A MicroRNA Expression Signature In Taxane-anthracycline-Based Neoadjuvant Chemotherapy Response

Zheng, Yi; Li, Shuai; Boohaker, Rebecca J.; Liu, Xinli; Yufen, Zhu; Zhai, Lili; Li, Huilan; Gu, Feng; Fan, Yu; Lang, Ronggang; Liu, Fangfang; Qian, Xiaolong; Xu, Bo; Fu, Li

doi:10.7150/jca.11616

Cited by 22 publications

(26 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, changes in plasma and tumor-based miRNA were not associated with each other as non-tumoral sources such as endothelial-derived miRNAs may have contributed to the pattern of circulating miRNAs in plasma [7, 20]. Zheng et al reported increased miR-125b and miR-141 associated with non-pCR after anthracycline-taxane based chemotherapy in 21 breast cancers [50]. In 246 patients with estrogen-receptor positive breast cancers, higher levels of miR-30 and miR-182 were associated with benefit from adjuvant tamoxifen treatment and longer progression-free survival [38].…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs miR-7 and miR-340 predict response to neoadjuvant chemotherapy in breast cancer

Raychaudhuri

Bronger

Buchner

et al. 2017

Breast Cancer Res Treat

View full text Add to dashboard Cite

Purpose miRNAs have been linked to chemosensitivity of breast cancer cells in-vitro. In patients, however, there is no clinically validated method for predicting chemotherapy response. The aim of this study was to assess whether I) a specific pattern of miRNA expression in pretherapeutic biopsies can predict response to neoadjuvant chemotherapy, and II) differential miRNA expression in residual tumor after completion of chemotherapy allows further prognostic stratification of non-responding patients. Methods Sixty-four patients with newly diagnosed large (≥3cm) or locally advanced primary breast cancers who underwent neoadjuvant anthracycline/taxane-based chemotherapy were included. Relative expression of 10 miRNAs likely to be associated with chemotherapy response (miR-7,-21,-29a,-29b,-34a,-125b,-155,-200c,-340,-451) was determined by quantitative RT-PCR from pretherapeutic biopsies (n=64) and residual invasive tumor after chemotherapy (n=42). Pathologic complete response (pCR) defined by absence of invasive tumor served as reference standard. In addition, miRNA expression was compared with disease-free and overall-survival. Results Nine (14%) of 64 patients achieved pCR. High expression of miR-7 and low expression of miR-340 in pretherapeutic biopsies predicted pCR with a negative-predictive-value of 96% and 97%, respectively (specificity 54% and 57%). The combined profile of miR-7high/miR-340low demonstrated improved specificity of 86% while maintaining a high negative-predictive-value (96%) to identify non-responders. Pretherapeutic expression of miR-200c and miR-155 showed prognostic information and low expression was associated with increased overall survival (115 vs. 90 months, p≤0.03). After chemotherapy, the overall survival of patients with residual invasive tumor was better for those demonstrating low miR-7 or high miR-125b (p=0.01). Conclusions Intratumoral expression of miR-7 and miR-340 prior to neoadjuvant chemotherapy could be used to predict pCR and a profile of miR-7low or miR-340high identified patients unlikely to achieve pCR who might benefit from alternative treatment options including earlier surgery. Our study identifies miRNAs as promising predictive biomarkers, which could aid in optimization of breast cancer management and treatment stratification.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNAs miR-7 and miR-340 predict response to neoadjuvant chemotherapy in breast cancer

Raychaudhuri

Bronger

Buchner

et al. 2017

Breast Cancer Res Treat

View full text Add to dashboard Cite

show abstract

“…For instance, hsa-miR-141 is overexpressed in cisplatin resistant ovarian, gastric and esophageal squamous cancer cells [ 37 – 39 ]. Furthermore, hsa-miR-141 expression was associated with chemoresistance in breast cancer patients receiving neoadjuvant chemotherapy [ 40 ] and was elevated in MDA-MB-231 invasive breast carcinoma cell line [ 41 ]. Members of the hsa-miR-181 family were involved in myeloid differentiation and acute myeloid leukemia [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic control of phospholipase A2 receptor expression in mammary cancer cells

