Epigenetic modulation of BRCA-1 and MGMT genes,and histones H4 and H3 are associated with breast tumors

Aberrant patterns in promoter methylation of tumor-suppressor genes and posttranslational modifications of histone proteins are considered as major features of malignancy. In this study, we aimed to investigate promoter methylation of three tumor-suppressor genes (BRCA-1, MGMT, and P16) and three histone marks (H3K9ac, H3K18ac, and H4K20me3) in patients with breast tumors. This case-control study included 27 patients with malignant breast tumors (MBT) and 31 patients with benign breast tumors (BBT). The methylation-specific PCR was used for determining promoter methylation of BRCA-1, MGMT, and P16 genes. Western blot analysis was performed to detect histone lysine acetylation (H3K9ac and H3K18ac) and lysine methylation (H4K20me3). BRCA-1 promoter methylation was detected in 44.4% of the MBT whereas this alteration was found in 9.7% of BBT (P = 0.005). The Kaplan-Meier analysis indicated that hypermethylation in BRCA-1 promoter was significantly associated with poor overall survival of patients with breast cancer (P = 0.039). MGMT promoter methylation was identified in 18.5% of MBT and 0.0% of the BBT (P = 0.01). The frequency of P16 promoter methylation was 25.8% in BBT and 11.1% in MBT (P = 0.12). As compared with BBT, MBT samples displayed the aberrant patterns of histones marks with hypomethylation of H4K20 and hypoacetylation of H3K18 (P = 0.03 and P = 0.04, respectively). There was a negative significant correlation between H3K9ac levels and tumor size in MBT group (r = −0.672; P = 0.008). The present findings suggest that promoter hypermethylation of MGMT and BRCA-1 genes along with alterations in H3K18ac and H4K20me3 levels may have prognostic values in patients with breast cancer. Moreover, the detection of these epigenetic modifications in breast tumors could be helpful in finding new methods for breast cancer therapy.     

Is mammography indicated for women with defective BRCA genes? Implications of recent scientific advances for the diagnosis, treatment, and prevention of hereditary breast cancer

About 5% of breast cancer patients have inherited their disease because of a mutation in genes encoding either the BRCA-1 or BRCA-2 proteins. Inheriting one of these mutations confers a 50% to 87% risk of breast cancer. Many physicians faced with such a patient would, at a minimum, suggest increased and earlier screening for breast cancer by routine mammography.[1] Normally, regular mammographic screening combined with appropriate and prompt treatment can reduce mortality from breast cancer by 30% in women aged 50-59 years and by about 14%-18% in women aged 40-49. There are no controlled clinical trials for screening young women who have multiple first-degree relatives developing breast cancer before age 45, or those known to carry BRCA-1 or BRCA-2 mutations. In fact, recent advances point out that BRCA-1 and BRCA-2 gene products are needed to repair radiation damage to DNA.[4,5] Based on this finding, I propose that women with defective BRCA genes are likely to have an inordinate sensitivity to radiation, and this raises a question about the advisability of routinely screening these women by frequent mammography.     

Clinical significance of blood-based miRNAs as diagnostic and prognostic nucleic acid markers in breast cancer: Comparative to conventional tumor markers

microRNAs (miRNAs) are implicated in carcinogenesis and their expression in biological fluids offer great potential as nucleic acid markers for cancer detection and progression. Authors investigated the expression level of miRNAs (miRNA-21, miRNA-126, and miRNA-155) to evaluate their role as diagnostic and prognostic markers for breast cancer compared with other commonly used protein-based markers (CEA and CA15-3). Serum samples from patients with breast cancer (n = 96), patients with benign breast lesion (n = 47), and healthy individuals (n = 39) were enrolled for detection of miRNA expression levels and protein-based tumor markers using fluorescent real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Correlation among investigated markers with clinicopathological factors and clinical outcomes were determined. Expression of miRNA-21 and miRNA-155 revealed significant increases in patients with breast cancer compared with both benign and control groups, the same result was reported for tumor markers; on the other hand, miRNA-126 was significantly decreased in breast cancer group as compared with the other two groups. miRNA frequencies were significantly related to clinical staging and histological grading as compared with tumor markers. Patients with breast cancer with increased miRNA-21 and miRNA-155 and decreased miRNA-126 expressions had significantly worse disease-free survival, while only miRNA-21 and miRNA-126 showed poor OS (P< 0.005). In conclusion, investigated miRNAs were superior over tumor markers for the early stage of breast cancer especially those with high-risk factor and their assessment in blood facilitates their role as a potential prognostic molecular marker.     

