Identification and validation of a new prognostic signature based on cancer-associated fibroblast-driven genes in breast cancer

BACKGROUND Breast cancer(BC),a leading malignant disease,affects women all over the world.Cancer associated fibroblasts(CAFs)stimulate epithelial-mesenchymal transition,and induce chemoresistance and immunosuppression.AIM To establish a CAFs-associated prognostic signature to improve BC patient out-come estimation.METHODS We retrieved the transcript profile and clinical data of 1072 BC samples from The Cancer Genome Atlas(TCGA)databases,and 3661 BC samples from the The Gene Expression Omnibus.CAFs and immune cell infiltrations were quantified using CIBERSORT algorithm.CAF-associated gene identification was done by weighted gene co-expression network analysis.A CAF risk signature was established via univariate,least absolute shrinkage and selection operator regression,and mul-tivariate Cox regression analyses.The receiver operating characteristic(ROC)and Kaplan-Meier curves were employed to evaluate the predictability of the model.Subsequently,a nomogram was developed with the risk score and patient clinical signature.Using Spearman's correlations analysis,the relationship between CAF risk score and gene set enrichment scores were examined.Patient samples were collected to validate gene expression by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS Employing an 8-gene(IL18,MYD88,GLIPR1,TNN,BHLHE41,DNAJB5,FKBP14,and XG)signature,we attemp-ted to estimate BC patient prognosis.Based on our analysis,high-risk patients exhibited worse outcomes than low-risk patients.Multivariate analysis revealed the risk score as an independent indicator of BC patient prognosis.ROC analysis exhibited satisfactory nomogram predictability.The area under the curve showed 0.805 at 3 years,and 0.801 at 5 years in the TCGA cohort.We also demonstrated that a reduced CAF risk score was strongly associated with enhanced chemotherapeutic outcomes.CAF risk score was significantly correlated with most hallmark gene sets.Finally,the prognostic signature were further validated by qRT-PCR.CONCLUSION We introduced a newly-discovered CAFs-associated gene signature,which can be employed to estimate BC patient outcomes conveniently and accurately.

Association of survivin splice variants with prognosis and treatment of breast cancer

The purpose of this study was the overview of current knowledge regarding the use of survivin and its isoforms in prognosis and treatment of breast cancer. An advanced search of Medline was performed using the following search strategy: "(survivin isoforms) OR(survivin transcript variants) AND(breast cancer) AND(neoplasm OR tumor OR cancer OR carcinoma)". Relevant studies were retrieved and processed thoroughly in order to analyze the related data. Besides wild-type survivin full-length transcript, another six splice variants have been identified. Overexpression of survivin and its isoforms leads to shorter overall and disease-free survival; the transcript variants are correlated with apoptosis and could assist prognosis prediction. It has been proved through numerous studies that inhibiting survivin isoforms might become a promising target of drug therapy of carcinomas. Use of small molecule YM155 could offer new therapy for triple negative breast cancer patients, while, chemotherapy with 5-fluorouracil + epirubicin + cyclophosphamide and Tax-Epi could be guided by survivin splice variants measurements. Survivin transcript variants could become prognostic biomarkers and could provide information about clinical managementof patients suffering from breast cancer.

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.

iCEMIGE: Integration of CEll-morphometrics, MIcrobiome, and GEne biomarker signatures for risk stratification in breast cancers

BACKGROUND The development of precision medicine is essential for personalized treatment and improved clinical outcome,whereas biomarkers are critical for the success of precision therapies.AIM To investigate whether iCEMIGE(integration of CEll-morphometrics,MIcro-biome,and GEne biomarker signatures)improves risk stratification of breast cancer(BC)patients.METHODS We used our recently developed machine learning technique to identify cellular morphometric biomarkers(CMBs)from the whole histological slide images in The Cancer Genome Atlas(TCGA)breast cancer(TCGA-BRCA)cohort.Multivariate Cox regression was used to assess whether cell-morphometrics prognosis score(CMPS)and our previously reported 12-gene expression prognosis score(GEPS)and 15-microbe abundance prognosis score(MAPS)were independent prognostic factors.iCEMIGE was built upon the sparse representation learning technique.The iCEMIGE scoring model performance was measured by the area under the receiver operating characteristic curve compared to CMPS,GEPS,or MAPS alone.Nomogram models were created to predict overall survival(OS)and progress-free survival(PFS)rates at 5-and 10-year in the TCGA-BRCA cohort.RESULTS We identified 39 CMBs that were used to create a CMPS system in BCs.CMPS,GEPS,and MAPS were found to be significantly independently associated with OS.We then established an iCEMIGE scoring system for risk stratification of BC patients.The iGEMIGE score has a significant prognostic value for OS and PFS independent of clinical factors(age,stage,and estrogen and progesterone receptor status)and PAM50-based molecular subtype.Importantly,the iCEMIGE score significantly increased the power to predict OS and PFS compared to CMPS,GEPS,or MAPS alone.CONCLUSION Our study demonstrates a novel and generic artificial intelligence framework for multimodal data integration toward improving prognosis risk stratification of BC patients,which can be extended to other types of cancer.

