

Background: Metastatic breast cancer in BRCA 2 patients is lacking of target therapy studies. Case: We present a case of a 34-year-old woman affected by a recurrent metastatic breast cancer after 5 years treated with weekly nab-paclitaxel and three weekly Cisplatin obtaining a radiological complete response with 6 cycles. Conclusion: It is important to emphasize that patients with a molecular disorder who selected for “target” chemotherapy can obtain optimal response rate. Exploiting the mechanism of action of DNA damage in our favor, using cisplatin for example and basing on literature show the efficacy of using taxane in BRCA 2 patients, obtaining a very high response rate.

Correlation of Kif2a and HPK1 expression in breast cancer with the oncogene and drug resistance gene expression

Objective: To investigate the correlation of Kif2a and HPK1 expression in breast cancer with the oncogene and drug resistance gene expression. Methods: A total of 91 patients with breast cancer and 85 patients with breast adenoma who accepted surgical treatment in our hospital between August 2016 and February 2018 were selected, and the breast cancer tissues and breast adenoma tissues were collected respectively as the research samples. Fluorescence quantitative PCR method was used to detect the expression of Kif2a and HPK1 genes as well as oncogenes and drug resistance genes in sample tissues, and Pearson test was used to evaluate the inner link of Kif2a and HPK1 gene expression in breast cancer tissue with oncogene and drug resistance gene expression. Results: Kif2a mRNA expression in breast cancer tissues was higher than that in breast adenoma tissues whereas HPK1 mRNA expression was lower than that in breast adenoma tissues;oncogenes DEK, iASPP-SV, Stat3, MDM2 and Fra-1 mRNA expression were higher than those in breast adenoma tissues;drug resistance genes ESR1, MDR1, P-gp, MRP1 and GST- mRNA expression were higher than those in breast adenoma tissues whereas BCRP mRNA expression was lower than that in breast adenoma tissues. Correlation analysis showed that the Kif2a and HPK1 gene expression in breast cancer tissues were directly correlated with the expression of oncogenes and drug resistance genes. Conclusion: Kif2a gene is abnormally highly expressed whereas HPK1 gene is abnormally lowly expressed in breast cancer tissues, and they are involved in the regulation of oncogene and drug resistance gene expression.

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。

一步法制备荧光开启传感器检测BRCA2

筛查乳腺癌易感基因2(BRCA2)基因突变对于乳腺癌患病风险评估、发病检测、早期诊断及基因治疗均具有重要临床意义。现有乳腺癌基因传感检测方法大多需要复杂的处理过程,成本较高且对单碱基突变识别能力较弱。为简化基因传感器制备过程,提高其应用可能性,文章通过DNA分子发夹结构设计,一步实现了BRCA2的检测。其中分子发夹茎部含BRCA2互补序列,茎与环连接处标记四甲基罗丹明荧光基团(TAMRA),环部5个G碱基通过光诱导电子转移猝灭部分荧光信号,降低背景荧光信号;待测BRCA2序列与发夹茎部序列竞争结合,发夹结构被打开,荧光信号上升,测量上升的荧光信号强度即可实现一步法定量检测靶基因。优化实验结果表明,分子发夹浓度不同时,传感器检测范围不同。当分子发夹浓度为150 nmol·L^(-1)时,对BRCA2的线性检测区间为1~50 nmol·L^(-1);浓度为300和600 nmol·L^(-1)时,线性检测区间分别为1~100和1~200 nmol·L^(-1)。三种浓度传感器检出限分别为0.54、0.72和1.81 nmol·L^(-1)。此外,传感器对BRCA2的特异性检测较为突出,尤其对单碱基突变的识别能力较强。该方法制备与检测过程简单且特异性突出,不仅可用于乳腺癌高危人群的早期筛查,还可拓展应用于其他种类的基因检测,为基因传感器的推广应用提供一种制备简单、操作便捷的新方法。