肿块型乳腺癌的超声造影特征及定量参数与sE-cad、sTNFR-P55的相关性及其诊断价值分析

摘要 目的：探讨肿块型乳腺癌的超声造影（CEUS）特征及定量参数与可溶性E-钙黏蛋白（sE-cad）、可溶性肿瘤坏死因子受体P55（sTNFR-P55）相关性研究,并探讨其对肿块型乳腺癌的诊断价值。方法：选取2019年1月至2021年1月于本院诊治并行CEUS检查的162例乳腺肿块患者,根据病理结果分为肿块型乳腺癌组（82例）和良性组（80例）,另选取本院体检健康的80例女性作为对照组。三组均行血清sE-cad、sTNFR-P55水平检测。比较肿块型乳腺癌组与良性组CEUS特征及定量参数的差异,采用Pearson相关分析肿块型乳腺癌患者CEUS定量参数与血清sE-cad、sTNFR-P55水平的相关性。对CEUS、血清sE-cad、sTNFR-P55水平单独或三者联合诊断的方式采用敏感度、特异度、准确性、阳性预测值、阴性预测值指标表达。结果：肿块型乳腺癌组大部分表现为增强后形态不规则、高增强、向心性灌注、造影剂分布不均匀以及呈慢出型的强化方式,且所占比例显著高于良性组（P<0.05）。与良性组相比,肿块型乳腺癌组CEUS定量参数TTP、G显著降低（P<0.05）,而PI、K显著升高（P<0.05）。肿块型乳腺癌组血清sE-cad、sTNFR-P55水平显著高于良性组、对照组（P<0.05）,且良性组血清sE-cad、sTNFR-P55水平还显著高于对照组（P<0.05）。肿块型乳腺癌患者的CEUS定量参数TTP、G与血清sE-cad、sTNFR-P55水平呈负相关（P<0.05）;而PI、k与血清sE-cad、sTNFR-P55水平呈正相关（P<0.05）。CEUS联合血清sE-cad、sTNFR-P55水平诊断肿块型乳腺癌的准确度、敏感度、特异度、阳性预测值、阴性预测值最高。结论：CEUS特征及定量参数对肿块型乳腺癌具有一定的鉴别诊断价值,而且CEUS定量参数与血清sE-cad、sTNFR-P55水平具有一定的相关性,说明CEUS定量参数可在一定程度上可反映乳腺癌的恶性生物学行为;同时CEUS联合血清sE-cad、sTNFR-P55水平检测有助于提高对肿块型乳腺癌的鉴别诊断价值,进一步为临床医生的定性判断提供更加科学的影像学依据。     

DNA methylation in pre-diagnostic serum samples of breast cancer cases: Results of a nested case–control study