Bioinformatics analysis of key genes associated with the prognosis of breast cancer

Objective:We sought to identify potential therapeutic targets for breast cancer patients by employing a bioinformatics analysis to screen for genes linked with an unfavorable prognosis.Methods:The Gene Expression Omnibus(GEO)database was utilized to obtain three gene expression profile datasets,namely GSE42568,GSE86374,and GSE71053.To identify differentially expressed genes(DEGs),the GEO2R online tool was employed.Subsequently,a func-tional enrichment analysis was conducted.Moreover,a protein-protein interaction network was established using STRING,and DEGs were subjected to module analysis via Cytoscape software to identify pivotal genes.Additionally,the selected pivotal genes underwent further ex-amination and validation utilizing three databases:GEPIA,UALCAN,and Kaplan-Meier Plotter.Results:A total of 121 DEGs were detected,comprising 74 genes with increased expression and 47 genes with decreased expression.Ten key genes were identified:HMMR,RRM2,CDK1,TOP2A,AURKA,CCNB1,MAD2L1,KIF2C,BUB1B,UBE2C.Validation in the GEPIA database revealed high expression levels for all key genes except CDK1.A survival analysis conducted using the Kaplan-Meier Plotter database revealed noteworthy associations between nine crucial genes and the overall survival(OS)of individuals diagnosed with breast cancer.Moreover,these nine key genes exhibited significantly increased expression across different molecular subtypes of breast cancer according to the UALCAN data platform.Conclusions:We identified nine crucial genes significantly linked to the onset,progression,and unfavorable prognosis of breast cancer,providing potential targets for novel treatment options and biomarkers to predict patient outcomes.

CLINICOPATHOLOGICAL SIGNIFICANCE OF PTEN AND CASPASE-3 EXPRESSIONS IN BREAST CANCER

Objective To investigate the expressions of PTEN and Caspase-3 proteins in human breast carcinoma,and to evaluate their clinicopathological implications during the tumorigenesis and progression of breast cancer.Methods The expressions of PTEN and Caspase-3 proteins in 95 cases of breast cancer and 15 cases of benign breast diseases were investigated immunohistochemically.Correlations between the expression of PTEN protein,Caspase-3 protein,and clinicopathological features of breast cancers were analyzed.Results The loss expression rate of PTEN protein in tumor tissues was significantly higher than that in benign breast diseases(33.7% vs.0,P<0.01).Analysis of the clinicopathological features showed that PTEN expression level was negatively correlated with TNM stage,histological grade,axillary lymph node status,recurrence,and metastasis(P<0.05).The positive expression level of Caspase-3 was negatively correlated with TNM stage(P<0.01),but not related with histological grade,axillary lymph node status,recurrence,or metastasis(P>0.05).In addition,the expression of PTEN protein had significantly positive correlation with the expression of Caspase-3 protein in breast cancer(P<0.01).Conclusion The combination detection of PTEN and Caspase-3 may serve as an important index to estimate the pathobiological behavior and prognosis of breast cancer.

