PYCARD基因在乳腺癌的表达情况及预后分析

乳腺癌是全球女性最常见的恶性肿瘤,准确的早期诊断和预后生物标志物可以提高治疗的效率.细胞凋亡相关的斑点样蛋白(apoptosis-associated specklike protein,ASC)是一种衔接蛋白,在肿瘤发生中有重要的作用.为了进一步探究ASC的作用机制,通过分析ASC蛋白的编码基因PYCARD在Oncomine数据库mRNA表达情况,MethHC数据库分析甲基化水平,bc-GenExMiner v4.3分析PYCARD在不同乳腺癌类型中的表达情况,再利用PrognoScan数据库分析PYCARD与乳腺癌患者预后的关系,并发现PYCARD基因在乳腺癌中8例高表达,癌症组织中PYCARD的甲基化水平比正常组织显著升高,乳腺癌患者PYCRAD基因与临床病理参数有关系.预后结果分析发现PYCARD mRNA高表达患者在总生存期(overall survival,OS)、无远处转移生存率(distant metastasis free survival,DMFS)、和无复发生存期存活率(relapse free survival,RFS)上高于低表达患者.PYCARD基因在乳腺癌高表达,而预后结果又显示高表达患者的存活率高于低表达,这很有可能与PYCARD基因甲基化水平有关.本研究在指导乳腺癌治疗和评估预后方面具有一定临床意义.     

Deregulated Expression of Aurora Kinases Is Not a Prognostic Biomarker in Papillary Thyroid Cancer Patients

A number of reports indicated that Aurora-A or Aurora-B overexpression represented a negative prognostic factor in several human malignancies. In thyroid cancer tissues a deregulated expression of Aurora kinases has been also demonstrated, butno information regarding its possible prognostic role in differentiated thyroid cancer is available. Here, weevaluated Aurora-A and Aurora-B mRNA expression and its prognostic relevance in a series of 87 papillary thyroid cancers (PTC), with a median follow-up of 63 months. The analysis of Aurora-A and Aurora-B mRNA levels in PTC tissues, compared to normal matched tissues, revealed that their expression was either up- or down-regulatedin the majority of cancer tissues. In particular, Aurora-A and Aurora-B mRNA levels were altered, respectively, in 55 (63.2%) and 79 (90.8%) out of the 87 PTC analyzed.A significant positive correlation between Aurora-A and Aurora-B mRNAswas observed (p=0.001). The expression of both Aurora genes was not affected by the BRAF^V600E mutation. Univariate, multivariate and Kaplan-Mayer analyses documented the lack of association between Aurora-A or Aurora-B expression and clinicopathological parameterssuch as gender, age, tumor size, histology, TNM stage, lymph node metastasis and BRAF status as well asdisease recurrences or disease-free interval. Only Aurora-B mRNA was significantly higher in T(3-4) tissues, with respect to T(1-2) PTC tissues. The data reported here demonstrate that the expression of Aurora kinases is deregulated in the majority of PTC tissues, likely contributing to PTC progression. However, differently from other human solid cancers, detection of Aurora-A or Aurora-B mRNAs is not a prognostic biomarker inPTC patients.     

Nucleobindin-2 在乳腺癌中表达的临床病理意义

目的:探讨NUCB2在乳腺癌中的表达及临床病理意义。方法:收集乳腺癌病例及相应的临床资料包括随访资料应用免疫组织化学技术检测良性病变,有/无淋巴结转移的乳腺癌及配对淋巴结转移灶中NUCB2的表达,分析NUCB2表达与乳腺癌临床病理指标和生存状态间的关系。结果:免疫组化结果:显示NUCB2在BBD、MBC、NMBC、PMLN的阳性表达率分别为90.0%(45/50),82.1%(87/106)、48.2%(40/83)、47.2%(50/106)。其中,NUCB2在BBD的阳性表达率显著高于NMBC、PMLN,而与MBC无显著性差异;在MBC中的阳性表达率显著高于NMBC;在MBC中的阳性表达率显著高于PMLN。临床病理分析结果:显示乳腺癌原发灶中NUCB2表达与淋巴结转移(p=0.000)、临床分期(p=0.001)、雌激素阳性表达(p=0.020)具有显著性相关。而与年龄、肿块大小、组织学分级、组织学类型、孕激素受体、HER2表达、绝经情况无显著相关。Kaplan-Meier分析结果:显示NUCB2阳性表达病例的总生存率比阴性病例更短(P=0.004)。结论:NUCB2在乳腺癌中表达与淋巴结转移、临床分期、雌激素受体表达和生存状态相关,可能在乳腺癌恶性演进和预后中具有重要意义。     

