Circulating miR-148b and miR-133a as biomarkers for breast cancer detection

Circulating microRNAs have drawn a great deal of attention as promising novel biomarkers for breast cancer. However, to date, the results are mixed. Here, we performed a three-stage microRNA analysis using plasma samples from breast cancer patients and healthy controls, with efforts taken to address several pitfalls in detection techniques and study design observed in previous studies. In the discovery phase with 122 Caucasian study subjects, we identified 43 microRNAs differentially expressed between breast cancer cases and healthy controls. When those microRNAs were compared with published data from other studies, we identified three microRNAs, including miR-148b, miR-133a and miR-409-3p, whose plasma levels were significantly higher in breast cancer cases than healthy controls and were also significant in previous independent studies. In the validation phase with 50 breast cancer cases and 50 healthy controls, we validated the associations with breast cancer detection for miR-148b and miR-133a (P = 1.5×10⁻⁶ and 1.3×10⁻¹⁰, respectively). In the in-vitro study phase, we found that both miR-148b and miR-133a were secreted from breast cancer cell lines, showing their secretory potential and possible tumor origin. Thus, our data suggest that both miR-148b and miR-133a have potential use as biomarkers for breast cancer detection.     

Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients

Background:

Owing to late diagnosis in advanced disease stages, prognosis of patients with epithelial ovarian cancer (EOC) is poor. The quantification of deregulated levels of microRNAs could facilitate earlier diagnosis and improve prognosis of EOC.

Methods:

Seven microRNAs (miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429) were quantified in the serum of 180 EOC patients and 66 healthy women by TaqMan PCR microRNA assays. Median follow-up time was 21 months. The effects of miR-7 and miR-429 on apoptosis, cell proliferation, migration and invasion were investigated in two (EOC) cell lines.

Results:

Serum levels of miR-25 (P=0.0001) and miR-93 (P=0.0001) were downregulated, whereas those of miR-7 (P=0.001) and miR-429 (P=0.0001) were upregulated in EOC patients compared with healthy women. The four microRNAs discriminated EOC patients from healthy women with a sensitivity of 93% and a specificity of 92%. The levels of miR-429 positively correlated with CA125 values (P=0.0001) and differed between FIGO I–II and III–IV stages (P=0.001). MiR-429 was an independent predictor of overall survival (P=0.011). Overexpressed miR-429 in SKOV3 cells led to suppression of cell migration (P=0.037) and invasion (P=0.011). Increased levels of miR-7 were associated with lymph node metastases (P=0.0001) and FIGO stages III–IV (P=0.0001). Overexpressed miR-7 in SKOV3 cells resulted in increased cell migration (P=0.001) and invasion (P=0.011). Additionally, the increased levels of miR-376a correlated with FIGO stages III–IV (P=0.02).

Conclusions:

Our data indicate the diagnostic potential of miR-7, miR-25, miR-93 and miR-429 in EOC and the prognostic potential of miR-429. This microRNA panel may be promising molecules to be targeted in the treatment of EOC.     

血清中miR-155与乳腺癌的相关性

目的分析血清中miR-155的表达水平,探讨其与乳腺癌临床病理特征之间的关系。方法收集2010年12月至2011年4月入院的67例女性患者（乳腺癌45例,非乳腺癌22例）的血液标本,分离血清并提取miRNA,通过荧光实时定量PCR法检测血清中miR-155的表达水平,分析其与乳腺癌临床病理特征间的相关性。结果乳腺癌患者相比非乳腺癌患者,腋窝淋巴结转移阳性乳腺癌患者相比阴性患者血清中miR-155表达水平均上调（均P〈0．05）;在乳腺癌患者中,肿瘤大小为T1的相比T2和r乃患者,I、Ⅱ期相比Ⅲ期患者,ER、PR阳性相比阴性患者血清中的miR-155表达水平均下调（均P〈0．05）。结论血清中miR．155的表达水平与乳腺癌及其临床病理特征密切相关。miR-155可成为新-代的乳腺癌标志物,并为乳腺癌发病机制及治疗和预后判断研究提供-个新方向。     

Analysis of miR-205 and miR-155 expression in the blood of breast cancer patients