Background: Promoter methylation of tumor suppressor genes is a frequent and early event in breast carcinogenesis. Paired tumor tissue and serum samples from women with breast cancer show that promoter methylation is detectable in both sample types, with good concordance. This suggests the potential for these serum markers to be used for breast cancer detection. Methods: The current study was a case–control study nested within the prospective New York University Women's Health Study cohort aimed to assess the ability of promoter methylation in serum to detect pre-clinical disease. Cases were women with blood samples collected within the 6 months preceding breast cancer diagnosis (n = 50). Each case was matched to 2 healthy cancer-free controls and 1 cancer-free control with a history of benign breast disease (BBD). Results: Promoter methylation analysis of four cancer-related genes: — RASSF1A, GSTP1, APC and RARβ2, — was conducted using quantitative methylation-specific PCR. Results showed that the frequency of methylation was lower than expected among cases and higher than expected among controls. Methylation was detected in the promoter region of: RASSF1A in 22.0%, 22.9% and 17.2% of cases, BBD controls and healthy controls respectively; GSTP1 in 4%, 10.4% and 7.1% respectively; APC in 2.0%, 4.4% and 4.2% respectively and RARβ2 in 6.7%, 2.3% and 1.1% respectively. Conclusion: Methylation status of the four genes included in this study was unable to distinguish between cases and either control group. This study highlights some methodological issues to be addressed in planning prospective studies to evaluate methylation markers as diagnostic biomarkers.     

乳腺癌患者血清内IL-6 和CCL-18表达及其与临床病理因素的关系

目的:探究乳腺癌患者血清内白细胞介素-6(IL-6)和趋化因子配体-18(CCL-18)表达水平及其与临床病理因素的关系。方法:本研究于2014年4月~2015年4月期间,选择我院收治31例乳腺癌患者(乳腺癌组)、29例良性肿瘤患者(良性肿瘤组)与30例健康体检者(对照组)为研究对象,采用酶联免疫吸附试验(ELISA)法测定所有研究对象的血清IL-6与CCL-18水平,采用免疫组化法检测患者的临床病理参数。结果:乳腺癌组患者血清IL-6和CCL-18水平均显著高于良性肿瘤组和对照组,良性肿瘤组血清IL-6和CCL-18水平高于对照组,差异均有统计学意义(P0.05);血清IL-6S水平与雌激素受体(ER)、肿瘤增殖抗原(Ki67)、肿瘤TNM分期及淋巴转移存在关联(P0.05),血清CCL-18水平与Ki67与肿瘤TNM分期存在关联(P0.05)。结论:IL-6和CCL-18在乳腺癌患者内出现高表达,且均可预示患者肿瘤的发展恶化,影响预后。     

超声造影联合超声弹性成像组织弥散定量分析在乳腺癌诊断中的应用

摘要 目的：探讨超声造影联合超声弹性成像组织弥散定量分析在乳腺癌诊断中的应用价值。方法：2019年1月至2020年5月选择在本院诊治的乳腺肿瘤患者148例,所有患者都给予超声造影联合超声弹性成像组织弥散定量分析,记录影像学特征。结果：在148例患者中,病理诊断为乳腺癌32例(恶性组),良性乳腺肿瘤116例(良性组)。良性组与恶性组的超声病灶形状、边缘、回声、微钙化等特征对比差异有统计学意义(P<0.05)。恶性组的超声造影增强模式、强度与良性组对比差异都有统计学意义(P<0.05)。恶性组的造影灌注参数曲线下面积(Area under the curve,AUC)、峰值强度(Peak intensity,PI)、上升支斜率(Wash in slope,WIS)值都高于良性组,达峰时间(Time To Peak,TTP)值低于良性组,对比差异都有统计学意义(P<0.05)。恶性组的组织弥散定量参数蓝色区域面积百分比(area ratio,%AREA)低于良性组,标准差(standard deviation,SD)、应变均值(mean,MEAN)值高于良性组,对比差异都有统计学意义(P<0.05)。结论：超声造影联合超声弹性成像组织弥散定量分析在乳腺癌诊断中的应用作为一种经济快捷、实时无创、重复性好的检查方法,能够定量评估乳腺癌的影像学特征,可为乳腺癌的临床治疗提供更多有价值的信息。     