HER-2 expression after neoadjuvant chemotherapy of the breast cancers

Objective:The aim of this study was to study changes of HER-2 expression after neoadjuvant chemotherapy in the breast cancer cases.Methods:One hundred and thirty-seven female patients with primary breast cancers,who received neoadjuvant chemotherapy,underwent core needle puncture and Mammotome biopsy before chemotherapy,and the biopsy results were used as the basis of histological diagnosis,fluorescence in situ hybridization (FISH) was performed to test HER2 status of tumor tissues before and after chemotherapy.All patients underwent FEC,TE,or AC neoadjuvant chemotherapy of 2-6 cycles before surgery.Results:Twenty-two patients were positive according to FISH test among 137 preoperative patients,8 patients achieved pathological complete remission after chemotherapy (three HER-2 positive patients and five negative patients),91 patients achieved partial remission,24 patients were stable,and 14 cases were invalid.Twenty-two patients were positive according to FISH test (8 patients with pathological complete remission did not undergo test),and positive patients still expressed positively after chemotherapy before neoadjuvant chemotherapy.Three negative patients were converted to be positive,and changes before and after chemotherapy had no statistical difference (P>0.05).Conclusion:Neoadjuvant chemotherapy makes no influence on patients with HER-2 positive expression,while patients with negative expression can be converted to be positive,but without significant difference.

Accessory breast poorly differentiated adenocarcinoma with positive HER2 gene amplification: A case report

Background: Primary poorly differentiated adenocarcinoma of the accessory breast is rare. We report such a case in a 56-year-old Malaysian woman of Indian ethnicity. Case Presentation: An axillary swelling measuring 5 × 5 cm on excisional biopsy revealed a poorly differentiated adenocarcinoma with positive HER2 gene amplification. Conclusion: Overall prognosis is similar to that of a carcinoma of the normal breast, therefore early diagnosis is imperative to ascertain curable status and improve prognosis.

Construction of recombinant type 5 adenovirus expressing human DBC2 gene in bladder cancer cells

Objective:The aim of the study was to construct recombinant type 5 adenovirus expressing the human DBC2(deleted in breast cancer 2) gene for in vitro and in vivo assay in human bladder cancer research.Methods:The human DBC2 gene was first subcloned into a shuttle plasmid pAdTrack-CMV.After recombining with pAdEasy-1 vector in BJ5183 cells,the new recombinant vector pAdEasy-DBC2-CMV was transfected into HEK-293 cells to produce adenovirus.The human bladder cancer cell line T24 was infected with DBC2-containing adenovirus particles.Both RNA and protein were collected from cells harvested at 72 h after infection.Real time quantitative PCR(qPCR) and Western blot were used to examine mRNA and protein levels.Fluorescence microscopy was utilized to observe the expression of reporter green fluorescence protein.Results:Electrophoresis showed there was a 2.2 kb size band produced from high fidelity PCR.Pac I digest of the final produced recombinant vector yielded band sizes of approximately 30 kb and 4.5 kb.After virus infection with the pAdEasy-DBC2-CMV vector,the T24 cell line was observed to highly express green fluorescence protein under a fluorescence microscope.qPCR and Western blot assay identified that the DBC2 gene was overexpressed at both the mRNA and protein levels in virus transfected cells.Conclusion:By using the pAdEasy adenovirus system,we successfully constructed an adenovirus that could highly overexpress the tumor suppressor DBC2 gene in a bladder cancer cell line.This viral construct would be widely used for our further research in gene functional assays and gene therapy in bladder cancer.