The Prognostic Significance of Wnt-5a Expression in Primary Breast Cancer Is Extended to Premenopausal Women

Wnt-5a protein expression in primary tumors from unselected breast cancer patients has revealed a tumor suppressive function of the protein. However, in vitro experiments on human breast cancer cells have reported contradictory results, indicating both a tumor suppressive and promoting functions of Wnt-5a. This could be due to various functions of Wnt-5a in different subgroups of patients. The unselected cohorts analyzed to date for Wnt-5a protein expression contained few premenopausal patients. The aim of the present investigation was to evaluate the prognostic significance of Wnt-5a protein expression in a cohort of premenopausal women with comprehensive data on biomarkers, molecular subtypes and long-term outcome. In a randomized trial of adjuvant tamoxifen versus no adjuvant treatment, 564 premenopausal primary breast cancer patients were included. The median follow-up time was 14 years. A tumor tissue array was constructed and 361 samples were evaluated for Wnt-5a reactivity by immunohistochemistry. The primary end-point was recurrence-free survival. Wnt-5a protein expression was reduced or lost in 146/361 of tumors and correlated to younger age, estrogen receptor (ER) negativity and triple-negative phenotype. Wnt-5a was a prognostic factor in the whole cohort (p = 0.003). In patients with ER-positive tumors, Wnt-5a was an independent positive prognostic marker (HR 0.51 95% CI: 0.33–0.78 p = 0.002) and HER2 a negative prognostic marker (HR 2.84 95% CI: 1.51–5.31, p = 0.001) in a Cox multivariate analysis adjusted for standard prognostic markers and tamoxifen treatment. In the ER-negative subset, Wnt-5a added no prognostic information. In a subgroup analysis, Wnt-5a was significantly associated with better prognosis in patients with Luminal A tumors (p = 0.04). Conclusively, our results suggest that loss of Wnt-5a is a valuable prognostic marker in premenopausal breast cancer patients in particular in patients with ER-positive tumors and out-performed conventional prognostic factors in this subset of patients.     

Prognostic Significance of High VEGF-C Expression for Patients with Breast Cancer: An Update Meta Analysis

BackgroundThe prognostic significance of vascular endothelial growth factor C (VEGF-C) expression in breast cancer (BC) patients remains controversial. Therefore, this meta-analysis was performed to determine the prognostic significance of VEGF-C expression in BC patients.ResultsThe present meta analysis totally included 21 eligible studies and 2828 patients with BC. The combined HRs were 1.87(95% CI 1.25–2.79, P = 0.001) for DFS and 1.96(95% CI 1.15–3.31, P = 0.001) for OS. The pooled HRs of non-Asian subgroup were 2.04(95%CI 1.36–3.05, P = 0.001) for DFS and 2.61(95%CI 1.51–4.52, P = 0.001) for OS, which were significantly higher than that of Asian subgroup. The funnel plot for publication bias was symmetrical. The further Egger''s test and Begg''s test did not detect significant publication bias (all P>0.05).ConclusionsThe present meta analysis strongly supported the prognostic role of VEGF-C expression for DFS and OS in BC patients, especially for patients in non-Asian countries. Furthermore, stratification by VEGF-C expression may help to optimize the treatments and the integrated managements for BC patients.     

