pS2一种新的乳腺癌预后预示因子

ｐＳ２一种新的乳腺癌预后预示因子１韩小红综述２孙素莲审校作者单位：１解放军总医院肿瘤科，北京１００８５３２北京市肿瘤研究所免疫室１０００３４作者简介：韩小红，女，３１岁，硕士，主治医师。研究方向：乳腺癌雌激素受体单克隆抗体的制备及鉴定孙素莲，女，６０...     

ELF5在乳腺癌的表达及意义

目的研究E74-like factor 5 (ELF5)在乳腺癌的表达,探讨ELF5的表达与不同分型乳腺癌预后的关系。方法利用Oncomine数据库挖掘ELF5在乳腺癌组织中的表达;利用Kaplan-Meier Plotter分析ELF5表达水平与雌激素受体阳性/阴性表达乳腺癌生存的关系。结果 Oncomine数据库分析ELF5在乳腺癌中表达降低(P=8.29e~(-10));KM plotter数据库分析结果显示ELF5表达量与雌激素受体阳性表达的乳腺癌无复发生存(RFS)呈正相关,即高表达ELF5的患者无复发生存较高(P=0.008)。结论 ELF5在乳腺癌组织中表达低于癌旁正常组织,其表达水平越高预后越好。     

乳腺癌组织层粘连蛋白受体表达的预后意义

目的：为了观察层粘连层白受体与乳腺癌临床和病理参数之间的关系，以及对患者生存的影响。方法：用免疫组织化学ＬＳＡＢ法检测了１０９例乳腺癌原位灶组织和其中３７例淋巴结转移灶组织中层粘连蛋白受体（ＬＲ）的表达情况，结果：在乳腺癌原发灶中有６０例（５５．０４％）阳性，淋巴结转移灶中３１例（８３．７８％）阳性，两者表达率之间的差异有显著性意义。ＬＲ表达与患者年龄、组织分级、肿瘤坏死和核分裂无显著关系。有淋巴     

细胞周期蛋白E及其与乳腺癌预后关系的研究近况

细胞周期的失控是造成癌细胞恶性增殖及其他特征的主要原因之一 ,而细胞周期蛋白E (CyclinE)在细胞周期中是一种重要的促使细胞进入S期的调节因子 ,它在肿瘤尤其是恶性肿瘤的发生发展过程中起着重要的作用。近年来 ,研究者们认为CyclinE有评估乳腺癌预后的潜力。越来越多的证据表明 ,Cy clinE和其他生物学指标相比 ,它与乳腺肿瘤预后的相关性更大。而CyclinE能否成为较传统的临床病理参数更好的肿瘤分层评估指标尚有待进一步研究。     

P16蛋白在乳腺癌中的表达及其与预后的关系

Ｐ１６蛋白在乳腺癌中的表达及其与预后的关系郭山春廖松林丁华野吴霞孟振行柳剑英皋岚湘田玉旺一、材料和方法９３例乳腺癌标本均为１９８６～１９９５年北京军区总医院外科切除标本，常规取材，１０％福马林固定，石蜡包埋。按１９８２年ＷＨＯ标准进行组织学分型，浸润...     

DKK3蛋白与乳腺癌的临床病理及预后

目的:探讨DKK3 (Dickkopf-3)蛋白在乳腺癌中的表达及其临床意义.方法:采用免疫组织化学方法检测DKK3蛋白在18例乳腺导管内乳头状瘤、14例乳腺非典型增生和103例乳腺癌中的表达,分析其与临床病理特征的关系.结果:在18例乳腺导管内乳头状瘤中,DKK3蛋白的高表达为14例,DKK3蛋白的高表达率为77.8...     

肿瘤标志物在乳腺癌诊断及预后中的应用

肿瘤标志物已广泛应用于乳腺癌的诊断及预后.本综述总结了肿瘤抗原15-3 (CA15-3)、人表皮生长因子受体2( HER2)、雌激素受体(ER)及黄体酮受体(PR)等经典乳腺癌标志物的临床应用现状及新兴乳腺癌生物标志的临床价值.多标志物的联合检测较单一标志物有更高的灵敏度及特异性,将成为今后乳腺癌标志物的临床应用趋势.     

