De novo sequencing of circulating microRNAs in locally advanced breast cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Wang Emily
PROVIDER: S-ECPF-GEOD-49035 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been previously reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome. The pre-treatment sera of 42 stage II–III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs.
2013-07-20 | E-GEOD-49035 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been previously reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome.
2013-07-20 | GSE49035 | GEO
Project description:MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome.The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers.More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients.Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.
| S-EPMC3342150 | biostudies-literature
Project description:IntroductionRibociclib is an orally bioavailable cyclin-dependent kinase 4/6 inhibitor. In combination with aromatase inhibitor letrozole, it has approval for treatment of hormone receptor positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. First-line therapy with ribociclib + letrozole significantly improves progression-free survival compared to placebo + letrozole in patients with HR+/HER2- advanced breast cancer. In patients with de novo advanced or metastatic breast cancer, ribociclib was able to provide substantial clinical benefit according to data from the MONALEESA-2 study.Case presentationHere, we report the complete clinical response in a postmenopausal patient with de novo, locally advanced, pulmonary metastatic breast cancer treated with ribociclib + letrozole. Our patient presented an ulcerated breast-consuming tumor with multiple pulmonary metastases. HR+/HER2- breast cancer was confirmed by tumor biopsy. Ki67 expression was 90%. After three months of initial treatment, the tumor-associated ulcerations disappeared, and no measurable pulmonary disease was detectable on CT scan. Treatment was well tolerated, and after dosage reduction due to neutropenia, no further side effects have been documented. At present, complete clinical response remains after 15 months of ongoing treatment.ConclusionThis case report documents an exceptional tumor response of a fast growing, locally advanced, pulmonary metastatic HR+/HER2- de novo breast cancer treated by ribociclib/letrozole combination therapy. Treatment success was long lasting with few side effects. The patient was very satisfied with the treatment and had no specific restrictions in her daily life.
| S-EPMC7383283 | biostudies-literature
Project description:The treatments provided to and survival of patients with recurrent vs de novo stage IV advanced breast, lung, and colorectal cancer may differ but have not been well studied. Using population-based data from the Cancer Research Network for 4510 patients with advanced breast, lung, or colorectal cancer, we matched recurrent/de novo patients on demographic factors. We found longer survival for recurrent vs de novo lung cancer (182 matched pairs); no significant difference for colorectal cancer (332 matched pairs); and shorter survival for recurrent vs de novo breast cancer (219 matched pairs). Compared with recurrent cases, chemotherapy use and radiation therapy use were more common among de novo cases. Differences in treatment and survival between recurrent and de novo advanced cancer patients could inform prognostic estimates and clinical trial design.
| S-EPMC6024888 | biostudies-literature
Project description:miRNAs are an important class of small non-coding RNAs, which play a versatile role in gene regulation at the post-transcriptional level. Expression of miRNAs is often deregulated in human cancers. We analyzed small RNA massive parallel sequencing data from 50 locally advanced breast cancers aiming to identify novel breast cancer related miRNAs. We successfully predicted 10 novel miRNAs, out of which 2 (hsa-miR-nov3 and hsa-miR-nov7) were recurrent. Applying high sensitivity qPCR, we detected these two microRNAs in 206 and 214 out of 223 patients in the study from which the initial cohort of 50 samples were drawn. We found hsa-miR-nov3 and hsa-miR-nov7 both to be overexpressed in tumor versus normal breast tissue in a separate set of 13 patients (p = 0.009 and p = 0.016, respectively) from whom both tumor tissue and normal tissue were available. We observed hsa-miR-nov3 to be expressed at higher levels in ER-positive compared to ER-negative tumors (p = 0.037). Further stratifications revealed particularly low levels in the her2-like and basal-like cancers compared to other subtypes (p = 0.009 and 0.040, respectively). We predicted target genes for the 2 microRNAs and identified inversely correlated genes in mRNA expression array data available from 203 out of the 223 patients. Applying the KEGG and GO annotations to target genes revealed pathways essential to cell development, communication and homeostasis. Although a weak association between high expression levels of hsa-miR-nov7 and poor survival was observed, this did not reach statistical significance. hsa-miR-nov3 expression levels had no impact on patient survival.