三阴性乳腺癌组织中EGR1、AR、H3K4me3表达与其临床病理特征及预后的相关性

目的探讨三阴性乳腺癌组织中早期生长反应基因1(EGR1)、雄激素受体(AR)、组蛋白H3第4位赖氨酸三甲基化(H3K4me3)表达与其临床病理特征及预后的相关性。方法回顾性分析89例三阴性乳腺癌患者的临床资料,所有患者均行手术治疗,采用免疫组化染色法测定EGR1、AR、H3K4me3表达,比较肿瘤组织及癌旁正常组织内EGR1、AR、H3K4me3表达差异,分析EGR1、AR、H3K4me3表达与其临床病理的关系,分析EGR1、AR、H3K4me3表达与其预后的关系。结果肿瘤组织内EGR1阳性表达率、AR阳性表达率低于对照组,H3K4me3阳性表达率高于对照组,差异有统计学意义(P<0.05);EGR1阳性表达、AR阳性表达患者临床分期Ⅰ~Ⅱ期、无淋巴结转移、中高分化占比高于EGR1阴性表达、AR阴性表达患者,H3K4me3阳性表达患者临床分期Ⅲ期、淋巴结转移、低分化占比高于H3K4me3阴性表达患者,差异有统计学意义(P<0.05);随访1年,89例患者共36例出现复发转移,发生率为40.45%(36/89);复发转移组EGR1阳性表达、AR阳性表达率低于未复发转移组,H3K4me3阳性表达率高于未复发转移组,差异有统计学意义(P<0.05)。结论EGR1、AR在三阴性乳腺癌中多呈阴性表达,H3K4me3则以阳性表达为主,三者表达均与临床分期、淋巴结转移及分化程度存在密切关系,或可作为临床治疗的新靶点。

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。

基于TCGA数据库筛选与三阴型乳腺癌预后相关的miRNAs及其基因网络

目的:筛选与三阴型乳腺癌(TNBC)预后相关的关键微小RNA(miRNAs)及其靶基因,探讨其参与调控的生物学功能和信号通路,为TNBC患者预后标志物的筛选提供理论依据。方法:基于癌症基因组图谱(TCGA)数据库筛选TNBC患者与非TNBC患者差异表达miRNAs,通过生存分析明确与患者预后相关的miRNAs。利用miRDB和miRWalk3.0在线数据库筛选miRNAs的靶基因,Cytoscape 3.8.2软件明确miRNA-信使核糖核酸(mRNA)调控网络,利用R软件limma数据包筛选TNBC患者与非TNBC患者差异表达miRNAs,利用R软件clusterProfiler包分析靶基因参与的生物学功能和通路。结果:生存分析,miR-9、miR-17、miR-31、miR-146a、miR-188和miR-190b与TNBC患者的预后有关,且上述miRNAs表达量越低,TNBC患者预后越差。筛选出受这6种miRNAs调控的靶基因224个。基因本体论(GO)功能富集分析,靶基因主要参与乳腺腺泡的发育、DNA转录的正向调控以及血管生成等功能;京都基因与基因组百科全书(KEGG)信号通路富集分析,靶基因主要富集在细胞因子-细胞因子受体相互作用以及胰岛素分泌信号等通路。网络分析,miR-9、miR-17、溶质载体家族24成员2(SLC24A2)、vav鸟苷酸交换因子3(VAV3)、三部结构域含有36(TRIM36)、突触标记素1(SYT1)、富勒林和Sec7结构域含有3(PSD3)、过氧化物酶体增殖物活化受体α(PPARA)、RNA聚合酶Ⅲ亚基G(POLR3G)、多形性腺瘤基因1(PLAG1)、泛素相关和SH3结构域含有B(UBASH3B)及SH3结构域和四重肽重复2(SH3TC2)是调控网络中的关键基因,其中miR-9-SYT1、miR-9-KIF13B、miR-9-KITLG、miR-17-SLC24A2、miR-31-SLC24A2、miR-146a-SYT1、miR-146a-KIF13B、miR-188-SLC24A2和miR-188-SLC24A2的miRNA-mRNA相互作用最为密切。结论:miR-9、miR-17、miR-31、miR-146a、miR-188和miR-190b及其靶基因参与乳腺腺泡发育和血管生成等生理过程,与TNBC患者的不良预后密切相关。

