Dabei Tang

Overexpressions of MicroRNA-9 and MicroRNA-200c in Human Breast Cancers Are Associated with Lymph Node Metastasis

PURPOSE The aim of this study was to investigate the relationship between the expressions of microRNA-9 (miR-9) and microRNA-200c (miR-200c) in human breast cancers and clinicopathological features. METHODS We investigated the expressions of miR-9 and miR-200c in 68 patients with breast cancers using the quantitative reverse transcription-polymerase chain reaction method, and assessed the E-cadherin status using the immunohistochemistry method. RESULTS The relative expression levels of miR-9 and miR-200c in breast cancer patients with lymph node metastasis were higher than that of patients without lymph node metastasis. The expression of miR-9 correlated inversely with E-cadherin expression. CONCLUSIONS The results showed that higher expressions of miR-9 and miR-200c in human breast cancers were associated with lymph node metastasis. This study indicated that the elevation of miR-9 and miR-200c in human breast cancers can induce an invasive phenotype and may serve as a molecular diagnostic marker for patients with breast cancer.

The expression and clinical significance of microRNA-1258 and heparanase in human breast cancer

OBJECTIVES To investigate the expression profile of miR-1258 and heparanase (HPSE) in breast cancer and to assess their clinicopathological significance. DESIGN AND METHODS The expression levels of miR-1258 and HPSE were analyzed in normal, benign and malignant breast tissues. Their serum levels were evaluated in healthy women and in patients with benign and malignant breast disease. We studied the correlation between the expression of miR-1258 and HPSE and the clinical features presented by the patients. RESULTS MiR-1258 was down-regulated and HPSE was up-regulated in breast cancer, with a significant inverse correlation. A reduced miR-1258 expression and an elevated HPSE expression were associated with the lymph node status, late clinical stages, a short overall survival and a short relapse-free survival. In frozen fresh tissue samples, the miR-1258 levels in breast cancer with lymph node metastasis were significantly lower than that of breast cancer without lymph node metastasis and benign disease (BD). In contrast, the HPSE levels in breast cancer with lymph node metastasis were the highest. In serum samples, the miR-1258 levels in metastatic breast cancer (M1) were lower than that of primary breast cancer (M0) and BD. However, serum HPSE levels of M1 patients were significantly higher than that of M0 patients and BD patients. CONCLUSIONS MiR-1258 may play an important role in breast cancer development and progression by regulating the expression of HPSE, and they might be potential prognostic biomarkers for breast cancer.

miRNA-24-3p promotes cell proliferation and inhibits apoptosis in human breast cancer by targeting p27Kip1

MicroRNAs (miRNAs) are often aberrantly expressed in breast cancer and are postulated to play a role in its initiation and progression. In the present study, we found that the expression level of miR-24-3p was upregulated in breast cancer in comparison with the level in adjacent normal tissues. Overexpression of miR-24-3p was able to promote cell proliferation and inhibit cell apoptosis in MDA-MB-435 and MDA-MB-468 cells. With the bioinformatic method, we further identified that p27Kip1 is a direct target of miR-24-3p, and its protein level was negatively regulated by miR-24-3p. Therefore, the data reported here demonstrate that miR-24-3p is an important regulator in breast cancer, and imply that the miR-24-3p/p27Kip1 axis has potential as a therapeutic target for breast cancer.

Indications of Clinical and Genetic Predictors for Aromatase Inhibitors Related Musculoskeletal Adverse Events in Chinese Han Women with Breast Cancer

Background Women with breast cancer treated with aromatase inhibitors (AIs) may experience musculoskeletal symptoms that lead to discontinuation of effective therapy. The purpose of the current study is to evaluate the clinical and genetic predictors for AIs-related musculoskeletal adverse events(MS-AEs). Methodology and Principal Findings We recruited 436 postmenopausal Chinese Han women receiving adjuvant AIs therapy for early-stage hormone-sensitive breast cancer. Patients completed a self-administered questionnaire assessing the presence of musculoskeletal symptoms that started or worsened after initiating AIs. 27 single nucleotide polymorphisms (SNP) of ESR1, ESR2 and PGR were analyzed by Sequenom MassARRAY assays and /or PCR-based TaqMan assays.Of the 436 enrolled women, 206 cases experienced musculoskeletal symptoms.Patients who received taxane chemotherapy were more than two times more likely than other patients to have AIs-related MS-AEs. Genetic assay had showed that only two ESR1 SNPs, rs2234693 and rs9340799 were associated with AIs-related MS-AEs.TT genotype and the T allele in rs2234693 was statistically significantly lower in AIs-Related MS-AEs group than controls (P = 0.001; P = 9.49E-7). The frequency of AA genotype and the A allele in rs9340799 was higher (P = 2.20E-5; P = 3.09E-4). Conclusions and Significance Our results suggested that prior taxane-based chemotherapy was the clinical predictor, while rs2234693 and rs9340799 were the genetic predictors for AIs-related MS-AEs.