17号染色体不同倍体与乳腺癌临床病理特征的相关性

摘要 目的：探讨17号染色体不同倍体与乳腺癌临床病理特征的相关性。方法：选取2018年1月至2019年12月确诊为乳腺癌的患者78例(乳腺癌组)与乳腺良性肿瘤患者78例(良性组),采用原位荧光杂交检测所有患者的病灶组织染色体不同倍体情况,分析患者的临床病理特征并进行相关性分析。结果：乳腺癌组17号染色体的多倍体率为85.9 %,显著高于良性组(3.8 %,P<0.05)。不同年龄、性别、发病位置、病理类型乳腺癌患者的17号染色体多倍体率对比差异无统计学意义(P>0.05),不同淋巴结转移、组织学分化、临床分期、ER阳性、PR阳性患者的17号染色体多倍体率对比差异具有统计学意义(P<0.05)。Pearson分析显示17号染色体多倍体率与乳腺癌患者的淋巴结转移、组织学分化、临床分期、ER阳性、PR阳性存在显著相关性(P<0.05);多因素Logistic回归分析显示淋巴结转移、组织学分化、临床分期、ER阳性、PR阳性都为17号染色体多倍体的主要危险影响因素(P<0.05)。结论：乳腺癌患者多伴随有17号染色体多倍体,与其患者的淋巴结转移、组织学分化、临床分期、ER阳性、PR阳性等临床病理特征显著相关。     

Network-based approach to identify prognosis-related genes in tamoxifen-treated patients with estrogen receptor-positive breast cancer

Tamoxifen is an estrogen receptor (ER) antagonist that is most commonly used for the treatment of ER-positive breast cancer. However, tamoxifen resistance remains a major cause of cancer recurrence and progression. Here, we aimed to identify hub genes implicated in the progression and prognosis of ER-positive breast cancer following tamoxifen treatment. Microarray data ({"type":"entrez-geo","attrs":{"text":"GSE9893","term_id":"9893"}}GSE9893) for 155 tamoxifen-treated primary ER-positive breast cancer samples were obtained from the Gene Expression Omnibus database. In total, 1706 differentially expressed genes (DEGs), including 859 up-regulated and 847 down-regulated genes, were identified between relapse and relapse-free samples. Weighted correlation network analysis clustered genes into 13 modules, among which the tan and blue modules were the most significantly related to prognosis. From these two modules, we further identified and validated two prognosis-related hub genes (G-rich RNA sequence binding factor 1 (GRSF1) and microtubule-associated protein τ (MAPT)) via survival analysis based on several publicly available datasets. High expression of GRSF1 predicted poor prognosis, whereas MAPT indicated favorable outcomes in ER-positive breast cancer. Using breast cancer cell lines and tissue samples, we confirmed that GRSF1 was significantly up-regulated and MAPT was down-regulated in the tamoxifen-resistant group compared with the tamoxifen-sensitive group. The prognostic value of GRSF1 and MAPT was also verified in 48 tamoxifen-treated ER-positive breast cancer patients in our hospital. Gene set enrichment analysis (GSEA) suggested that GRSF1 was potentially involved in RNA degradation and cell cycle pathways, while MAPT was strongly linked to immune-related signaling pathways. Taken together, our findings established novel prognostic biomarkers to predict tamoxifen sensitivity, which may facilitate individualized management of breast cancer.     

No association between genetic variants in angiogenesis and inflammation pathway genes and breast cancer survival among Chinese women

Background: Angiogenesis and inflammation are implicated in breast cancer prognosis; however, the role of individual germline variation in related genes is unknown. Methods: A two-stage candidate pathway association study was conducted among 6983 Chinese women. Stage 1 included 2884 women followed for a median of 5.7 years; Stage 2 included 4099 women followed for a median of 4.0 years. Cox proportional hazards regression was used to estimate the effects of genetic variants on disease-free survival (DFS) and overall survival (OS). Results: Stage 1 included genotyping of 506 variants in 22 genes; analysis was conducted for 370 common variants. Nominally significant associations with DFS and/or OS were found for 20 loci in ten genes in Stage 1; variants in 19 loci were successfully genotyped and evaluated in Stage 2. In analyses of both study stages combined, nominally significant associations were found for nine variants in seven genes; none of these associations surpassed a significance threshold level corrected for the total number of variants evaluated in this study. Conclusions: No association with survival was found for 370 common variants in 22 angiogenesis and inflammation pathway genes among Chinese women with breast cancer. Impact: Our data do not support a large role for common genetic variation in 22 genes in breast cancer prognosis; research on angiogenesis and inflammation genes should focus on common variation in other genes, rare host variants, or tumor alterations.     