The purpose of this study was to identify and validate circulating microRNAs (miRNAs) in human plasma for use as breast cancer (BC) biomarkers and to analyze their relationship to clinicopathologic features and its preliminary biological function. Genome-wide expression profiling of miRNAs in BC was investigated by microarray analysis. miR-155 was up-regulated greater than two-fold in BC compared with Normal Adjacent Tissue (NAT), whereas let-7b, miR-381, miR-10b, miR-125a-5p, miR-335, miR-205 and miR-145 were down- regulated greater than two-fold. Our hypothesis was that circulating miRNAs are also present and differentially expressed in the serum of BC patients compared to controls. Using real-time PCR (RT-PCR), we analyzed miR-205 and miR-155 in archived serum from 30 participants, 20 with breast cancer and 10 healthy people. miR-205 was down-regulated in BC patient serum while miR-155 was up-regulated. Furthermore, we analyzed the relationship between the expression levels of these two miRNAs and the clinicopathologic parameters of BC patients. High expression of miR155 was associated with clinical stage, molecular type, Ki-67 and p53 in BC patients (P<0.05). By contrast, we found no significant correlation between miR-205 and BC patient clinicopathologic parameters. Functional analysis showed that ectopic expression of miR-205 significantly inhibits cell proliferation and promotes apoptosis. miR-205 was down-regulated and miR-155 was up-regulated in BC patient serum. miR-155 was positive correlated with clinical stage and ki-67 and negatively correlated with p53 status.     

Circulating tumour cells in the central and the peripheral venous compartment in patients with metastatic breast cancer

Background:

The enumeration of circulating tumour cells (CTC) has prognostic significance in patients with metastatic breast cancer (MBC) and monitoring of CTC levels over time has considerable potential to guide treatment decisions. However, little is known on CTC kinetics in the human bloodstream.

Methods:

In this study, we compared the number of CTC in both 7.5 ml central venous blood (CVB) and 7.5 ml peripheral venous blood (PVB) from 30 patients with MBC starting with a new line of chemotherapy.

Results:

The number of CTC was found to be significantly higher in CVB (median: 43.5; range: 0–4036) than in PVB (median: 33; range: 0–4013) (P=0.001). When analysing samples pairwise, CTC counts were found to be significantly higher in CVB than in PVB in 12 out of 26 patients with detectable CTC. In contrast, only 2 out of 26 patients had higher CTC counts in PVB as compared with CVB, whereas in 12 remaining patients no significant difference was seen. The pattern of CTC distribution was independent of the sites of metastatic involvement.

Conclusion:

A substantial difference in the number of CTC was observed between CVB and PVB of patients with MBC. Registration of the site of blood collection is warranted in studies evaluating the role of CTC assessment in these patients.     

宫颈鳞状细胞癌组织LncRNA EXOC7表达与预后相关性研究

目的 宫颈癌是女性生殖系统常见的恶性肿瘤之一.长链非编码RNA(lncRNA)的异常表达与肿瘤的发生、发展密切相关.本研究拟探讨长链非编码RNA外泌体复合物7(Long non-coding RNA Exocyst complex component 7,LncRNA EXOC7)在宫颈鳞状细胞癌(cervical squamous cell cancer,SCC)组织中的表达及临床意义.方法 收集2012-01-01-2016-12-30四川省人民医院肿瘤科及妇产科行手术及穿刺活检的98例SCC患者组织标本,其中癌旁组织(距癌组织＞2 cm)58例;同期收集该院40例正常宫颈组织.采用QRT-PCR法检测SCC组织及癌旁组织标本中Ln-cRNA EXOC7的表达,采用单因素及多因素Cox回归分析LncRNA EXOC7的表达与患者临床病理特征及预后的关系,生存曲线分析LncRNA EXOC7与患者总生存时间(overall survival,OS)及无进展生存时间(progression free survival,PFS)的关系.结果 SCC组织中lncRNA EXOC7的平均表达量为(6.805±1.475),明显高于癌旁组织(1.510±0.860)及正常宫颈组织(1.476±0.33)的平均表达量,差异有统计学意义,F=74.43,P＜0.001.LncRNA EXOC7高表达与患者的FIGO分期、淋巴结转移和肿瘤浸润深度相关,差异均有统计学意义,均P＜0.05;高表达组LncRNA EXOC7患者PFS为(12.00±1.55)个月,较低表达组(27.35±2.25)个月明显缩短,差异有统计学意义,x2=51.650,P＜0.001;高表达组LncRNA EXOC7患者OS为(25.08±3.32)个月,较低表达组(44.80±2.92)个月明显缩短,差异有统计学意义,x2=38.23,P＜0.001;Cox多因素分析显示,LncRNA EXOC7的表达是SCC患者的独立预后因素,HR=3.750,95％CI为1.530～7.97,P＜0.001.结论 高表达LncRNA EXOC7 SCC患者的预后差,LncRNA EXOC7可能作为潜在的SCC治疗靶点及新预后评估分子标志物.     