et al. 2015

View full text Add to dashboard Cite

BackgroundIt has recently been proposed that the M-type phospholipase A2 receptor (PLA2R1) acts as a tumour suppressor in certain malignancies including mammary cancer. Considering that DNA methylation is an important regulator of gene transcription during carcinogenesis, in the current study we analyzed the PLA2R1 expression, PLA2R1 promoter methylation, and selected micro RNA (miRNA) levels in normal human mammary epithelial cells (HMEC) and cancer cell lines.MethodsLevels of PLA2R1 and DNA methyltransferases (DNMT) specific mRNA were determined using real-time RT-PCR. Methylation specific-high resolution melting (MS-HRM) analysis was utilized to quantify the methylation degree of selected CpG sites localized in the promoter region of the PLA2R1 gene. Expression of miRNA was tested using miScript Primer Assay system.ResultsNearly complete methylation of the analyzed PLA2R1 promoter region along with PLA2R1 gene silencing was identified in MDA-MB-453 mammary cancer cells. In MCF-7 and BT-474 mammary cancer cell lines, a higher DNA methylation degree and reduced PLA2R1 expression were found in comparison with those in normal HMEC. Synergistic effects of demethylating agent (5-aza-2′-deoxycytidine) and histone deacetylase inhibitor (trichostatin A) on PLA2R1 transcription in MDA-MB-453 cells confirmed the importance of DNA methylation and histone modification in the regulation of the PLA2R1 gene expression in mammary cells. Furthermore, significant positive correlation between the expression of DNMT1 and PLA2R1 gene methylation and negative correlation between the cellular levels of hsa-mir-141, −181b, and -181d-1 and the expression of PLA2R1 were identified in the analyzed cells. Analysis of combined z-score of miR-23b, −154 and -302d demonstrated a strong and significant positive correlation with PLA2R1 expression.ConclusionsOur data indicate that (i) PLA2R1 expression in breast cancer cells is controlled by DNA methylation and histone modifications, (ii) hypermethylation of the PLA2R1 promoter region is associated with up-regulation of DNMT1, and (iii) hsa-miR-23b, −154, and −302d, as well as hsa-miR-141, −181b, and −181d-1 are potential candidates for post-transcriptional regulation of PLA2R1 expression in mammary cancer cells.

show abstract

“…Furthermore, elevated miR-125b levels in circulation may be a marker for early breast cancer detection (7). Clinically, elevated expression of miR-125b is associated with non-pathological complete response in breast cancer patients that received taxane-anthracycline-based neoadjuvant chemotherapy (39). Overall, the present study provides evidence that elevated miR-125b expression predicts a poor prognosis, as well as a poor clinical responsiveness of paclitaxel-based neoadjuvant chemotherapy, and is associated with tumor size and TNM stage in HER2-positive breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Elevated microRNA-125b levels predict a worse prognosis in HER2-positive breast cancer patients

et al. 2016

View full text Add to dashboard Cite

Abstract. Breast cancer, the second most common cancer worldwide, is the leading cause of cancer-associated mortality in women, accounting for ~15% of all cancer-associated mortalities in women. The development, local invasion and metastasis of breast cancer are associated with the dysregulation and mutation of numerous genes and epigenetic mechanisms, including coding RNA and non-coding RNA, such as microRNAs (miRs/miRNAs). Previous studies have shown a dual-faced role of miR-125b in breast cancer. In the present study, a total of 221 paraffin-embedded breast cancer and 49 paraffin-embedded non-cancerous breast tissue samples were collected. In situ hybridization was used to analyze the expression of miR-125b in the breast cancer tissues. Spearman's rank correlation analysis was used to analyze the expression correlation between miR-125b and human epidermal growth factor 2 (HER2). The overall survival estimates over time were calculated using the Kaplan-Meier method with log-rank test. It was found that miR-125b expression was significantly increased in the breast cancer tissues compared with that in the non-cancerous tissues, and high miR-125b expression indicated a poor prognosis in the breast cancer patients. In addition, miR-125b expression was positively correlated with HER2, but not with progesterone receptor and estrogen receptor. Notably, high miR-125b expression was significantly correlated with tumor size and Tumor-Node-Metastasis stage in the HER2-positive breast cancer patients, along with a poor prognosis. The present study provides clinical data to confirm the oncogenic potential of miR-125b, particularly in HER2-positive human breast cancer. Thus, identification of miR-125b may be a potential molecular biomarker for the prediction of clinical outcomes in breast cancer patients, particularly HER2-positive cases that will receive paclitaxel-based neoadjuvant chemotherapy.

show abstract

A MicroRNA Expression Signature In Taxane-anthracycline-Based Neoadjuvant Chemotherapy Response

Cited by 22 publications

References 26 publications

MicroRNAs miR-7 and miR-340 predict response to neoadjuvant chemotherapy in breast cancer

MicroRNAs miR-7 and miR-340 predict response to neoadjuvant chemotherapy in breast cancer

Epigenetic control of phospholipase A2 receptor expression in mammary cancer cells

Elevated microRNA-125b levels predict a worse prognosis in HER2-positive breast cancer patients

Contact Info

Product

Resources

About