CA19-9及CA72-4联合检测在胰腺癌诊断中的应用价值

目的:探究联合检测血清糖类抗原(CA)19-9和CA72-4水平在胰腺癌诊断中的应用价值。方法:回顾性选取我院2016年1月～2017年12月收治的72例胰腺癌患者作为胰腺癌组,以同期住院的68例良性胰腺病患者作为良性胰腺疾病组,同时纳入67例健康体检者作为对照组。检测三组人群血清CA19-9和CA72-4水平,采用受试者工作特征曲线(ROC曲线)及曲线下面积(AUC)分析评估各单项检测指标及联合检测指标对胰腺癌特异性诊断的价值。结果:胰腺癌组患者血清CA19-9和CA72-4水平分别为(137.69±25.32)U/mL和(6.96±1.25)U/mL,显著高于良性胰腺疾病组和对照组(P0.05)。血清CA19-9和CA72-4联合检测诊断胰腺癌的ROC曲线AUC高于其单独检测(P0.05),CA19-9和CA72-4的最佳临界值分别为86.94 U/m L和4.23 U/m L,此时联合检测诊断胰腺癌的敏感性为94.7%,特异性为95.2%。结论:联合检测血清CA19-9和CA72-4诊断胰腺癌的临床价值明显优于其单独检测。     

Novel markers of gene methylation and expression in breast cancer

An optimized methylation-sensitive restriction fingerprinting technique was used to search for differentially methylated CpG islands in the tumor genome and detected seven genes subject to abnormal epigenetic regulation in breast cancer: SEMA6B, BIN1, VCPIP1, LAMC3, KCNH2, CACNG4, and PSMF1. For each gene, the rate of promoter methylation and changes in expression were estimated in tumor and morphologically intact paired specimens of breast tissue (N = 100). Significant methylation rates of 38, 18, and 8% were found for SEMA6B, BIN1, and LAMC3, respectively. The genes were not methylated in morphologically intact breast tissue. The expression of SEMA6B, BIN1, VCPIP1, LAMC3, KCNH2, CACNG4, and PSMF1 was decreased in 44–94% of tumor specimens by the real-time RT-PCR assay. The most profound changes in SEMA6B and LAMC3 suggest that these genes can be included in biomarker panels for breast cancer diagnosis. Fine methylation mapping of the most frequently methylated CpG islands (SEMA6B, BIN1, and LAMC3) provides a fundamental basis for developing efficient methylation tests for these genes.     

结合素-4（nectin-4）在乳腺癌中表达及其临床意义研究

目的：观察乳腺癌患者血清及乳腺组织中结合素4的表达并探讨其临床意义。方法：选择2007年6月至2008年12月哈尔滨医科大学附属三院收集的40例乳腺癌患者和20例乳腺良性肿瘤患者为研究对象,分为正常对照组、乳腺癌组、乳腺良性肿瘤组,采用Elisa法和免疫组化法对所选择的血清及组织标本中nectin-4及血清中癌胚抗原（CEA）、CA153的表达进行检测。结果：（1）nectin-4的阳性表达定位于细胞质和细胞膜,其在乳腺癌组织中的阳性表达率显著高于乳腺良性组织（P〈0．05）;nectin-4的表达与患者的年龄、临床分期无关（P〉0．05）,但与乳腺癌的病理类型、腋窝淋巴结转移与否、Her-2、ER和PR的表达均显著相关（P〈0．05）。②乳腺癌组血清nectin-4表达水平最高,为238＋4．95pg／ml;乳腺良性病变组为1205：3．28pg／ml;正常对照组为104±5．86pg／ml,三者之间比较,差别有统计学意义（P〈0．01）。③与正常对照组、乳腺良性病变组比较,乳腺癌组血清CEA、CAl53水平均明显升高,差异有显著统计学意义（P〈0．01）。④nectin-4、CEA和CA153诊断乳腺癌的敏感性分别为31．67％、43-33％、28．33％,特异性分别为92．50％、95％、95％,三者联合检测诊断乳腺癌的敏感性较单独检测显著升高（P〈0．05）,可达81．67％。结论：Nectin-4在乳腺癌中高表达,且与乳腺癌的病理类型、腋窝淋巴结转移与否、Her-2、ER和PR的表达均呈显著相关,通过联合检测血清nectin-4、CEA和CA153水平可显著提高乳腺癌诊断的敏感性,有助于乳腺癌的治疗和预后评估,值得临床进一步深入研究。     

