The Role of miRNA-182 and FOXO3 Expression in Breast Cancer

Objective: evaluating the role of FOXO3 mRNA and mi RNA 182-5P expression levels in BC patients. Method: 25 Samples of breast cancer and paired samples of non-cancerous tissues from the same resected breast were obtained from 25 female patients suffering from breast cancer and examined and analyzed by real time PCR to detect the expression levels of FOXO3 mRNA and mi RNA 182-5P. Patients’ data were collected from patients medical records. Results: Foxo3 m RNA expression was down regulated in BC tissues (1.37± 1.96) as compared to control group (23.62 ± 54.39) and decreased FOXO3 expression was associated with larger tumor size (p= 0.046), late histopathological grading (p= 0.002), late TNM staging (<0.001) and increased miR-182 expression (p= 0.025). We found that expression level of miR-182 was significantly higher among breast cancer group (1.10±1.15) as compared to the control group (0.58±0.96 ) with p value = 0.017. We noted a significant increased expression associated with larger tumor size (p= 0.002), late histopathological grading (p= 0.008), late TNM staging (p= 0.002) and decreased FOXO3 expression (p= 0.025). A significant negative correlation between miR-182 and FOXO3 mRNA fold expression with r = - 0.447, and a p value of 0.025, this could be attributed to miRNA targeting FOXO gene. Coclusion: Down regulation of FOXO3 and up regulation of miR-182 expression was associated with advanced breast cancer. The negative correlation between miR-182 and FOXO3 mRNA could be attributed to miRNA targeting FOXO gene.     

Evaluation of miRNA-21 and miRNA Let-7 as Prognostic Markers in Patients With Breast Cancer

Background

Breast cancer remains one of the top threats to women’s health. The current lack of tumor markers with desirable sensitivity and specificity is a major obstacle toward the future management of breast cancer. Many studies are directed to reveal the diagnostic and prognostic potentials of circulating miRNAs in breast cancer. In this study, we attempt to evaluate the feasibility and clinical utility of circulating miRNA-21 and let-7 as prognostic biomarkers for breast cancer.

p-糖蛋白(pgp)在乳腺癌组织中的表达及与预后的关系

目的：研究P－糖蛋白（P－glycoprotein,Pgp)在乳腺癌组织中的表达,评估其在乳腺癌预后中的作用。方法：采用免疫组织化学方法（Immunohistochemistry,IHC)检测47例手术切除的乳腺癌组织中Pgp的表达,并分析其与临床、病理特征的关系及对预的的影响。结果：Pgp在乳腺癌组织中的总表达率为83．0％（39／47例）,高表达者占53．2％（25／47例）,其与月经状、肿瘤大小、淋巴结转移、组织分级和激素受体状况均无关（P＞0．05）;Kaplan-Meier生存分析结果表明Pgp表达与无病生存期和总生存期均显著相关（P＜0．01）,而多因素Cox分析却显著仅有Pgp和淋巴结转移是独立的预后因素,结论：Pgp在乳腺癌组织中具有较高的表达,有可能成为判断乳腺癌预后的有用指标。     

miR-375和PDK1在胰腺癌组织中的表达及两者的相关性

目的探讨miR-375与PDK1在胰腺癌中的表达及两者的相关性。方法qRT-PCR方法检测胰腺癌组织及胰腺癌细胞系中miR-375、PDK1表达,转染miR-375模拟物上调其在Panc-1中的表达,检测转染后Panc-1中PDK1表达变化。结果miR-375在人胰腺癌组织中表达下调,在Panc-1中表达较HEK293明显降低。PDK1在胰腺癌组织中表达上调,在Panc-1中表达较HEK293明显增高。转染miR-375模拟物上调Panc-1中miR-375表达后,转染组PDK1表达较空白组和阴性对照组均明显下降。结论miR-375在胰腺癌中发挥抑癌基因作用,对PDK1具有负调控作用。     

The 70-Gene Prognostic Signature for Korean Breast Cancer Patients

Purpose

A 70-gene prognostic signature has prognostic value in patients with node-negative breast cancer in Europe. This diagnostic test known as "MammaPrint™ (70-gene prognostic signature)" was recently validated and implementation was feasible. Therefore, we assessed the 70-gene prognostic signature in Korean patients with breast cancer. We compared the risk predicted by the 70-gene prognostic signature with commonly used clinicopathological guidelines among Korean patients with breast cancer. We also analyzed the 70-gene prognostic signature and clinicopathological feature of the patients in comparison with a previous validation study.

Methods

Forty-eight eligible patients with breast cancer (clinical T1-2N0M0) were selected from four hospitals in Korea. Fresh tumor samples were analyzed with a customized microarray for the 70-gene prognostic signature. Concordance between the risk predicted by the 70-gene prognostic signature and risk predicted by commonly used clinicopathological guidelines (St. Gallen guidelines, National Institutes of Health [NIH] guideline, and Adjuvant! Online) was evaluated.