Immunological Therapies Can Relieve Aromatase Inhibitor-Related Joint Symptoms in Breast Cancer Survivors

Objectives:Aromatase inhibitors can cause joint symptoms. The purpose of this pilot study was to evaluate the feasibility of immunologic therapies for this kind of joint symptoms. Methods:A total of 16 postmenopausal women with stage I–III breast cancer with joint symptoms related to Aromatase inhibitors were enrolled. They received immunologic therapies of thymosin &agr;1 1.6 mg, twice a week for 4 weeks. Outcome measures included the Brief Pain Inventory-Short Form, Western Ontario and McMaster Universities Osteoarthritis index, and the Functional Assessment of Cancer Therapy-General quality of life measure. Interferon-gamma and interleukin-4 were determined to evaluate immunomodulatory activity. Paired Samples Test and linear regression analysis were used to statistics the outcome measures. Results:From baseline to the end of treatment, patients reported improvement in the mean Brief Pain Inventory-Short Form worst pain scores (5.7–3.4, P < 0.001), pain severity (3.9–2.9, P = 0.01), and pain-related functional interference (4.2–1.8, P < 0.001), as well as the Western Ontario and McMaster Universities Osteoarthritis function subscale and Functional Assessment of Cancer Therapy-General physical well-being (P < 0.001 and P < 0.001, respectively). No adverse events were reported. The mean serum concentrations for secretion of interferon-gamma were significantly lower (P < 0.001); serum concentrations of interleukin 4 were higher (P = 0.02). Conclusion:Immunologic therapies could play a role in reducing Aromatase inhibitor- related joint symptoms in breast cancer survivors and affecting the immune system in powerful ways. The improvements of immune system were associated with aromatase inhibitor-related joint symptoms.

RANKL and OPG Polymorphisms Are Associated with Aromatase Inhibitor-Related Musculoskeletal Adverse Events in Chinese Han Breast Cancer Patients

Background Breast cancer patients treated with aromatase inhibitors (AIs) may experience musculoskeletal adverse events (MS-AEs). Several studies have confirmed that the RANKL/RANK/OPG signaling pathway plays a dominant role in bone health. Therefore, this study aimed to analyze the relationship between the serum levels of RANKL, OPG and their SNPs (single nucleotide polymorphisms) with AI-related MS-AEs. Methodology and Principal Findings Patients with early stage, hormone-sensitive breast cancer who were receiving AI therapy were enrolled. We included 208 cases with AI-related MS-AEs and 212 without (controls). The levels of estradiol, bone-turnover markers, multiple inflammatory cytokines, RANKL,OPG and lumbar spine BMD were measured, and questionnaires were completed. We analyzed 29 SNPs of RANKL, RANK and OPG using Sequenom MassARRAY assays and PCR-based TaqMan assays. The levels of bone-turnover markers and RANKL and the ratio of RANKL/OPG were higher in patients with AI-related MS-AEs than controls (all p < 0.05). A genetic assay showed that the RANKL SNP rs7984870 and OPG SNP rs2073618 were associated with AI-related MS-AEs. In patients with AI-related MS-AEs, rs7984870 CC and rs2073618 CC were risk genotypes. Carriers of the rs7984870 CC genotype were more likely to have a higher RANKL level and RANKL/OPG ratio than carriers of the GG genotype, and carriers of the rs2073618 CC genotype were more likely to have a lower OPG level and a higher RANKL/OPG ratio than carriers of the GG genotype (all p < 0.05). Moreover, risk genotypes were associated with higher levels of serum CTX and PINP and a lower lumbar spine BMD (all p < 0.05). Conclusions and Significance In conclusion, the RANKL and OPG risk genotypes synergize to negatively impact bone health and predispose breast cancer patients to AI-related MS-AEs.