Expression of cancer-testis antigen CT7 (MAGE-C1) in breast cancer: An immunohistochemical study with emphasis on prognostic utility

High expression of the cancer-testis antigen CT7, also referred to as MAGE-C1, has been recently described in a variety of malignant tumors, including breast carcinoma. To our knowledge, no data concerning the prognostic utility of CT7 expression in breast cancer are available. In this retrospective study, we evaluated the relationship between CT7 immunoreactivity and clinicopathological parameters as well as relapse-free survival (RFS) and metastasis-free survival (MFS) of 124 women with invasive breast cancer. A positive CT7 status, defined as immunoreactivity in more than 50% of tumor cells, was found in 18% of cases and correlated significantly with high tumor grade (p=0.004), but with no other clinicopathological parameter. In a univariate analysis, CT7 status showed an association with RFS by trend (p=0.107; relative risk [RR]: 1.85) and a significant association with MFS (p=0.043; RR: 2.02). In a multivariate analysis, tumor grade, stage, nodal status, angioinvasion, HER2 expression as well as estrogen and progesterone receptor expression were identified as significant independent prognostic factors of RFS and/or MFS. In this respect, CT7 expression showed a weak, statistically not significant trend towards an independent prognostic relevance concerning prediction of MFS (p=0.147; RR: 1.95). Our data suggest that estimation of CT7 immunoreactivity is of limited prognostic usefulness in breast cancer. It may provide additional information concerning assessment of MFS in selected cases.     

Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis

Numerous studies have shown that aberrant microRNA (miRNA) expression is associated with the development and progression of various types of human cancer and serum miRNAs are potential biomarkers. This study examined whether some commonly deregulated miRNAs in hepatocellular carcinoma (HCC) are presented in serum of patients with HCC and can serve as diagnostic markers. Serum miRNAs (miR‐21, miR‐122, and miR‐223) were quantified by real‐time quantitative RT‐PCR in 101 patients with HCC and 89 healthy controls. In addition, 48 patients with chronic type B hepatitis were also analyzed for comparison. We found that the median levels of miR‐21, miR‐122, and miR‐223 were significantly higher in patients with HCC than those in healthy controls (P = 7.48 × 10^?13, P = 6.93 × 10^?9, and P = 3.90 × 10^?12, respectively). However, these elevated serum miRNAs were also detected in patients with chronic hepatitis (P = 2.05 × 10^?12, P = 4.52 × 10^?16, and P = 1.65 × 10^?11, respectively). Moreover, serum miR‐21 and miR‐122 in patients with chronic hepatitis were higher than in patients with HCC (P = 3.99 × 10^?4 and P = 4.97 × 10^?8), although no such significant difference was found for miR‐223. Receiver‐operator characteristic (ROC) curve analyses suggest that these serum miRNAs may be useful markers for discriminating patients with HCC or chronic hepatitis from healthy controls, but not patients with HCC from patients with chronic hepatitis. Our results indicate that serum miR‐21, miR‐122 and miR‐223 are elevated in patients with HCC or chronic hepatitis and these miRNAs have strong potential to serve as novel biomarkers for liver injury but not specifically for HCC. © 2010 Wiley‐Liss, Inc.     