Results

Prognosis signatures were assessed in 36 patients. No significant differences were observed in the clinicopathological features of patients compared with previous studies. The 70-gene prognosis signature identified five (13.9%) patients with a low-risk prognosis signature and 31 (86.1%) patients with a high-risk prognosis signature. Clinical risk was concordant with the prognosis signature for 29 patients (80.6%) according to the St. Gallen guidelines; 30 patients (83.4%) according to the NIH guidelines; and 23 patients (63.8%) according to the Adjuvant! Online. Our results were different from previous validation studies in Europe with about a 40% low-risk prognosis and about a 60% high-risk prognosis. The high incidence in the high-risk group was consistent with data in Japan.

Conclusion

The results of 70-gene prognostic signature of Korean patients with breast cancer were somewhat different from those identified in Europe. This difference should be studied as whether there is a gene disparity between Asians and Europeans. Further large-scale studies with a follow-up evaluation are required to assess whether the use of the 70-gene prognostic signature can predict the prognosis of Korean patients with breast cancer.     

MicroRNAs and metastasis-related gene expression in Egyptian breast cancer patients

Aim and background: MicroRNAs (miRNAs) are a class of naturally occurring small noncoding RNAs that regulate gene expression, cell growth, differentiation and apoptosis by targeting mRNAs for translational repression or cleavage. The present study was conducted to study miRNAs in Egyptian breast cancer (BC) and their relation to metastasis, tumor invasion and apoptosis in addition to their association with the ER and PR statuses. Methods: Real Time RT-PCR was performed to identify the miRNA expression level of eight miRNAs and eight metastatic-related genes in 40 breast cancer samples and their adjacent non-neoplastic tissues. The expression levels of each miRNA relative to U6 RNA were determined using the 2–ΔCT method. Also, miRNA expression profiles of the BC and their corresponding ANT were evaluated. Results: The BC patients showed an up-regulation in miRNAs (mir-155, mir-10, mir-21 and mir-373) with an upregulation in MMP2, MMp9 and VEGF genes. We found down regulation in mir-17p, mir-126, mir-335, mir-30b and also TIMP3, TMP1 and PDCD4 genes in the cancer tissue compared to the adjacent non-neoplastic tissues. Mir -10b, mir -21, mir-155 and mir373 and the metastatic genes MMP2, MMP9 and VEGF were significantly associated with an increase in tumor size (P < 0.05). No significant difference was observed between any of the studied miRNAs regarding lymph node metastasis. Mir-21 was significantly over-expressed in ER-/PR- cases. Conclusion: Specific miRNAs (mir-10, mir-21, mir-155, mir-373, mir-30b, mir-126, mir-17p, mir-335) are associated with tumor metastasis and other clinical characteristics for BC, facilitating identification of individuals who are at risk.     

乳腺癌中SPARC基因表达及临床意义

目的探讨乳腺癌组织和血浆中富含半胱氨酸的酸性蛋白(SPARC)的表达在乳腺癌的增殖、侵润和转移中的作用及指导意义。方法采用逆转录聚合酶链反应(RTPCR)分析SPARC在乳腺癌组织和其相邻的正常乳腺组织的差异表达量。采用ELISA法检测正常对照组和乳腺癌患者术前术后血浆中的SPARC水平,探讨SPARC变化的趋势。结果RTPCR分析SPARC在24对配对(48例)乳腺癌组织中的表达,其中17例的表达明显高于其相应的正常乳腺组织,在7例中差异表达不明显,R=70.8%(有差异的例数/总例数)。SPARC基因在不同分化程度的乳腺癌组织中的表达阳性率基本相同(P>0.05)。而在有淋巴结转移的乳腺癌与无淋巴结转移的乳腺癌组织的表达之间的差异有显著意义(P<0.05)。采用ELISA法检测40例正常人和32例乳腺癌患者术前术后血浆SPARC水平。正常人血浆SPARC水平为(644±124)ng/ml。乳腺癌患者术前血浆中的SPARC水平(625±117)ng/ml。正常人和乳腺癌患者术前血浆中的SPARC水平无显著性差异(P>0.05),乳腺癌患者术前比术后血浆中的SPARC水平(611±142)ng/ml略高,但两者无显著性差异(P>0.05)。结论SPARC和乳腺癌的发生与发展密切相关。乳腺癌淋巴结转移时SPARC表达升高。     