基于TCGA数据筛选乳腺癌预后相关的tsRNA标志物

目的筛选乳腺癌中差异表达的转运RNA衍生小RNA(tsRNA),构建与乳腺癌患者预后相关的预测模型。方法收集癌症基因组图谱(TCGA)数据库中的乳腺癌患者的tsRNA表达谱以及临床相关数据,利用最小绝对值收敛和选择算子算法(LASSO)筛选出关键tsRNA,构建风险评分模型和列线图预测模型。结果从乳腺癌差异表达的106条tsRNA中识别了11条非零系数的tsRNA,据此构建了评估乳腺癌预后的风险评分模型和列线图预测模型,经测试集和校准曲线证实两模型均具有良好的预测能力。进一步预测上述11条tsRNA的靶基因,发现其富集了8条KEGG通路,包括多条与肿瘤的进展相关的通路;经相关性分析发现,NR2C2和ZNFX1与tRF-21-YBOZZ7ND的表达水平呈负相关。结论成功构建了风险评分模型和列线图预测模型,有望为乳腺癌的预后评估提供新的方法。

HSP-90α在乳腺癌中的诊断价值及功能富集分析

目的探讨血浆HSP-90α水平对乳腺癌的诊断价值及其编码基因HSP90AA1在乳腺癌防治中的作用。方法采用酶联免疫法检测120例乳腺癌患者(乳腺癌组)和84例乳腺良性肿瘤患者(对照组)血浆HSP-90α含量,利用最佳截断值将患者分为HSP-90α表达阳性组和阴性组,分析HSP-90α表达水平与乳腺癌临床病理特征的关系。采用TCGA数据库分析HSP90AA1基因在乳腺癌及正常乳腺组织中的差异表达和对乳腺癌患者预后的影响;采用LinkedOmics进行基因集富集分析。利用TISIDB分析HSP90AA1基因表达与免疫细胞浸润的关系。结果乳腺癌组血浆HSP-90α较对照组显著升高(P<0.0001);血浆HSP-90α含量80.84 ng·mL-1作为乳腺良、恶性肿瘤的截断值,其诊断灵敏度和特异度分为65.83%和77.38%(AUC:0.77;95%CI:0.71~0.83,P<0.01)。HSP-90表达阳性组患者(n=79)较阴性组(n=41)病理分级及高Ki-67指数更高(P<0.05)。HSP90AA1基因在乳腺癌组织中高表达,且HSP90AA1高表达的乳腺癌患者预后更差(P<0.001)。功能分析表明HSP90AA1基因与RNA运输、泛素蛋白酶体途径、细胞周期和细胞周期依赖性激酶1通路密切相关。HSP90AA1基因与肥大细胞(R=-0.35、P<2.2e^(-16))、活化B淋巴细胞(R=-0.31、P<2.2e^(-16))、效应记忆CD8T淋巴细胞(R=-0.30、P<2.2e^(-16))、NK细胞浸润呈负相关(R=-0.26、P=8.01e-19)。结论血浆HSP-90α表达水平可以作为诊断乳腺良恶性肿瘤的良好指标,HSP90AA1基因与多种信号通路调控关系密切,且与免疫细胞浸润相关,可能是乳腺癌防治的重要靶点。

聚蛋白聚糖促进乳腺癌进展的作用及其机制研究

目的探讨聚蛋白聚糖(aggrecan,ACAN)在泛癌中的表达,并聚焦乳腺癌分析其临床预后意义、免疫细胞浸润及功能富集分析。方法采用生物信息学分析ACAN在多种肿瘤组织及正常组织中的表达、临床预后;运用GEPIA 2、UALCAN、The Human Protein Altas多组学数据库分析ACAN在乳腺癌和正常乳腺组织中的表达;采用TCGA数据库分析ACAN在乳腺癌中的表达水平与临床病理参数及预后的关系;利用TIMER2.0数据库分析ACAN在乳腺癌中的表达水平与免疫细胞浸润的关系,并进一步了解ACAN与免疫检查点的关系;利用GeneMANIA和STRING数据库构建ACAN基因与蛋白质互作网络;运用Metascape数据库对ACAN相关基因进行功能富集分析。结果ACAN在多种肿瘤组织中差异表达,在乳腺癌组织中呈现高表达且为预后不良因素(P<0.05);ACAN高表达与T、B淋巴细胞低浸润、巨噬细胞和中性粒细胞高浸润相关(P<0.05);ACAN与ADAMTS4、ADAMTS5、HAPLN1及COMP相互作用并参与人体多种生物学过程。结论ACAN在乳腺癌中表达水平增高,且ACAN高表达的乳腺癌患者预后较差,其机制可能与抑制T、B淋巴细胞浸润,促进巨噬细胞、中性粒细胞浸润有关。