Circulating CA 15-3 levels in the postsurgical follow-up of breast cancer patients and in non-malignant diseases

Summary Circulating CA 15-3 antigen levels were evaluated in patients with benign diseases and breast cancer patients with no clinical evidence of disease after surgery (NED). Patients with breast cancer NED were followed for tumor recurrence or death during a median of 12.9 months (range 1 to 25 months). CA 15-3 and carcinoembryonic antigen (CEA) were compared in the same breast cancer NED patient population. Elevated CA 15-3 levels (>40 U/ml) were observed in 38 of 1220 patients with benign diseases (3.1%) and in 25 of 350 breast cancer NED patients (7.1%). Elevations of CEA (>5ng/ml) were observed in 23 patients with breast cancer NED (6.5%). Benign diseases that produced significant elevations of CA 15-3 were chronic hepatitis (42.9%), liver cirrhosis (13.3%), sarcoidosis (16.7%), tuberculosis (9.7%), and systemic lupus erythematosous (6.7%).In breast cancer NED, initial elevations of CA 15-3 were observed in 12 of the 297 patients that remained free of disease during the follow-up, and in 13 of the 40 patients that relapsed (4.0% vs. 32.5%, p<0.001). Initial CEA levels were elevated in 16 patients that remained NED and in 7 patients that relapsed (5.3% vs. 17.5%, p<0.001). Serial determinations of CA 15-3 in patients continuously NED showed persistent elevations in 4 cases. Three of these exhibited concomitant benign diseases. In relapsing patients, serial tumor marker determinations showed that elevations of CA 15-3 before any other clinical evidence of recurrence occurred significantly more frequently than elevations of CEA (45% vs. 25%, p<0.001). Overall, two or more serial elevated values of CA 15-3 were observed in 7 cases, and 6 of them (85%) eventually relapsed. Median survival from study entry was 18.3 months in patients with breast cancer NED that had initial elevated CA 15-3, compared to 25+ months in those with negative CA 15-3 (p<0.0001).We conclude that circulating levels of CA 15-3 antigen can be elevated in some patients with nonmalignant diseases, and that serial determinations of CA 15-3 may be useful in the postsurgical follow-up of patients with breast cancer when specific types of benign diseases that may cause elevations of the antigen are excluded. Additionally, CA 15-3 is more sensitive than CEA in the early diagnosis of breast cancer recurrences, and the simultaneous assay of CEA does not add information to that of CA 15-3 alone.     

Axillary versus peripheral blood levels of sialic acid,ferritin, and CEA in patients with breast cancer

Summary Serum levels of total sialic acid, carcinoembryonic antigen (CEA), ferritin, lactate dehydrogenase, and creatine phosphokinase were measured both in tumor drainage blood (axillary vein) and in peripheral blood obtained from 121 breast cancer patients during surgery. No significant differences between mean values in peripheral and tumor draining blood, between cancer patients and healthy controls, or between patients with or without axillary lymph node metastases were found for any of the markers. Both ferritin and CEA levels were higher in axillary and peripheral blood from patients with central breast cancer versus other sites but the difference was significant only for CEA (p < 0.05). CEA levels were significantly higher (p < 0.01) in patients with > 2 cm diameter carcinomas versus T1 stage patients in axillary but not in peripheral blood. When the cephalic vein was clamped before the axillary sample was taken, ferritin showed a significant increase (p < 0.05). We conclude that measurement of sialic acid, CEA, and ferritin in axillary venous blood in breast cancer patients is not of clinical benefit, although further data are needed to clarify whether other advantages can be derived.     

Circulating tumour cells are associated with increased risk of venous thromboembolism in metastatic breast cancer patients

Background:

Cancer is a risk factor for venous thromboembolism (VTE). Circulating tumour cells (CTCs) are an independent predictor of survival in metastatic breast cancer (MBC) patients. The aim of this study was to test the hypothesis that CTCs are associated with the risk of VTE in MBC patients.

Methods:

This retrospective study included 290 MBC patients treated in the MD Anderson Cancer Center from January 2004 to December 2007. Circulating tumour cells were detected and enumerated using the CellSearch system before starting new lines of therapy.

Results:

At a median follow-up of 12.5 months, 25 patients experienced VTE and 53 patients died without experiencing thrombosis. Cumulative incidence of thrombosis at 12 months was 8.5% (95% confidence interval (CI)=5.5%, 12.4%). Patients with CTCs ⩾1 and ⩾5 had a higher incidence of VTE compared with patients with 0 and <5 CTCs (12-month estimate, 11.7 and 11.6% vs 3 and 6.6%; P=0.006 and P=0.076, respectively). In the multivariate model, patients with CTCs⩾1 had a hazard ratio of VTE of 5.29 (95% CI=1.58, 17.7, P=0.007) compared with patients with no CTCs.

Conclusion:

These results suggest that CTCs in MBC patients are associated with increased risk of VTE. These patients should be followed up more closely for the risk of VTE.     