乳腺癌癌基因及相关蛋白与预后的关系

随着人们对乳腺癌认识的深人和诊断、治疗技术的成熟,乳腺癌的存活率逐渐升高,患的生存质量明显改善,但术后局部复发和远处转移的问题仍悬而未决,影响着乳腺癌的预后。近年来,国内外对乳腺癌预后影响因素的研究已从临床病理学及辅助治疗转向分子生物学,本复习了近年来国内外献,着重从乳腺癌癌组织中癌基因及相关蛋白表达角度分析影响乳腺癌预后的相关因素。[第一段]     

乳腺癌原发灶成纤维细胞活化蛋白α表达与患者预后相关

目的本研究旨在探讨乳腺癌原发灶成纤维细胞活化蛋白α(FAP-α)表达与临床病理特征以及预后的关系。方法回顾性收集2000-01-01/2002-12-31期间在解放军总医院手术的130例Ⅰ-Ⅲ期乳腺癌患者的临床资料及石蜡切片,免疫组织化学染色检测乳腺癌原发灶FAP-α表达,分析FAP-α表达与转化生长因子β1(TGF-β1)表达强度的关系,并分析FAP-α表达与乳腺癌预后的关联性以及与临床病理特征的相关性。结果 FAP-α表达在肿瘤细胞和间质成纤维细胞的细胞质,FAP-α阳性纤维细胞密度与TGF-β1阳性间质细胞密度正相关。FAP-α肿瘤细胞质强度与TGF-β1阳性肿瘤细胞质表达正相关。在雌激素受体和孕激素受体均阴性患者中,FAP-α阳性纤维细胞密度是无病生存(DFS)和总生存(OS)的独立不良预后因素;FAP-α阳性肿瘤细胞质强度是DFS和OS的独立不良预后因素。结论激素受体阴性乳腺癌患者中,原发灶FAP-α高表达与不良预后相关。乳腺癌原发灶TGF-β1的表达与FAP-α的表达正相关。     

三阴性乳腺癌患者MutT同源蛋白1基因状态与免疫治疗疗效及预后分析

目的 探讨三阴性乳腺癌（TNBC）患者MutT同源蛋白1(MTH1)基因状态与免疫治疗疗效及预后的关系。方法 选择2017年1月至2019年10月于遂宁市中心医院进行免疫治疗的128例TNBC患者作为研究对象,根据MTH1基因状态分为MTH1突变组（46例）和Non-MTH1突变组（82例）。比较两组患者的临床资料、免疫治疗疗效及预后情况;Kaplan-Meier法绘制生存曲线分析MTH1基因状态与TNBC患者及采用不同方案治疗TNBC患者预后的关系;采用单因素及多因素Cox比例风险回归分析影响TNBC患者预后的因素,构建列线图预测模型并评价其预测效能。结果 MTH1突变组与Non-MTH1突变组患者的肿瘤长径、病理类型、临床分期、脉管或神经浸润、淋巴结转移、治疗方案差异具有统计学意义（P<0.05）;MTH1突变组患者治疗后的客观缓解率和疾病控制率均明显高于Non-MTH1突变组（P<0.05）;采用免疫检查点抑制剂（ICIs）+抗血管生成方案治疗的患者中,MTH1突变组患者的3年无进展生存率及总生存率均明显高于Non-MTH1突变组（P<0.05）;多因素Cox比...     

Overexpression of kin of IRRE-Like protein 1 (KIRREL) as a prognostic biomarker for breast cancer

ObjectivesThe purpose of this study was to investigate the expression of Kin of IRRE-Like Protein 1 (KIRREL) and its clinicopathologic significance in breast cancer.Materials and methodsThe mRNA and protein expressions of KIRREL in fresh breast cancer tissue specimens and the corresponding noncancerous tissue specimens were examined by western blot analysis (n = 24) and RT-qPCR (n = 48). KIRREL was detected by immunohistochemistry (IHC) using breast cancer tissue microarrays (TMAs) in 302 patients. The prognostic roles and clinicopathologic significances in breast cancer were statistically analyzed.ResultsCompared with para-carcinoma tissues, KIRREL mRNA and protein were overexpressed in breast cancer tissues. Immunohistochemical results showed that the high expression rate of KIRREL staining in breast cancer was 43.7% (132/302). Moreover, Expression of KIRREL was significantly correlated with Her2 status and survival outcomes of patients. Patients with both positive expression of KIRREL showed shorter overall survival (OS) and progression free survival (PFS). Additionally, Cox multivariate survival analysis revealed that KIRREL level, age, primary tumor size, tumor stage and distant metastasis were the independent parameter predicting the prognosis of breast cancer patients.ConclusionsKIRREL was overexpressed in breast cancer and the overexpression of KIRREL could serve as an independent predictor of poor prognosis in breast cancer patients.     