Expression level of novel tumor suppressor gene FATS is associated with the outcome of node positive breast cancer

Background Recently, we reported the identification of a previously uncharacterized and evolutionarily conserved gene, fragile-site associated tumor suppressor （FATS）, at a frequently deleted region in irradiation （IR）-induced tumors. However, the role of FATS in breast cancer development and its clinical significance has not been defined. The aim of this study was to determine the role of FATS in breast cancer development and to evaluate its clinical significance in breast cancer. Methods The expression level of FATS mRNA was determined in 106 breast carcinomas and 23 paired normal breast tissues using quantitative real time reverse transcription-polymerase chain reaction （RT-PCR）. The relationship between FATS expression and clinicopathological parameters were also analyzed. Results The mRNA level of FATS was down-regulated in breast cancer compared with paired normal tissues. Low expression of FATS was correlated with high nuclear grade. There was a tendency to a favorable outcome for patients with high expression of FATS （P=0.346）. However, low expression of FATS was associated with poor outcome of breast cancer patients with node positive （P=0.011）. Furthermore, the mRNA level of FATS showed an independent value in predicting the outcome of breast cancer patients with positive lymph nodes. Conclusion FATS is involved in the carcinogenesis and development of breast cancer and could be a potential biomarker and prognostic factor for breast cancer therapy.

乳腺癌患者肿瘤转移相关基因1表达与化疗敏感性及预后的相关性

目的研究乳腺癌患者肿瘤转移相关基因1(MTA1)表达与化疗敏感性及预后的相关性。方法选取92例接受乳腺癌根治术的患者作为研究对象,根据患者术后化疗结果分为敏感组和抵抗组,比较2组患者的MTA1表达水平以及相关病理参数,采用logistic回归分析影响患者化疗敏感性的因素,同时根据随访结果分析MTA1表达水平与患者预后的相关性。结果92例化疗患者中敏感组患者共53例,抵抗组共39例。敏感组患者MTA1高表达率低于抵抗组(P<0.05)。敏感组患者中年龄<55岁、KPS评分≥80分、肿瘤分期Ⅰ/Ⅱ期患者占比高于抵抗组(P<0.05)。Logistic回归分析结果显示年龄≥55岁、Karnofsky功能状态评分(KPS)<80分、肿瘤分期Ⅲ期以及MTA1高表达状态均是影响化疗敏感性的高危因素(P<0.05)。MTA1高表达组中位PFS为8个月以及中位OS为13个月,低表达组的中位PFS为12个月以及中位OS为16.5个月,差异比较具有统计学意义(P<0.05)。结论乳腺癌患者MTA1表达与化疗效果有关,其高表达提示化疗不敏感和预后不良,可能成为预测患者预后的重要指标。

人乳腺癌中3种耐药基因产物的表达及其与预后的相关性

目的 研究多药耐药基因产物P-糖蛋白(P-gp)、谷胱甘肽-S转移酶π(GST-π)和DNA拓扑异构酶Ⅱα (TopoⅡα)在乳腺癌组织中的表达及其与预后指标的关系。方法 采用免疫组织化学技术,检测105例乳腺癌 中P-gp、GST-π和TopoⅡα耐药基因蛋白。结果(1)105例乳腺癌中P-gp、GST-π和TopoⅡα的阳性表达率分 别为77.1％、76.2％和36.2％;(2)P-gp及GST-π高表达和TopoⅡ α的低表达与肿瘤的浸润性和腋窝淋巴结转 移相关;(3)P-gp、GST-π和TopoⅡα与C-erbB-2的表达显著正相关;(4)GST-π与ER、PR的表达呈负相关。结 论P-gp、GST-π和TopoⅡα在乳腺癌的表达与其预后指标存在一定的联系,对乳腺癌患者在化疗前进行耐药 基因检测,有助于判断预后及选择合理的化疗方案,从而提高疗效。