| S-EPMC7162276 | biostudies-literature
Project description:ObjectivesPreoperative chemotherapy produces tumor shrinkage in most patients with locally advanced breast cancer, including some pathological complete responses (pCRs). We attempted this using a much less toxic sequential regimen, given with concurrent bevacizumab.MethodsPatients with locally advanced breast cancer received 3 intravenous doses each of preoperative sequential liposome encapsulated doxorubicin 25 mg/m2, paclitaxel 175 mg/m2, and cyclophosphamide 600 mg/m2, with concurrent bevacizumab every 2 weeks without growth factor support.ResultsBetween March 2008 and December 2009, 32 patients received treatment. There was no cardiotoxicity, and other toxicity was mild (no grade 4 or 5 toxicity). No long-term toxicity, including cardiotoxicity, has been observed. Every patient had ≥30% reduction in tumor size; 9 of 31 patients who completed chemotherapy had pCR at operation. Seven years later, 22 of 32 patients remain free of recurrence and 27 of 32 are alive.ConclusionsThe preoperative chemotherapy used appears to be comparably effective, but much less toxic than that used in most conventional regimens and should be studied further. Concurrent treatment with bevacizumab (reported separately) did not provide any additional benefit.
| S-EPMC8787856 | biostudies-literature
Project description:The treatment of patients with breast cancer continues to evolve, with cytotoxic chemotherapy, endocrine therapy, and molecular targeted therapies representing the backbones of modern systemic breast cancer treatment. As we learn better to understand the biology of breast cancer cells, therapies to target specific pathways continue to be developed with the goal of expanding available effective therapy in specific populations. Several targeted drugs with different molecular pathways have achieved approval for metastatic breast cancer, but for early breast cancer trastuzumab is the only one that is currently approved in combination with chemotherapy for adjuvant or neoadjuvant treatment in women with HER2-positive breast cancer. Lapatinib and bevacizumab are both approved for the treatment of metastatic breast cancer and are now investigated in phase III clinical trials testing their effectiveness in the treatment of early breast cancer. In this publication, we review the current status in the treatment of early and locally advanced breast cancer with molecular targeted therapies that are currently approved or in advanced clinical development.
| S-EPMC2931052 | biostudies-other
Project description:AimsRisk stratification in patients with advanced chronic heart failure (HF) is an unmet need. Circulating microRNA (miRNA) levels have been proposed as diagnostic and prognostic biomarkers in several diseases including HF. The aims of the present study were to characterize HF-specific miRNA expression profiles and to identify miRNAs with prognostic value in HF patients.Methods and resultsWe performed a global miRNome analysis using next-generation sequencing in the plasma of 30 advanced chronic HF patients and of matched healthy controls. A small subset of miRNAs was validated by real-time PCR (P < 0.0008). Pearson's correlation analysis was computed between miRNA expression levels and common HF markers. Multivariate prediction models were exploited to evaluate miRNA profiles' prognostic role. Thirty-two miRNAs were found to be dysregulated between the two groups. Six miRNAs (miR-210-3p, miR-22-5p, miR-22-3p, miR-21-3p, miR-339-3p, and miR-125a-5p) significantly correlated with HF biomarkers, among which N-terminal prohormone of brain natriuretic peptide. Inside the cohort of advanced HF population, we identified three miRNAs (miR-125a-5p, miR-10b-5p, and miR-9-5p) altered in HF patients experiencing the primary endpoint of cardiac death, heart transplantation, or mechanical circulatory support implantation when compared with those without clinical events. The three miRNAs added substantial prognostic power to Barcelona Bio-HF score, a multiparametric and validated risk stratification tool for HF (from area under the curve = 0.72 to area under the curve = 0.82).ConclusionsThis discovery study has characterized, for the first time, the advanced chronic HF-specific miRNA expression pattern. We identified a few miRNAs able to improve the prognostic stratification of HF patients based on common clinical and laboratory values. Further studies are needed to validate our results in larger populations.
| S-EPMC8318428 | biostudies-literature
Project description: Not available
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