彩色多普勒超声应用于乳腺癌诊断及其新辅助化疗疗效评价的临床价值研究

目的:探讨彩色多普勒超声对乳腺良恶性肿瘤的鉴别诊断价值以及其对乳腺癌患者新辅助化疗疗效的评估价值。方法:选取2017年1月到2018年11月期间在我院接受治疗的乳腺癌患者88例作为乳腺癌组,另选取同期在我院接受治疗的乳腺良性肿瘤患者60例作为良性对照组,良性对照组在治疗前,乳腺癌患者在化疗前后采用彩色多普勒超声进行检查,记录所有患者的二维超声表现、彩色多普勒超声表现。结果:乳腺癌组的形态不规则、边界不清晰、内部回声不均匀、后方回声异常的比例均高于良性对照组,差异有统计学意义(P<0.05),两组患者的血流分级分布情况整体比较差异有统计学意义(P<0.05),乳腺癌组的血流阻力指数(RI)高于良性对照组(P<0.05)。化疗后,治疗有效组的乳腺肿瘤体积小于治疗无效组,治疗有效组的形态不规则、边界不清晰、内部回声不均匀、后方回声异常的比例低于治疗无效组(P<0.05),治疗有效组的血流分级分布情况及RI与治疗无效组比较差异亦有统计学意义(P<0.05)。结论:彩色多普勒超声对乳腺良恶性肿瘤具有较高的鉴别诊断价值,同时也可用于乳腺癌患者新辅助化疗疗效的评估。     

Sex hormone-binding globulin selectively modulates estradiol-regulated genes in MCF-7 cells.

Human sex hormone-binding globulin inhibits the effects of estradiol on proliferation and apoptosis of breast cancer cells. We report here the effect of sex hormone-binding globulin on estradiol regulation of gene expression in MCF-7 breast cancer cells using a selected set of genes. Estradiol upregulates genes that are positive regulators of proliferation (e.g., bcl-2, c-fos, c-myc, cyclin D) or/and related to more aggressive form of breast cancer (e.g. BRCA-1, EGF-R) and downregulates two genes (c-jun and ERalpha). Sex hormone-binding globulin modulates only a selected group of estradiol-controlled genes (inhibiting upregulation of bcl-2, c-myc, EGF-R, PR, and downregulation of ERalpha), starting 48 hours after treatment. Our study demonstrates that in breast cancer cells, sex hormone-binding globulin is effective on few selected genes which are involved in cell growth and apoptosis or related to cell estrogen-dependence and that the protein regulation of estradiol effect is selected and specific. Sex hormone-binding globulin action in estrogen breast cancer cells is strongly associated to cell growth and estrogen-sensitivity.     