乳腺癌组织lncRNA CASC2、miR-532-3p表达水平与患者术后5年内生存的相关性

目的探究乳腺癌(BC)组织长链非编码RNA癌易感性候选基因2(lncRNA CASC2)、微小RNA-532-3p(miR-532-3p)表达与患者术后5年内生存的相关性。方法选择2015年1月—2018年6月大同市第五人民医院普通外科收治BC患者127例,术中收集BC组织及癌旁正常组织,荧光定量PCR法检测BC组织和癌旁正常组织中lncRNA CASC2、miR-532-3p表达;对BC患者术后进行为期5年的随访,记录患者5年内生存和死亡情况。比较癌旁正常组织和BC组织lncRNA CASC2及miR-532-3p表达,BC组织中lncRNA CASC2和miR-532-3p表达在不同临床病理特征中的差异,生存组和死亡组临床病理特征和BC组织中lncRNA CASC2及miR-532-3p表达的差异。分析BC组织lncRNA CASC2、miR-532-3p表达的相关性;BC组织中lncRNA CASC2和miR-532-3p表达与术后5年内生存的关系;影响BC患者术后5年内生存的因素;lncRNA CASC2、miR-532-3p对BC患者术后5年内生存的预测价值。结果BC组织中lncRNA CASC2表达水平低于癌旁正常组织,miR-532-3p表达水平高于癌旁正常组织(t/P=38.239/<0.001,49.406/<0.001);肿瘤直径≥2 cm、TNM分期Ⅲ期、肿瘤低分化、淋巴结转移者比例lncRNA CASC2低表达组高于高表达组,而miR-532-3p低表达组低于高表达组(lncRNA CASC2:χ^(2)/P=17.361/<0.001、17.052/<0.001、14.694/<0.001、13.173/<0.001;miR-532-3p:χ^(2)/P=10.733/0.001、9.813/0.002、10.134/0.001、7.444/0.006);127例BC患者术后随访5年,生存99例(生存组),死亡28例(死亡组),肿瘤直径≥2 cm、TNM分期Ⅲ期、肿瘤低分化、淋巴结转移者比例及miR-532-3p表达水平死亡组高于生存组,而lncRNA CASC2表达水平死亡组低于生存组[χ^(2)(t)/P=5.211/0.022、27.149/<0.001、27.990/<0.001、4.590/0.032、19.155/<0.001、10.818/<0.001];BC组织中lncRNA CASC2与miR-532-3p表达呈负相关(r/P=-0.561/<0.001);lncRNA CASC2高表达组BC患者术后5年内总生存率为89.23%(58/65),高于lncRNA CASC2低表达组66.13%(41/62)(χ^(2)/P=9.854/0.002);miR-532-3p高表达组BC患者术后5年内总生存率为65.57%(40/61),低于miR-532-3p低表达组89.39%(59/66)(χ^(2)/P=10.466/0.001);肿瘤直径≥2 cm、TNM分期Ⅲ期、肿瘤低分化、有淋巴结转移、lncRNA CASC2低表达、miR-532-3p高表达均是影响BC患者术后5年内生存的独立危险因素[HR(95%CI)=2.255(1.192~4.263)、2.143(1.252~3.666)、3.089(1.386~6.887)、2.219(1.223~4.026)、2.606(1.174~5.788)、2.855(1.592~5.120)];lncRNA CASC2、miR-532-3p及二者联合预测BC患者术后5年内生存的AUC分别为0.840、0.852、0.908,二者联合预测的AUC大于lncRNA CASC2、miR-532-3p各自单独预测的AUC(Z/P=2.246/0.025、2.033/0.042)。结论BC组织中lncRNA CASC2表达下调,miR-532-3p表达上调,且术后5年内死亡的BC患者较存活患者变化更显著,二者表达与临床病理特征相关,对预测BC患者术后5年内生存情况价值较高。

BRCA2在散发性乳腺癌组织中的表达及意义

目的:探讨乳腺癌易感基因2(BRCA2)在散发性乳腺癌组织中的表达及意义,了解BRCA2蛋白的表达与雌激素受体(ER)、孕激素受体(PR)及原癌基因C-erbB-2之间的相关性。方法:采用免疫组化法(SABC)对32例乳腺癌患者癌组织、癌旁组织及正常乳腺组织中BRCA2、C-erbB-2、ER、PR蛋白的表达进行检测并结合年龄、病理组织学分级、腋淋巴结转移情况进行相关性分析。结果:BRCA2在乳腺癌组织中表达的阳性率为56%,而在癌旁及正常乳腺组织中无阳性表达(P<0.05)。BRCA2蛋白的表达在乳腺癌不同组织学分级中有差异(r=0.372 8,P<0.05);与腋下淋巴结转移之间比较差异有显著性(r=0.362 2,P<0.05),但与发病年龄、ER、PR、C-erbB-2表达之间未见相关性。结论:BRCA2蛋白的表达与组织学分级高、腋淋巴结转移相关。BRCA2蛋白的检测有可能成为评估乳腺癌生物学行为和预后的新指标。