淋巴细胞相关炎性反应指标与乳腺癌预后的相关性

目的 探讨治疗前中性粒细胞淋巴细胞比（NLR）、淋巴细胞单核细胞比（LMR）、血小板淋巴细胞比（PLR）与乳腺癌患者临床病理特征及预后的关系。 方法 回顾性分析189例乳腺癌患者的临床资料,应用ROC曲线获得NLR、LMR、PLR的临界值。根据临界值将患者分为高低两组,分析NLR、LMR、PLR与临床病理特征及预后的相关性。结果 NLR、LMR、PLR最佳临界值分别为2.4、5.4、113。高低NLR组患者的新辅助化疗和手术治疗差异有统计学意义（均P<0.05）,高低LMR组和PLR组患者在各临床病理特征方面差异无统计学意义（均P>0.05）。单因素分析结果显示,TNM临床分期、PR表达、NLR、LMR、PLR、手术以及内分泌治疗均与OS有关（均P<0.05）;TNM临床分期、HER2表达、NLR、手术以及内分泌治疗均与PFS有关（均P<0.05）。多因素分析结果显示,TNM临床分期（P=0.003）和NLR（P=0.033）是OS的独立危险因素;TNM临床分期（P=0.002）和手术治疗（P=0.040）是PFS的独立影响因素。结论 治疗前NLR、LMR、PLR与乳腺癌的预后存在显著相关性,但仅NLR是独立危险因素,LMR、PLR尚不能作为独立预测因子。     

抑癌基因PTEN在乳腺癌组织中的表达

目的 探讨10号染色体有缺失且与tensin同源的磷酸酯酶基因（PTEN）在乳腺癌组织中的表达及其意义。方法 采用免疫组织化学S－P法，检测71例乳腺癌组织中PTEN蛋白的表达水平。结果 正常乳腺组织中PTEN呈高表达；有腋淋巴结转移的乳腺癌组织中PTEN高表达率为37．8％，明显低于无腋淋巴结转移者（P＜0．05）；ER阳性者PTEN高表达率明显低于ER阴性者（P＜0．05）；出现远处转移的乳腺癌组织其PTEN高表达率也显著降低（P＜0．01）。PTEN表达水平与患者年龄、肿瘤大小、组织学分级及临床分期无关，但随组织学分级和临床分期的增高，PTEN高表达率呈下降趋势。结论 PTEN表达异常与乳腺癌发生发展密切相关，PTEN低表达的乳腺癌恶性程度高、转移潜能大。     

Combined Expression of Metastasis Related Markers Naa10p,SNCG and PRL-3 and its Prognostic Value in Breast Cancer Patients

Combinations of multiple biomarkers representing distinct aspects of metastasis may have better prognosticvalue for breast cancer patients, especially those in late stages. In this study, we evaluated the protein levels ofN-α-acetyltransferase 10 protein (Naa10p), synuclein-γ (SNCG), and phosphatase of regenerating liver-3 (PRL-3) in 365 patients with breast cancer by immunohistochemistry. Distinct prognostic subgroups of breast cancerwere identified by combination of the three biomarkers. The Naa10p+SNCG-PRL-3- subgroup showed bestprognosis with a median distant metastasis-free survival (DMFS) of 140 months, while the Naa10p-SNCG+PRL-3+subgroup had the worst prognosis with a median DMFS of 60.5 months. Multivariate analysis indicated Naa10p,SNCG, PRL-3, and the TNM classification were all independent prognostic factors for both DMFS and overallsurvival (OS). The three biomarker combination of Naa10p, SNCG and PRL-3 performed better in patients withlymph node metastasis, especially those with more advanced tumors than other subgroups. In conclusion, thecombined expression profile of Naa10p, SNCG and PRL-3, alone or in combination with the TNM classificationsystem, may provide a precise estimate of prognosis of breast cancer patients.     

Expression of the Multidrug-Resistance Gene Product in Untreated Human Breast Cancer and its Relationship to Prognostic Markers

The immunohistochemical expression of the 170-kDa permeability glycoprotein (P-gp) was investigated in 41 primary untreated breast carcinomas, using the monoclonal antibodies C219 and MRK16. DNA ploidy by flow cytometry and estrogen (ER) and progesterone receptor (PgR) contents were also determined. P-gp expression, as revealed by C219 or MRK16, was observed in 6 (14%) of the investigated cancers. P-gp expression had a tendency to occur in non-diploid, high-grade tumors as well as in patients with lymph node negative disease. However, except for lymph node status, these associations were not statistically significant. No positive statistical relationships were observed between other prognostic parameters (age, tumor size, and receptor status) and P-gp expression. Considering the great heterogeneity observed in previous studies and the low expression of P-gp observed hereby, the utility of P-gp immunostaining as a guide for therapy planning in patients with breast cancer remains uncertain.     