经直肠剪切波弹性成像技术联合血清CEA、PSA、FPSA对前列腺良恶性病变的鉴别诊断价值研究

摘要 目的：研究经直肠剪切波弹性成像技术（TRSWE）联合血清癌胚抗原（CEA）、前列腺特异性抗原（PSA）、游离前列腺特异性抗原（FPSA）对前列腺良恶性病变的鉴别诊断价值。方法：选取合肥市第二人民医院2019年1月～2022年6月收治的90例前列腺病变患者,根据病理检查分为前列腺癌组（47例）和前列腺良性病变组（43例）。对所有前列腺病变患者均行TRSWE检查,分析前列腺良恶性病变的图像差异以及弹性模量最大值（Emax）、弹性模量平均值（Emean）。检测所有前列腺病变患者的血清CEA、PSA、FPSA水平并进行对比。采用受试者工作特征（ROC）曲线分析明确Emax值、Emean值以及血清CEA、PSA、FPSA水平联合诊断前列腺良恶性病变的效能。结果：前列腺癌组Emax值、Emean值均高于前列腺良性病变组（均P＜0.05）。前列腺癌组血清CEA、PSA及FPSA水平均高于前列腺良性病变组（均P＜0.05）。经ROC曲线分析发现,Emax值、Emean值以及血清CEA、PSA、FPSA水平联合检测诊断前列腺良恶性病变的效能优于上述5项指标单独检测。结论：TRSWE联合血清CEA、PSA、FPSA对前列腺良恶性病变的鉴别诊断价值较高,可有效提升前列腺癌的检出率,可能值得临床推广应用。     

剪切波弹性成像定量参数对乳腺肿块良恶性的鉴别价值及其与组织Ki-67和C-erbB-2表达的关系研究

摘要 目的：探讨剪切波弹性成像（SWE）定量参数对乳腺肿块良恶性的鉴别价值,分析其与组织Ki-67和表皮生长因子受体2（C-erbB-2）表达的关系。方法：选择2021年1月至2022年1月于湖南省妇幼保健院超声医学科行乳腺SWE检查的106例乳腺肿块患者,根据术后或组织活检的病理检查结果分为恶性组59例和良性组47例。对比恶性组和良性组SWE参数的差异以及不同Ki-67和C-erbB-2表达乳腺癌病灶SWE参数的差异。Spearman分析乳腺癌病灶SWE参数与乳腺癌组织Ki-67和C-erbB-2表达的相关性。绘制受试者工作特征（ROC）曲线分析乳腺病灶SWE参数鉴别乳腺肿块良恶性的价值。结果：恶性组AE-max、Shell1 E _max 、Shell2 E _max 、Shell3 E _max 高于良性组（P＜0.05）。联合AE-max、Shell1 E _max 、Shell2 E _max 、Shell3 E _max 鉴别乳腺肿块良恶性的曲线下面积为0.841,高于单独参数鉴别的0.657、0.599、0.642、0.609（P＜0.05）。Ki-67阳性组、C-erbB-2阳性组AE-max、Shell1 E _max 、Shell2 E _max 、Shell3 E _max 高于阴性组（P＜0.05）。乳腺癌病灶AE-max、Shell1 E _max 、Shell2 E _max 、Shell3 E _max 与Ki-67和C-erbB-2表达均呈正相关（P＜0.05）。结论：乳腺恶性肿块与良性肿块的SWE参数存在明显差异,且与乳腺癌组织的Ki-67、C-erbB-2阳性表达有关,乳腺SWE检查有助于鉴别乳腺肿块良恶性。     