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。

乳腺癌患者病理特征与Bcl-2、CXCL13、PAX8表达情况的关系分析

目的分析乳腺癌患者病理特征与B细胞淋巴瘤/白血病-2基因(Bcl-2)、趋化因子配体13(CXCL13)、配对盒基因8抗体(PAX8)表达情况的关系。方法收集2021年1月至2023年1月该院收治的160例乳腺癌患者临床资料。采用免疫组化法对其癌组织与癌旁组织Bcl-2、CXCL13、PAX8表达情况进行检测,并分析3项指标与患者病理特征的关系。结果与癌旁组织比较,癌组织Bcl-2、CXCL13、PAX8阳性率更高,差异有统计学意义(P<0.05)。与雌激素受体(ER)阴性、肿瘤最大径≥3 cm、孕激素受体(PR)阴性患者比较,ER阳性、肿瘤最大径<3 cm、PR阳性患者中Bcl-2高表达占比更高,差异有统计学意义(P<0.05);与无淋巴结转移、Ⅰ~Ⅱ期患者比较,淋巴结转移、Ⅲ~Ⅳ期患者中CXCL13高表达占比更高,差异有统计学意义(P<0.05);与Ⅰ~Ⅱ期、高/中分化、无淋巴结转移患者比较,Ⅲ~Ⅳ期、低分化、有淋巴结转移患者中PAX8高表达占比更高,差异有统计学意义(P<0.05)。ER、PR表达情况与Bcl-2表达情况呈正相关(P<0.05),肿瘤最大径与Bcl-2表达情况呈负相关(P<0.05);临床分期、淋巴结转移情况与CXCL13、PAX8表达情况呈正相关(P<0.05);分化程度与PAX8表达情况呈负相关(P<0.05)。结论乳腺癌患者Bcl-2、CXCL13、PAX8表达情况对疾病的发生和发展具有明显影响,有望成为评估乳腺癌患者病情严重程度的标志物。

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。

中国中部地区乳腺癌遗传易感基因BRCA1/2高通量测序情况分析

目的:分析中国中部女性遗传性乳腺癌患者BRCA1/2基因遗传变异情况,探究中国人群乳腺癌易感基因BRCA1/2的遗传变异热点,为临床乳腺癌风险评估提出可靠依据。方法:对乳甲外科收治的具有乳腺癌家族史的女性患者62例,无家族史正常女性志愿者60例,利用Life Tech Ion Proton高通量测序技术对BRCA1/2基因进行测序分析,并用sanger测序法验证。结果:在62例有家族史乳腺癌患者中,BRCA1基因突变率为25.8%(16/62),BRCA2基因突变率为33.9%(21/62),BRCA1/2有害变异率为11.3%(7/62)。乳腺癌家族史患者组与正常组对比分析,家族史乳腺癌患者组BRCA1/2基因变异率(45.2%)显著高于正常对照组(31.7%)。通过家系分析和数据比对发现BRCA1c.4986+1G>T和BRCA2 5773C>T为中国人群遗传性乳腺癌有害变异。结论:家族遗传性乳腺癌患者BRCA1/2基因变异率显著高于正常人群。通过家系遗传分析并利用高通量测序技术可以有效地筛选出乳腺癌BRCA1/2基因的有害变异,为乳腺癌的风险评估提供可靠的临床依据。