Prognostic Typing in Breast Cancer

Infiltrating breast carcinomas in which recurrence takes place 10 years or more after operation are reported to contain tumour cells of characteristic morphology. The cytological features of these tumour cells form the basis of the system of classification described here. Three cytological types are recognized, prognosis being best in type III. Typing is carried out on specimens stained with haematoxylin and eosin. The results of typing were reproducible in over 90% of cases and independent of the histology of the lesion. Correlation to survival time was shown in a total of 222 cases.     

Role of Deregulated microRNAs in Breast Cancer Progression Using FFPE Tissue

MicroRNAs (miRNAs) contribute to cancer initiation and progression by silencing the expression of their target genes, causing either mRNA molecule degradation or translational inhibition. Intraductal epithelial proliferations of the breast are histologically and clinically classified into normal, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). To better understand the progression of ductal breast cancer development, we attempt to identify deregulated miRNAs in this process using Formalin-Fixed, Paraffin-Embedded (FFPE) tissues from breast cancer patients. Following tissue microdissection, we obtained 8 normal, 4 ADH, 6 DCIS and 7 IDC samples, which were subject to RNA isolation and miRNA expression profiling analysis. We found that miR-21, miR-200b/c, miR-141, and miR-183 were consistently up-regulated in ADH, DCIS and IDC compared to normal, while miR-557 was uniquely down-regulated in DCIS. Interestingly, the most significant miRNA deregulations occurred during the transition from normal to ADH. However, the data did not reveal a step-wise miRNA alteration among discrete steps along tumor progression, which is in accordance with previous reports of mRNA profiling of different stages of breast cancer. Furthermore, the expression of MSH2 and SMAD7, two important molecules involving TGF-β pathway, was restored following miR-21 knockdown in both MCF-7 and Hs578T breast cancer cells. In this study, we have not only identified a number of potential candidate miRNAs for breast cancer, but also found that deregulation of miRNA expression during breast tumorigenesis might be an early event since it occurred significantly during normal to ADH transition. Consequently, we have demonstrated the feasibility of miRNA expression profiling analysis using archived FFPE tissues, typically with rich clinical information, as a means of miRNA biomarker discovery.     

PRRX1蛋白在乳腺癌中的表达及其临床意义

目的:探讨配对相关同源框1(PRRX1)在乳腺癌中的表达及其临床病理学意义,为乳腺癌的诊断和治疗提供参考依据。方法:收集2002~2003年湖南省肿瘤医院收治的临床资料及随访资料完整的80例乳腺癌组织标本,应用免疫组织化学技术检测乳腺癌和癌旁正常乳腺组织中PRRX1的表达,并分析PRRX1表达与乳腺癌患者临床病理特征间的关系。结果:PRRX1在80例乳腺癌中的阳性表达率是45%(36/80),在癌旁组织中的阳性表达率为12.5%(5/40),二者比较有显著性差异(P0.05)。PRRX1的阳性表达率与乳腺癌患者的年龄、组织学类型、肿瘤分化程度均无显著性相关(P0.05),而与淋巴结转移、临床分期显著相关(P0.05),淋巴结转移及Ⅲ~Ⅳ期乳腺癌患者PRRX1的阳性表达率显著高于无淋巴结转移及Ⅰ~Ⅱ期的乳腺癌患者(P0.05)。PRRX1表达阴性的乳腺癌患者5年生存率显著高于PRRX1表达阳性的乳腺癌患者(P0.05)。结论:乳腺癌中PRRX1的表达上调与其发生和恶性演进密切相关,可能作为乳腺癌诊断和预后预测的候选标志物。     

Prognostic Significance of MYH9 Expression in Resected Non-Small Cell Lung Cancer

Introduction

Myosin-9 (MYH9) belongs to the myosin superfamily of actin-binding motor protein. Recently, MYH9 has been thought to be associated with cancer cell migration, invasion, and metastasis. The aims of this study were to immunohistochemically examine MYH9 expression in surgically resected non-small cell lung cancer (NSCLC), and evaluate its correlations with clinicopathological parameters and the prognosis of patients.