Exploring circulating micro‐RNA in the neoadjuvant treatment of breast cancer

Breast cancer is the most frequently diagnosed malignancy amongst females worldwide. In recent years the management of this disease has transformed considerably, including the administration of chemotherapy in the neoadjuvant setting. Aside from increasing rates of breast conserving surgery and enabling surgery via tumour burden reduction, use of chemotherapy in the neoadjuvant setting allows monitoring of in vivo tumour response to chemotherapeutics. Currently, there is no effective means of identifying chemotherapeutic responders from non‐responders. Whilst some patients achieve complete pathological response (pCR) to chemotherapy, a good prognostic index, a proportion of patients derive little or no benefit, being exposed to the deleterious effects of systemic treatment without any knowledge of whether they will receive benefit. The identification of predictive and prognostic biomarkers could confer multiple benefits in this setting, specifically the individualization of breast cancer management and more effective administration of chemotherapeutics. In addition, biomarkers could potentially expedite the identification of novel chemotherapeutic agents or increase their efficacy. Micro‐RNAs (miRNAs) are small non‐coding RNA molecules. With their tissue‐specific expression, correlation with clinicopathological prognostic indices and known dysregulation in breast cancer, miRNAs have quickly become an important avenue in the search for novel breast cancer biomarkers. We provide a brief history of breast cancer chemotherapeutics and explore the emerging field of circulating (blood‐borne) miRNAs as breast cancer biomarkers for the neoadjuvant treatment of breast cancer. Established molecular markers of breast cancer are outlined, while the potential role of circulating miRNAs as chemotherapeutic response predictors, prognosticators or potential therapeutic targets is discussed.     

Circulating MMP2 and MMP9 in breast cancer -- potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories

Matrix metalloproteinase (MMP) 2 and 9 are involved in cancer invasion and metastasis, and increased levels occur in serum and plasma of breast cancer (BC) patients. It is, however, unclear whether changes in serum levels can be exploited for early detection or classification of patients into different risk/disease categories. In our study, we measured concentration and activity of MMP2/9 in sera of 345 donors classified as low risk (Gail score <1.7), high risk (HR) (Gail score > or =1.7), benign disease or BC. Kruskal-Wallis and Mann-Whitney nonparametric tests showed that total-MMP2 concentration is higher in HR compared to control (p = 0.012), benign (p = 0.001) and cancer (p = 0.007). Active MMP2 (aMMP2) concentration is higher in control than benign and cancer (p < 0.001, respectively). Total and aMMP9 concentrations are higher in cancer than benign (p < 0.001, p = 0.002, respectively). Total-MMP2 and total-MMP9 activities are lower in control than benign (p < 0.001, p = 0.002, respectively) and cancer (p < 0.001, respectively). Total-MMP2 and MMP9 activities are also higher in cancer than benign (p = 0.004, p < 0.001) and HR (p = 0.008, p = 0.007, respectively). These results were not affected by age or inclusion/exclusion of donors with noninvasive cancer or atypical hyperplasia. Linear discriminant analysis revealed that HR donors are characterized by lower total-MMP2 and higher aMMP2. Overall group classification accuracy was 64.5%. Independent validation based on the leave-one-out cross validation approach gave an overall classification of 63%. Our study provides evidence supporting the potential role of serum MMP2/9 as biomarkers for breast disease classification.     

肿瘤患者外周血游离DNA的研究进展

肿瘤患者外周血中存在着游离DNA,其含量明显高出健康人水平,并且这些游离DNA具有肿瘤特征性。定量这些游离DNA并分析其肿瘤特征性(主要介绍微卫星的改变,如杂合性缺失LOH及微卫星不稳定性MSI),对肿瘤的诊断、治疗及预后的评价都具有重要意义。     

Circulating tumor cells in pancreatic cancer patients: Methods of detection and clinical implications