ACLY: A biomarker of recurrence in breast cancer

ObjectiveACLY is a cytoplasmic metabolic enzyme involved in lipid synthesis. It also affects proliferation and metastasis of breast cancer. However, the correlation of ACLY expression with breast cancer recurrence is unclear.MethodsThe Oncomine and TCGA databases were used to investigate the mRNA expression of ACLY in breast cancer. Immunohistochemistry (IHC) was used to evaluate ACLY expression level in tumor tissues and normal tissues from 127 breast cancer patients. Next, the prognostic role of ACLY was explored by analyzing the clinicopathological features and prognosis during follow-up. The role of ACLY in breast cancer cells drug resistance was further detected by CCK-8 assays and quantitative real-time polymerase chain reaction (qRT-PCR).ResultsACLY mRNA and protein expression was significantly increased in the breast cancer tissues compared to normal tissues. Clinically, high ACLY levels were associated with ER status, PR status, tumor size, TNM stage, and lymph node invasion. Upregulated ACLY predicted worse tumor relapse-free survival (RFS) of breast cancer patients in univariate analyses and in multivariate models. In subgroup analysis, patients with high ACLY expression showed worse RFS in the TNM III or ER positive subgroups. Moreover, ACLY over-expression induced the resistance of breast cancer cells to docetaxel and promoted the expression of multi-drug resistant protein ABCB1/ABCG2.ConclusionsOur study highlights the possibility of ACLY as a potential and independent biomarker for the recurrence prediction in breast cancer patients. It may be related to ACLY promoting drug resistance in breast cancer cells.     

Both high expression of pyruvate kinase M2 and vascular endothelial growth factor-C predicts poorer prognosis in human breast cancer

Pyruvate kinase M2 (PKM2) and vascular endothelial growth factor-C (VEGF-C) have been known to play an important role in tumorigenesis and tumor progression in breast cancer. However, the association between PKM2 and VEGF-C in breast cancer remains unclear. In the present study, a total of 218 specimens from breast cancer patients and 26 paired breast tumors with adjacent normal tissues as well as two breast cancer cell lines were enrolled to investigate the correlation between PKM2 and VEGF-C. We found that PKM2 and VEGF-C mRNA levels were both significantly increasing in breast tumors compared with adjacent normal tissues. Knockdown of PKM2 mRNA expression resulted in VEGF-C mRNA and protein down-regulated as well as cell proliferation inhibited. A positive correlation between PKM2 and VEGF-C expression was identified by immunohistochemical analyses of 218 specimens of patients with breast cancer (P=0.023). PKM2 high expression was significantly correlated with histological grade (P=0.030), lymph node stage (P=0.001), besides VEGF-C high expression was significantly associated with lymphovascular invasion (P=0.012). While combined high expression of PKM2 and VEGF-C was found to be associated with worse histological grade, more lymph node metastasis, more lymphovascular invasion, shorter progression free survival (PFS), and poorer overall survival (OS) in human breast cancer. The results of the present study suggested that PKM2 expression was correlated with VEGF-C expression, and combination of PKM2 and VEGF-C levels had the better prognostic significance in predicting the poor outcome of patients with breast cancer.     