Methods

MYH9 expression was immunohistochemically studied in 266 consecutive resected NSCLCs, and its associations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of MYH9 expression on survival.

Results

MYH9 expression was detected in 102 of 266 (38.3%) NSCLCs. MYH9 expression was significantly correlated with the adenocarcinoma histology (P = 0.014), poorer differentiation ((P = 0.033), intratumoral vascular invasion and lymphatic invasion ((P = 0.013 and P = 0.045 respectively), and a poorer prognosis ((P = 0.032). In addition, multivariable analysis revealed that MYH9 expression independently predicted a poorer survival (HR, 2.15; 95%CI, 1.17-3.92; (P = 0.01).

Conclusion

The present study revealed that MYH9 is expressed in a subset of NSCLC with a more malignant nature, and its expression is an indicator of a poorer survival probability.     

乳腺癌中丝／苏氨酸蛋白激酶Plk1mRNA的表达及其预后价值

目的：检测乳腺癌细胞和组织中丝／苏氨酸蛋白激酶Plk1基因mRNA的表达情况并分析其预后价值。方法：应用半定量RT-PCR方法分析3株人乳腺癌细胞和1株正常乳腺上皮细胞中Plk1基因mRNA的表达水平。同时分析84例乳腺癌及对应的癌旁正常乳腺上皮组织中Plk1mRNA的表达水平。统计学分析Plk1mRNA表达水平与乳腺癌患者年龄、肿瘤大小、组织分化程度、淋巴结转移状况、TNM分期和雌激素受体（ER）等临床病理参数之间的关系,以及与预后之间的关系。结果：Plk1基因mRNA在乳腺癌细胞中的相对表达水平显著高于其在正常乳腺上皮细胞中的相对表达水平（P值均小于〈0．05）。另外,Plk1mRNA在乳腺癌组织中平均表达水平（0．88±0．18）显著高于其在癌旁正常乳腺上皮组织中平均表达水平（0．22±0．10;P〈0．01）。统计学分析结果袁明：Plk1mRNA表达水平和乳腺癌患者的淋巴结转移状况及TNM分期密切相关（P=0．009或0．007）。Kaplan—Meier生存曲线分析结果表明：高Plk1mRNA表达水平的乳腺癌患者的5年无疾病进展率及总体生存率均显著低于低Plk1mRNA表达水平的乳腺癌患者（P=0．0026及0．0136）。COX模型的多因素预后分析结果表明：Plk1基因mRNA表达水平是乳腺癌患者的一个独立的预后因素（HR=4．764,95％CI：1．341-6．123,P=0．0025）。结论：Plk1在乳腺癌组织呈现高表达水平,其mRNA表达水平有望成为临床乳腺癌患者一个重要的预后判断分子指标。     

乳腺癌中丝/ 苏氨酸蛋白激酶Plk1 mRNA 的表达及其预后价值

目的:检测乳腺癌细胞和组织中丝/苏氨酸蛋白激酶Plk1基因mRNA的表达情况并分析其预后价值。方法:应用半定量RT-PCR方法分析3株人乳腺癌细胞和1株正常乳腺上皮细胞中Plk1基因mRNA的表达水平。同时分析84例乳腺癌及对应的癌旁正常乳腺上皮组织中Plk1 mRNA的表达水平。统计学分析Plk1 mRNA表达水平与乳腺癌患者年龄、肿瘤大小、组织分化程度、淋巴结转移状况、TNM分期和雌激素受体(ER)等临床病理参数之间的关系,以及与预后之间的关系。结果:Plk1基因mRNA在乳腺癌细胞中的相对表达水平显著高于其在正常乳腺上皮细胞中的相对表达水平(P值均小于<0.05)。另外,Plk1 mRNA在乳腺癌组织中平均表达水平(0.88±0.18)显著高于其在癌旁正常乳腺上皮组织中平均表达水平(0.22±0.10;P<0.01)。统计学分析结果表明:Plk1 mRNA表达水平和乳腺癌患者的淋巴结转移状况及TNM分期密切相关(P=0.009或0.007)。Kaplan-Meier生存曲线分析结果表明:高Plk1 mRNA表达水平的乳腺癌患者的5年无疾病进展率及总体生存率均显著低于低Plk1 mRNA表达水平的乳腺癌患者(P=0.0026及0.0136)。COX模型的多因素预后分析结果表明:Plk1基因mRNA表达水平是乳腺癌患者的一个独立的预后因素(HR=4.764,95%CI:1.341~6.123,P=0.0025)。结论:Plk1在乳腺癌组织呈现高表达水平,其mRNA表达水平有望成为临床乳腺癌患者一个重要的预后判断分子指标。     