乳腺癌组织中C-erbB-2、nm23基因的表达及其预后的关系

目的探讨乳腺癌组织中C-erbB-2基因和nm23基因的表达与预后的关系。方法采用免疫组织化学S-P法检测298例乳腺癌C-erbB-2、nm23基因表达情况并与乳腺癌病理类型、发病年龄、临床分期、腋淋巴结转移情况及5a生存率之间的关系进行分析。结果C-erbB-2基因阳性率36.24%(108/298),nm23基因阳性率为58.05%(173/298);C-erbB-2和nm23基因的表达与肿瘤病理类型、发病年龄、临床分期无明显相关性(P>0.05);C-erbB-2基因表达与腋淋巴结转移呈正相关,与5a生存率呈负相关,nm23基因的表达与腋淋巴结转移呈负相关,与5a生存率呈正相关(P<0.05);C-erbB-2基因表达与nm23基因表达两者之间明显负相关(P<0.05)。结论联合检测乳腺癌组织中C-erbB-2和nm23基因表达可能成为预测、评估乳腺癌患者临床预后的标记物。

三阴性乳腺癌的研究进展

三阴性乳腺癌(triple negative breast cancer,TNBC)是指雌激素受体(estrogen receptor,ER)、孕激素受体(proges-terone receptor,PR)与人类表皮生长因子受体2(human epidermal growth factor receptor-type2,Her-2)均为阴性的一类乳腺癌,其具有侵袭性生物学行为及临床病理特征的一个乳腺癌亚型,与基底细胞样乳腺癌和乳腺癌易感癌基因1(breast cancer suscep-tibitity genel,BRCAI)相关性乳腺癌有一定相关性。此类型乳腺癌对常规标准治疗效果欠佳,易发生远处转移,预后较其他类型乳腺癌差。对TNBC的深入研究,将有助于人们采取有效的治疗方法来提高其疗效。

CD44v6、E-cadhesion表达与乳腺浸润性癌预后的关系

目的检测CD44v6、E-cad在乳腺浸润性癌中的表达情况,探讨它们与乳腺浸润性癌浸润和转移的关系。方法采用免疫组化SP法检测103例乳腺浸润性癌中CD44v6、E-cad的表达,结合病理指标和临床指标分析其与预后的关系。结果CD44v6蛋白表达在细胞浆和(或)细胞膜上,阳性表达率为76.7%(79/103)。E-cad蛋白表达主要见于细胞膜,阳性表达率为35.0%(36/103)。CD44v6、E-cad蛋白表达与乳腺浸润性癌组织学类型无关(P>0.05),与组织学分级及组织浸润程度有关(P<0.05)。在56例有随访记录的患者中,CD44v6、E-cad蛋白表达与患者年龄无关(P>0.05),与腋窝淋巴结转移、局部复发、远处转移均有关(P<0.05)。两者在同一癌组织中的表达呈负相关(P<0.01)。结论CD44v6、E-cad蛋白表达与腋窝淋巴结转移、局部复发、远处转移有关(P<0.05),因此CD44v6、E-cad蛋白表达可作为判断乳腺浸润性癌的浸润程度、预测预后的参考指标之一。

三阴性乳腺癌中程序性细胞死亡基因4表达及其与预后的关系

目的探讨三阴性乳腺癌中程序性细胞死亡基因4(programmed cell death gene 4,PDCD4)的表达及其与患者预后的关系。方法收集广东省妇幼保健院乳腺科2007年1月至2012年12月间收治的随访资料完整的三阴性乳腺癌患者共176例,均为女性,中位年龄44岁。采用免疫组化方法检测PDCD4的表达;采用Kaplan-meier法对患者的无病生存及总生存情况进行分析,并运用Cox回归法探讨影响三阴性乳腺癌生存预后的因素。结果 176例患者中,PDCD4表达阳性者79例(44.8%),显著低于癌旁组织阳性表达率(90.0%,P=0.005)。PDCD4表达缺失与年龄无关(P>0.05),而与肿瘤直径、淋巴结转移个数及组织学分级相关(P<0.05),肿瘤越大(r=-0.270,P<0.001)、淋巴结转移越多(r=-0.240,P=0.001)、组织学分级越高(r=-0.206,P=0.006),PDCD4阳性表达率越低。中位随访时间42个月,单因素分析显示PDCD4表达阳性者其无病生存率及总生存率均优于表达阴性者(P<0.05)。多因素分析显示PDCD4表达、肿瘤直径及分期是影响三阴性乳腺癌预后的独立因素(P<0.05)。结论三阴性乳腺癌中PDCD4表达缺失与预后不良相关,PDCD4可作为评估三阴性乳腺癌预后的指标。

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后的影响。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％（２５／４例），其与月经状况、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分析却显示仅有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。