雌激素相关标志在乳腺癌中的表达及其预后意义

用一组雌激素相关标志对54例女性乳腺癌进行回顾性研究。患者平均47．9岁，5年生存率为81.5％。癌肿长径平均3．4cm，浸润性导管癌49例，Ⅲ级36例。肿瘤大小、组织学类型、分级与预后关系不明显。ER阳性率55．6％，PR阳性率389％，与组织蛋白酶D有较好相关性。组织蛋白酶D在癌细胞的阳性年为278％，间质巨噬细胞阳性率为100％，与ER、PR关系较密切，并与预后相关。     

新辅助化疗与乳腺癌病理组织形态学及分子水平相关基因的表达

新辅助化疗是指在实施手术或放疗之前应用的全身性化疗,对乳腺癌有良好的近期疗效,同时为化疗药体内药敏试验提供了可靠的依据.以往对新辅助化疗疗效的评定仅限于常规镜下观察化疗后病理形态学改变的组织学评定,结合肿瘤特异性标志物的检测是一种新尝试,从不同层面对新辅助化疗后乳腺癌组织的变化进行观察,客观评价新辅助化疗对指导临床个体化化疗的作用.     

Evaluation of Tumor Markers in Southern Indian Breast Cancer Patients

Tumor markers are biochemical substances elaborated by tumor cells either due to the cause or effect ofmalignant processes. Here we investigated serum levels of cancer antigen (CA15.3) and carcino embryonicantigen (CEA) in 153 pre and post operated southern Indian breast cancer patients (stage-I- 45, stage-II-55,stage-III- 53 samples) and 37 normal controls.Patients with malignant lesions had high frequencies of abnormalCA15.3 in stage-II (46.3%) and stage-III ( 42.6%) and of CEA in stage-III (64.3%). The mean serum levels ofCA 15.3 in all stagesdropped significantly after 9 days of mastectomy, but this was not the case with CEAevenafter 27 days. At 27 days after mastectomy, values for CA 15.3 had again significantly increased. Tumor size,node metastases (≥4) and stage of disease (≥III), but not patient’s age, were associated with higher preoperativelevels. Evaluation of CA15.3 and CEA values showed sensitivities and specificities of 35.3% and 18.3% and95.6% and 62.7%, respectively. Based on these findings we conclude that correlation with CA 15.3 was superiorto CEA in terms of stage of disease, so that this is the more powerful marker for detecting lesions and determiningresponse to treatment.     

Higher Ki67 Expression is Associates With Unfavorable Prognostic Factors and Shorter Survival in Breast Cancer

Background: The prognostic value of the Ki67 expression level is yet unclear in breast cancer. The aim of thisstudy was to investigate the association between Ki67 expression levels and prognostic factors such as grade, Her2and hormone receptor expression status in breast cancers. Materials and Methods: Clinical and pathologicalfeatures of the patients with breast cancer were retreived from the hospital records. Results: In this study, 163patients with breast cancer were analyzed, with a mean age of 53.4±12.2 years. Median Ki67 positivity was 20%and Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001),estrogen receptor (ER) negativity (p=0.035), Her2 positivity (p=0.001), advanced stage (p<0.001) and lymphnode positivity (p<0.003) . Lower Ki67 levels were significantly associated with longer median relapse-free andoverall survival compared to those of higher Ki67 levels. Conclusions: High Ki67 expression is associated withER negativity, Her2 positivity, higher grade and axillary lymph node involvement in breast cancers. The levelof Ki67 expression is a prognostic factor predicting relapse-free and overall survival in breast cancer patients.     

Bone Metastasis in Advanced Breast Cancer: Analysis of Gene Expression Microarray

Background

Approximately 30% to 40% of breast cancer recurrences involve bone metastasis (BM). Certain genes have been linked to BM; however, none have been able to predict bone involvement. In this study, we analyzed gene expression profiles in advanced breast cancer patients to elucidate genes that can be used to predict BM.

乳腺癌组织中c-erbB-2 p53 PCNA及bcl-2蛋白的表达及其临床意义

目的:探讨生物学指标c-erbB-2、p53、PCNA及bcl-2在乳腺癌中的表达与乳腺癌病理生物学行为的关系.方法:应用免疫组织化学方法对56例乳腺癌组织切片c-erbB-2、p53、PCNA及bcl-2的表达进行检测.结果:c-erbB-2表达41.1%,与组织学分级呈正相关,与临床分期、病理类型、患者年龄(≥35岁)、ER、PR受体关系不密切;p53蛋白表达48.2%,与组织学分级、ER、PR受体呈正相关,与患者年龄(≥35岁)、临床分期、病理类型呈负相关;全组PCNA表达100%;bcl-2表达50.0%,与组织学分级、病理类型、ER、PR受体呈负相关,与临床分期呈正相关,与患者年龄(≥35岁)关系不密切.结论:生物学指标c-erbB-2、p53、PCNA及bcl-2应与临床预后因素临床期别、组织学分级等联合应用,提高对乳腺癌预后评价的正确性.