Prognostic Value of Mitotic Index and Bcl2 Expression in Male Breast Cancer

The incidence of male breast cancer (MBC) is rising. Current treatment regimens for MBC are extrapolated from female breast cancer (FBC), based on the assumption that FBC prognostic features and therapeutic targets can be extrapolated to MBC. However, there is yet little evidence that prognostic features that have been developed and established in FBC are applicable to MBC as well. In a recent study on FBC, a combination of mitotic index and Bcl2 expression proved to be of strong prognostic value. Previous papers on Bcl2 expression in MBC were equivocal, and the prognostic value of Bcl2 combined with mitotic index has not been studied in MBC. The aim of the present study was therefore to investigate the prognostic value of Bcl2 in combination with mitotic index in MBC. Immunohistochemical staining for Bcl2 was performed on tissue microarrays of a total of 151 male breast cancer cases. Mitotic index was scored. The prognostic value of Bcl2 expression and Bcl2/mitotic index combinations was evaluated studying their correlations with clinicopathologic features and their prediction of survival. The vast majority of MBC (94%) showed Bcl2 expression, more frequently than previously described for FBC. Bcl2 expression had no significant associations with clinicopathologic features such as tumor size, mitotic count and grade. In univariate survival analysis, Bcl2 had no prognostic value, and showed no additional prognostic value to tumor size and histological grade in Cox regression. In addition, the Bcl2/mitotic index combination as opposed to FBC did not predict survival in MBC. In conclusion, Bcl2 expression is common in MBC, but is not associated with major clinicopathologic features and, in contrast to FBC, does not seem to have prognostic value, also when combined with mitotic index.     

Functional Analysis of Prognostic Gene Expression Network Genes in Metastatic Breast Cancer Models

Identification of conserved co-expression networks is a useful tool for clustering groups of genes enriched for common molecular or cellular functions [1]. The relative importance of genes within networks can frequently be inferred by the degree of connectivity, with those displaying high connectivity being significantly more likely to be associated with specific molecular functions [2]. Previously we utilized cross-species network analysis to identify two network modules that were significantly associated with distant metastasis free survival in breast cancer. Here, we validate one of the highly connected genes as a metastasis associated gene. Tpx2, the most highly connected gene within a proliferation network specifically prognostic for estrogen receptor positive (ER+) breast cancers, enhances metastatic disease, but in a tumor autonomous, proliferation-independent manner. Histologic analysis suggests instead that variation of TPX2 levels within disseminated tumor cells may influence the transition between dormant to actively proliferating cells in the secondary site. These results support the co-expression network approach for identification of new metastasis-associated genes to provide new information regarding the etiology of breast cancer progression and metastatic disease.     

WDR5 Expression Is Prognostic of Breast Cancer Outcome

WDR5 is a core component of the human mixed lineage leukemia-2 complex, which plays central roles in ER positive tumour cells and is a major driver of androgen-dependent prostate cancer cell proliferation. Given the similarities between breast and prostate cancers, we explore the potential prognostic value of WDR5 gene expression on breast cancer survival. Our findings reveal that WDR5 over-expression is associated with poor breast cancer clinical outcome in three gene expression data sets and BreastMark. The eQTL analysis reveals 130 trans-eQTL SNPs whose genes mapped with statistical significance are significantly associated with patient survival. These genes together with WDR5 are enriched with “cellular development, gene expression, cell cycle” signallings. Knocking down WDR5 in MCF7 dramatically decreases cell viability, but does not alter tumour cell response to doxorubicin. Our study reveals the prognostic value of WDR5 expression in breast cancer which is under long-range regulation of genes involved in cell cycle, and anthracycline could be coupled with treatments targeting WDR5 once such a regimen is available.     