LncRNA CASC2靶向调控miR-155-5p及其对HCC细胞恶性表型的影响

目的:长链非编码RNA(long non-coding RNA,lncRNA)癌易感性候选基因2(cancer susceptibility candidate gene 2,CASC2)在卵巢癌、肝细胞癌(hepatocellular carcinoma,HCC)等多种恶性肿瘤中发挥抑癌基因的作用,但其在HCC中的作用机制尚未完全清楚。本研究旨在分析CASC2在HCC组织中的表达及临床意义,并探讨CASC2对人肝癌细胞系Huh-7细胞恶性表型的影响及其可能的作用机制。方法:采用real-time RT-PCR检测HCC组织和HCC细胞系中CASC2和miR-155-5p的表达水平,分析CASC2的表达水平与HCC患者临床病理特征及预后的关系;采用双荧光素酶报告基因实验检测CASC2和miR-155-5p的靶向关系;将pcDNA3.1-CASC2重组质粒、pcDNA3.1空质粒、miR-155-5p模拟物(mimic)及miR-155-5p模拟物的阴性对照(miR-NC)分别或共同转染至Huh-7细胞中,并根据感染物的不同将细胞分为空白对照组、pcDNA3.1组、pcDNA3.1-CASC2组、pcDNA3.1-CASC2+miR-155-5p组、pcDNA3.1-CASC2+miR-NC组,再分别采用四甲基噻唑蓝(methylthiazolyl tetrazolium,MTT)法、Annexin V/碘化丙啶(propidium iodide,PI)双染色法、Transwell实验检测CASC2靶向调控miR-155-5p对Huh-7细胞增殖、凋亡、迁移及侵袭的影响。结果:CASC2在HCC组织和细胞系中均表达下调,miR-155-5p在HCC组织和细胞系中均表达水平升高,两者呈显著负相关(r=−0.388,P<0.05)。HCC患者中CASC2的表达与甲胎蛋白水平、肿瘤大小、TNM分期、分化程度、肝内转移及不良预后均密切相关(均P<0.05)。CSAC2靶向负调控miR-155-5p的表达,pcDNA3.1-CASC2组细胞增殖活力显著低于空白对照组和pcDNA3.1组(均P<0.05);与pcDNA3.1-CASC2组相比,pcDNA3.1-CASC2+miR-155-5p组细胞的增殖活力增强,差异具有统计学意义(P<0.05)。pcDNA3.1-CASC2组细胞凋亡率明显高于空白对照组和pcDNA3.1组(均P<0.05);与pcDNA3.1-CASC2组相比,pcDNA3.1-CASC2+miR-155-5p组细胞的凋亡率显著降低(P<0.05)。与空白对照组和pcDNA3.1组相比,pcDNA3.1-CASC2组迁移和侵袭细胞数量均显著降低(均P<0.05);与pcDNA3.1-CASC2组相比,pcDNA3.1-CASC2+miR-155-5p组迁移和侵袭的细胞数量均显著升高(均P<0.05)。结论:CASC2在HCC组织和细胞中呈低表达,与HCC预后密切相关,过表达CASC2可通过靶向调控miR-155-5p抑制肝癌细胞的增殖、迁移和侵袭,促进细胞凋亡。

非小细胞肺癌BRCA2的表达及其与ER、PR及c-erbB-2的相关性研究

目的在非小细胞肺癌中检测乳腺癌易感基因(BRCA2)的表达和ER、PR及c-erbB-2蛋白表达特点,探讨BRCA2的表达与ER、PR及c-erbB-2之间的相关性。方法免疫组织化学SP法检测了42例手术切除的非小细胞肺癌中ER、PR、c-erbB-2和BRCA2蛋白表达,根据各种临床病理因素分组进行BRCA2表达阳性率统计学分析。结果BRCA2蛋白表达阳性15例(35.7%);BRCA2蛋白表达阳性率在大于或等于60岁与小于60岁两年龄组间、男女组间、鳞状细胞癌组与腺癌组间及其分化程度以及c-erbB-2表达阳性组与阴性组间比较有显著性差异(P<0.01);而在有无淋巴结转移组间BRCA2蛋白表达阳性率比较无显著性差异(P>0.05);ER、PR在所有非小细胞肺癌病例中均为阴性。结论非小细胞肺癌可见BRCA2和c-erbB-2的表达,其两者的表达具有相关性,可能存在协同作用。提示BRCA2和c-erbB-2可作为反映非小细胞肺癌恶性特征的一个检测指标。