超声联合钼靶X线对直径小于1 cm的乳腺癌诊断价值分析

目的:探讨超声联合钼靶X线对直径小于1 cm的乳腺癌诊断价值。方法:选择我院2012年1月至2017年12月收治的66例乳腺疾病患者,所有患者术前均经钼靶X线及彩色多普勒超声检查,分析其病理结果,分析钼靶X线、彩色多普勒超声及二者联合对乳腺肿块的检查结果(边缘毛刺征、血管、淋巴结、微小钙化),比较其对乳腺癌的灵敏度、特异度、准确度、阳性预测值及阴性预测值。结果:66例患者中,经病理检查发现恶性肿瘤34例,良性肿瘤32例。与病理检测相比,彩色多普勒超声联合钼靶X线对乳腺肿块的良恶性检出率无差异性(P0.05),而彩色多普勒超声,钼靶X线的良恶性检出率均显著降低(P0.05)。彩色多普勒超声与钼靶X线良恶性检出率对比无差异(P0.05),但均低于彩色多普勒超声联合钼靶X线的检出率(P0.05)。彩色多普勒超声与钼靶X线对乳腺癌的边缘毛刺征的检出率对比无统计学意义(P0.05);彩色多普勒超声对血管和淋巴结的检出率明显高于钼靶X线,而微小钙化的检出率明显低于钼靶X线,对比差异有统计学意义(P0.05)。彩色多普勒超声联合钼靶X线的灵敏度、特异度、准确度、阳性预测值及阴性预测值均明显高于彩色多普勒超声及钼靶X线(P0.05),钼靶X线及彩色多普勒超声间对比无统计学意义(P0.05)。结论:彩色多普勒超声与钼靶X线对直径小于1 cm乳腺癌的诊断各有优势,二者联合应用的诊断价值优于单一诊断方法。     

Effects of nemorosone,isolated from the plant Clusia rosea,on the cell cycle and gene expression in MCF-7 BUS breast cancer cell lines

Background: Breast cancer is the cause of considerable morbidity and mortality in women. While estrogen receptor antagonists have been widely used in breast cancer treatment, patients have increasingly shown resistance to these agents and the identification of novel targeted therapies is therefore required. Nemorosone is the major constituent of the floral resin from Clusia rosea and belongs to the class of polycyclic polyisoprenylated benzophenones of the acylphloroglucinol group. The cytotoxicity of nemorosone in human cancer cell lines has been reported in recent years and has been related to estrogen receptors in breast cancer cells.Methods: Changes induced by nemorosone in the cell cycle and gene expression of the MCF-7 BUS (estrogen-dependent) breast cancer cell line were analyzed using flow cytometry and the RT² Profiler PCR array, respectively.Results: In comparison to breast cancer cells without treatment, nemorosone induced discrete cell cycle arrest in the G1 phase and significant depletion in the G2 phase. Moreover, the compound altered the expression of 19 genes related to different pathways, especially the cell cycle, apoptosis and hormone receptors.Conclusion: These promising results justify further studies to clarify mechanisms of action of nemorosone, in view of evaluate the possible use of this benzophenone as adjuvant in the treatment of breast cancer.     

A Protein Prioritization Approach Tailored for the FA/BRCA Pathway

Fanconi anemia (FA) is a heterogeneous recessive disorder associated with a markedly elevated risk to develop cancer. To date sixteen FA genes have been identified, three of which predispose heterozygous mutation carriers to breast cancer. The FA proteins work together in a genome maintenance pathway, the so-called FA/BRCA pathway which is important during the S phase of the cell cycle. Since not all FA patients can be linked to (one of) the sixteen known complementation groups, new FA genes remain to be identified. In addition the complex FA network remains to be further unravelled. One of the FA genes, FANCI, has been identified via a combination of bioinformatic techniques exploiting FA protein properties and genetic linkage. The aim of this study was to develop a prioritization approach for proteins of the entire human proteome that potentially interact with the FA/BRCA pathway or are novel candidate FA genes. To this end, we combined the original bioinformatics approach based on the properties of the first thirteen FA proteins identified with publicly available tools for protein-protein interactions, literature mining (Nermal) and a protein function prediction tool (FuncNet). Importantly, the three newest FA proteins FANCO/RAD51C, FANCP/SLX4, and XRCC2 displayed scores in the range of the already known FA proteins. Likewise, a prime candidate FA gene based on next generation sequencing and having a very low score was subsequently disproven by functional studies for the FA phenotype. Furthermore, the approach strongly enriches for GO terms such as DNA repair, response to DNA damage stimulus, and cell cycle-regulated genes. Additionally, overlaying the top 150 with a haploinsufficiency probability score, renders the approach more tailored for identifying breast cancer related genes. This approach may be useful for prioritization of putative novel FA or breast cancer genes from next generation sequencing efforts.