The poor prognosis of pancreatic cancer patients is associated with the frequent and early dissemination of the disease, as well as late detection due to unspecific and late symptoms from the primary tumor. Pancreatic cancers frequently spread to the liver, lung and skeletal system, suggesting that pancreatic tumor cells must be able to intravasate and travel through the circulation to distant organs. Circulating tumor cells (CTCs) are tumor cells that have acquired the ability to enter the circulatory system; this cell population is ultimately responsible for the development of metastases in distant organs. Clinical studies have revealed that the presence of CTCs in blood is correlated with disease progression for other cancers, such as breast, colorectal and prostate cancer. However, as CTCs are extremely rare, both enrichment and sensitive methods of detection are required for their enumeration. This review highlights various enrichment procedures and methods for the detection of CTCs. Furthermore, we systematically review previously reported studies of the clinical relevance of CTC detection in pancreatic cancer patients. There is evidence that the presence of CTCs also correlates with an unfavorable outcome in pancreatic cancer patients. However, technical/methodological issues may explain why some studies only show a trend toward an association between CTC detection and disease progression. Larger studies, as well as characterization of the CTC population, are required to achieve further insight into the clinical implications of CTC detection in pancreatic cancer patients.     

Quantitation of circulating DNA in the serum of breast cancer patients by real-time PCR

The purpose of this study was to quantify the level of serum DNA in different groups of primary breast cancer patients and in healthy controls using real-time quantitative PCR in order to determine whether such measurements have diagnostic or prognostic value. A total of 96 serum samples of patients with primary breast cancer before surgery (with positive or negative lymph nodes and with high or low relapse-free survival) as well as 24 healthy controls were analysed. DNA concentrations in the serum of the patients differed significantly from the concentration of serum DNA in the controls (medians were 221 and 63 ng x ml(-1), respectively, P<0.001 M-W test). However, no statistically significant difference was observed between the patient groups (P=0.87, M-W test). The serum DNA levels were elevated independently of the size of primary tumour or lymph node metastases. The overall survival of patients with serum DNA concentrations >221 ng x ml(-1) was better than patients with serum DNA concentration 相似文献   

miR-148a-3p、miR-128、miR-588在乳腺癌中的表达情况及其与耐药性的关系

目的:了解microRNA在乳腺癌中的表达情况,以及其对肿瘤化疗药物耐药性的影响。方法:获取GEOGSE71142的microRNA表达数据,通过edgeR和热图寻找乳腺癌耐药和药物敏感两组中差异性表达的microRNA。收集我院2012年至2015年100例病理诊断为乳腺癌的患者的癌及癌旁组织。使用qRT-PCR检测microRNA在癌和癌旁中的表达情况以及在MCF-7中的表达情况;应用配对t检验分析microRNA和T、N、M分期之间的关系。使用倾向值匹配模型（PSM）,将患者分为耐药组和非耐药组,使用qRT-PCR检测microRNA的表达情况。使用Logistic回归模型进行多因素分析。按照microRNA的表达情况,进行亚组分析。结果:使用edgeR对GSE71142进行差异性表达分析,共筛选出了1 432个差异性表达的microRNA。应用qRT-PCR,配对样本t检验发现miR-148a-3p（P＜0.05）、miR-128（P＜0.05）、miR-466（P＜0.05）、miR-31-5p（P＜0.05）、miR-588（P＜0.05）在癌和癌旁中差异性表达。卡方检验提示T分期、N分期、Her-2表达以及Cyclin-D1的表达情况与紫杉醇（PTX）耐药性有关（P＜0.05）。PSM匹配后,在PTX耐药及PTX敏感中,qRT-PCR发现miR-148a-3p、miR-128、miR-588呈差异性表达（P＜0.05）。ROC曲线提示miR-148a-3p（AUC:0.864,95%CI:0.737~0.991,P＜0.05）、miR-128（AUC:0.859,95%CI:0.733~0.986,P＜0.05）和miR-588（AUC:0.777,95%CI:0.623~0.930,P＜0.05）。Logistic回归提示miR-148a-3p（OR=18.36,P＜0.05）和miR-128是PTX耐药的保护因素（OR=5.26,P＜0.05）;而miR-588是PTX耐药的危险因素（OR=0.35,P＜0.05）。miR-148a-3p的亚组分析提示其高表达和低表达均与Cyclin-D1的表达有关。结论:miR-148a-3p、miR-128、miR-466、miR-31-5p、miR-588有成为乳腺癌肿瘤标志物的可能;miR-148a-3p、miR-128、miR-588与乳腺癌的PTX耐药性有关;miR-148a-3p、miR-128可以用于判断患者的PTX耐药情况。miR-148a-3p可能通过Cyclin-D1调控PTX耐药性,但需要进一步的分子学机制研究证实。