Cep55在基底细胞样乳腺癌中的表达及其临床意义

目的:探讨中心体相关蛋白Cep55在基底细胞样型乳腺癌中的表达及其与基底细胞样型乳腺癌临床病理特征的关系.方法:选取本院收集的66例基底细胞样型乳腺癌和66例癌旁正常乳腺组织标本后,运用石蜡包埋、切片后,采用免疫组化法(EnVision二步法)检测Cep55的表达,并分析其与基底细胞样型乳腺癌临床病理特征之间的相关性.结果:(1)基底细胞样型乳腺癌和癌旁正常乳腺组织中Cep55的阳性表达率分别为74.2％和16.7％,差异有统计学意义(P＜0.05).(2)不同的年龄、绝经与否、肿块大小的基底细胞样型乳腺癌患者Cep55的表达无明显差异(P＞0.05),不同TNM分期、淋巴结转移与否的基底细胞样型乳腺癌患者Cep55的表达比较差异有显著统计学意义(P＜0.05).结论:Cep55的表达上调与基底细胞样型乳腺癌的发生和发展有关.     

Insulin Receptor Substrate Adaptor Proteins Mediate Prognostic Gene Expression Profiles in Breast Cancer

Therapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins. IRS-null breast cancer cells (T47D-YA) were engineered to express IRS-1 or IRS-2 alone and their ability to mediate IGF ligand-induced proliferation, motility, and gene expression determined. Global gene expression signatures reflecting IRS adaptor specific and primary vs. secondary ligand response were derived (Early IRS-1, Late IRS-1, Early IRS-2 and Late IRS-2) and functional pathway analysis examined. IRS isoforms mediated distinct gene expression profiles, functional pathways, and breast cancer subtype association. For example, IRS-1/2-induced TGFb2 expression and blockade of TGFb2 abrogated IGF-induced cell migration. In addition, the prognostic value of IRS proteins was significant in the luminal B breast tumor subtype. Univariate and multivariate analyses confirmed that IRS adaptor signatures correlated with poor outcome as measured by recurrence-free and overall survival. Thus, IRS adaptor protein expression is required for IGF ligand responses in breast cancer cells. IRS-specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer.     

Clinical and Prognostic Significance of Preoperative Plasma Fibrinogen Levels in Patients with Operable Breast Cancer

Purpose

Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer.

Methods

Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS) and overall survival(OS). Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS.

Results

Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001), menopause (yes vs. no, p<0.001), tumor size (T1&T2 vs.T3&T4, p = 0.033), tumor stage (Ⅰvs.Ⅱvs.Ⅲ, p = 0.034) and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001), but not with histological grade, molecular type and other Immunohistochemical parameters(ER, PR, HER2 and Ki-67). In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/ p<0.001)and plasma fibrinogen (p<0.001/ p<0.001) levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6–5.3/ p = 0.006, HR = 3.2, 95% CI = 1.4–7.3) and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4–8.3/ p = 0.002, HR = 10.1, 95% CI = 2.3–44.6) were associated with disease-free and overall survival in a multivariate survival analysis, respectively.

Conclusions

This study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer.     

三阴性乳腺癌中环状RNA的表达特点及功能意义

环状RNA是由前体RNA通过反向剪接形成的一类共价闭合环状分子.在过去,环状RNA被认为是DNA转录的"噪音",不参与生物代谢过程.然而,最近研究表明,环状RNA的异常表达可影响包括三阴性乳腺癌在内的多种恶性肿瘤的发生发展.该文综述了环状RNA在肿瘤中的分子机制及其在三阴性乳腺癌细胞增殖、凋亡、迁移、侵袭和药物抗性中的...