ACTL8的表达与乳腺癌临床病理特征及预后的关系

目的:探讨肌动蛋白样蛋白8(ACTL8)在乳腺癌中的表达及其与乳腺癌临床病理特征及预后的关系。方法:采用Western blot方法检测人正常乳腺上皮细胞株MCF-10A和5种乳腺癌细胞株中ACTL8蛋白的表达;采用免疫组织化学方法检测6例乳腺癌标本及其对应的癌旁组织中ACTL8蛋白的表达;收集TCGA乳腺癌数据集,将488例乳腺标本纳入,分析ACTL8的mRNA表达水平与乳腺癌患者临床病理特征及预后的关系。结果:ACTL8蛋白在乳腺癌细胞株T47D、BT474、HCC1954和SKBR3中表达显著高于乳腺上皮细胞株MCF-10A;ACTL8蛋白在乳腺癌组织中的表达也显著高于癌旁组织;ACTL8 mRNA表达与乳腺癌患者年龄、肿瘤大小、临床TNM分期和淋巴结转移相关(P0.05)。ACTL8 mRNA高表达的乳腺癌患者5年内生存率低、预后差。结论:ACTL8在乳腺癌组织中高表达并与乳腺癌临床病理特征及预后密切相关,提示ACTL8可作为判断乳腺癌预后的标志物。     

乳腺癌中跨膜蛋白81基因高表达不利于患者预后

目的　揭示乳腺癌组织中跨膜蛋白81（TMEM81）的表达变化及其与预后的关系。 方法　使用TCGA数据库的门户网站cBioPortal、UALCAN以及癌症多组学和临床数据库LinkedOmics分析TMEM81在乳腺癌组织中的变化及其与临床预后的关系。 结果　cBioPortal分析结果显示26%乳腺癌患者癌组织中TMEM81基因发生了改变,包括突变、拷贝数畸变和mRNA水平上调, mRNA水平上调超过默认阈值（EXP≥2）的比例为18%,且TMEM81 mRNA水平上调不利于患者预后（P<0.05）;UALCAN分析结果显示乳腺癌组织中TMEM81 mRNA水平显著高于正常组织（P<0.01）;LinkedOmics分析结果显示癌组织TMEM81 mRNA水平分别受到乳腺癌PAM50分型、雌激素受体、孕激素受体、病理分期、病理T分期、组织学类型、种族和年龄的影响（P<0.01, P<0.01,P<0.01,P<0.01,P<0.01,P<0.01,P<0.01,P<0.05）。最后, TMEM81 mRNA水平与其基因拷贝数畸变正相关（P<0.01）,而与其DNA甲基化水平负相关（P<0.01）。 结论　乳腺癌组织中TMEM81基因拷贝数增加和甲基化水平降低促进其表达,TMEM81高表达不利于预后,可作为乳腺癌预后的候选标志物。     

Association of ABCB1 and VEGFA gene polymorphisms with breast cancer susceptibility and prognosis

Breast cancer (BC) is the most common cause of cancer-related death in women worldwide. Several ABCB1 and VEGFA gene polymorphisms, such as ABCB1-G1199 T/A (rs2229109), VEGFA -634 G > C (rs2010963), VEGFA 2578 C > A (rs699947) and VEGFA 7 C > T (rs25648) have been associated with risk of BC and clinical outcomes. The purpose of this study was to evaluate the association between these gene polymorphisms and BC risk and prognosis.A retrospective case-control study was conducted, including 84 BC cases and 119 controls of Spanish (European, Caucasian) origin. ABCB1-G1199 T/A (rs2229109), VEGFA -634 G > C (rs2010963), VEGFA 2578 C > A (rs699947) and VEGFA 7 C > T (rs25648) gene polymorphisms were analysed by TaqMan®.The genotypic logistic regression model adjusted by aged revealed no association with any of the polymorphisms and BC risk, although the C-allele of VEGFA 2578 C > A showed a trend to higher BC risk in the allelic and recessive models (p = 0.055 and 0.054, respectively). There was no influence of these gene polymorphisms on overall survival (OS). The univariate Cox model showed that carriers of the A-allele for VEGFA 2578 C > A tended to have longer OS compared to CC patients (CC vs A-allele Hazard ratio (HR): 2.08; CI95 % = 0.96–4.49; p = 0.0587). There was no association between the gene polymorphisms analysed and disease-free survival (DFS). The univariate Cox model showed a trend toward a longer DFS in patients carrying ABCB1-G1199 T/A GG genotype compared to those with A-allele (GG vs A-allele HR: 0.43; CI95 % = 0.18–1.03; p = 0.0612).No influence of ABCB1-G1199 T/A (rs2229109), VEGFA -634 G > C (rs2010963), VEGFA 2578 C > A (rs699947) and VEGFA 7 C > T (rs25648) gene polymorphisms on risk of developing BC was found in our study. There was no association between the polymorphisms studied and DFS and OS.     

Significant association of PKM2 and NQO1 proteins with poor prognosis in breast cancer

Pyruvate kinase M2 (PKM2) and NAD(P)H:quinone oxidoreductase-1 (NQO1) have been known to play significant functions in tumorigenesis and development. The association between PKM2 and NQO1 in breast cancer continues, however, to be unclear. In the present study, according to UALCAN and GEPIA database, the mRNA levels of PKM2 and NQO1 in breast primary tumor were significantly higher compared to normal breast tissue. Consonant with these findings, increased expression of both PKM2 and NQO1 were detected in clinical samples and BC cell lines. More importantly, consolidated high expression of NQO1 and PKM2 were obtained to be related with worse clinical stage, relapse, shorter relapse free survival (RFS), and poorer overall survival (OS) in human breast cancer. We subsequently found that knockdown of NQO1 reduced the protein level of PKM2 significantly. Moreover, deletion of PKM2 significantly reduced colony formation, migration and invasion of BC cells. A positive correlation between PKM2 and NQO1 expression was identified by immunohistochemical analyses of 108 specimens of breast cancer patients (rs = 0.60, P = 0.00). Finally, endogenous Co-IP demonstrated that PKM2 and NQO1 interact in breast cancer cells. The results of this study suggest that the correlation between NQO1 and PKM2 might play a critical role during breast tumourigenesis and serve as novel diagnostic biomarkers for breast cancer.     

ALEX1 may be a novel biomarker for human cervical squamous cell carcinoma

The armadillo repeat proteins were first found in armadillo gene of Drosophila. Since then a number of proteins containing armadillo repeats have been noticed and studied. These proteins that consist of 6 to 13 armadillo repeat domains are classified as family of armadillo repeat proteins. Recently, several studies indicated that armadillo repeat family of proteins play an important role in the tumorigenesis and maintenance of tissue integrity. ALEX1 (Arm protein lost in epithelial cancers, on chromosome X), contains two armadillo repeats domains, is expressed different in normal and carcinomas tissues. Several studies have found that ALEX1 protein lost in tumors that originated in epithelial tissues. We evaluated the ALEX1 protein expression in 53 cervical cancers and in 53 non-cancerous cervical tissues from patients and adjacent non-cancerous tissues using immunohistochemistry Results: ALEX1 protein expression is significantly increased in 53 cervical cancers tissues compared with non-cancerous tissues. We found, for the first time, that ALEX1 protein expression in cervical cancers tissues is higher than non-cancerous tissues. It is suggested that the ALEX1 protein is associated with tumorigenesis in cervical cancer and we speculate that the ALEX1 may plays a role as an oncogene in cervical cancer. Moreover, ALEX1 may serve as a novel potential diagnostic biomarker in identifying cervical cancer.     

乳腺癌肿瘤出芽与肿瘤浸润淋巴细胞及患者预后的关系研究

目的:研究肿瘤出芽与乳腺癌临床病理特征、肿瘤浸润淋巴细胞(TILs)以及患者预后的关系。方法:收集2012年1月～2016年12月于暨南大学附属第一医院行手术治疗的178例乳腺癌患者资料及肿瘤组织切片,显微镜下观察乳腺癌组织病理切片中肿瘤出芽和肿瘤浸润淋巴细胞水平,X~2检验分析肿瘤出芽水平与乳腺癌患者临床病理特征和TILs的关系,Log-rank检验分析肿瘤出芽水平与乳腺癌患者无病生存期和总生存期的关系。结果:高肿瘤出芽组患者淋巴结阳性数目多、组织性分级高、脉管癌栓更多;肿瘤出芽数较多的患者TILs的水平较低,而肿瘤出芽数较少的患者TILs水平较高;高肿瘤出芽患者比低肿瘤出芽患者预后较差。结论:乳腺癌肿瘤出芽水平与恶性程度高的临床病理指标密切相关,肿瘤出芽水平与TILs水平呈负相关,是影响乳腺癌预后的重要因素。