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Whole blood microRNAs as potential biomarkers in post-operative early breast cancer patients.

ABSTRACT: BACKGROUND:microRNAs (miRNAs) are considered promising cancer biomarkers, showing high reliability, sensitivity and stability. Our study aimed to identify associations between whole blood miRNA profiles, presence of circulating tumor cells (CTCs) and clinical outcome in post-operative early breast cancer patients (EBC) to assess the utility of miRNAs as prognostic markers in this setting. METHOD:A total of 48 post-operative patients, recruited in frame of the SUCCESS A trial, were included in this retrospective study and tested with a panel of 8 miRNAs (miR-10b, -19a, -?21, -?22, -20a, -?127, -?155, -200b). Additional 17 female healthy donors with no previous history of cancer were included in the study as negative controls. Blood samples were collected at different time points (pre-adjuvant therapy, post-adjuvant therapy, 2 years follow up), total RNA was extracted and the relative concentration of each miRNA was measured by quantitative PCR and compared in patients stratified on blood collection time or CTC detection. Furthermore, we compared miRNA profiles of patients, for each time point separately, and healthy donors. CTCs were visualized and quantified with immunocytochemistry analysis. Data were analyzed using non-parametric statistical tests. RESULTS:In our experimental system, miR-19a, miR-22 and miR-127 showed the most promising results, differentiating patients at different time points and from healthy controls, while miR-20a, miR-21 and miR-200b did not show any difference among the different groups. miR-10b and miR-155 were never detectable in our experimental system. With respect to patients' clinical characteristics, we found a significant correlation between miR-200b and lymph node status and between miR-20a and tumor type. Furthermore, miR-127 correlated with the presence of CTCs. Finally, we found a borderline significance between Progression Free Survival and miR-19a levels. CONCLUSIONS:This pilot study suggests that profiling whole blood miRNAs could help to better stratify post-operative EBC patients without any sign of metastasis to prevent later relapse or metastatic events.

SUBMITTER: Alunni-Fabbroni M

PROVIDER: S-EPMC5802058 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Whole blood microRNAs as potential biomarkers in post-operative early breast cancer patients.

Alunni-Fabbroni Marianna M Majunke Leonie L Trapp Elisabeth K EK Tzschaschel Marie M Mahner Sven S Fasching Peter A PA Fehm Tanja T Schneeweiss Andreas A Beck Thomas T Lorenz Ralf R Friedl Thomas W P TWP Janni Wolfgang W Rack Brigitte B

BMC cancer 20180206 1

<h4>Background</h4>microRNAs (miRNAs) are considered promising cancer biomarkers, showing high reliability, sensitivity and stability. Our study aimed to identify associations between whole blood miRNA profiles, presence of circulating tumor cells (CTCs) and clinical outcome in post-operative early breast cancer patients (EBC) to assess the utility of miRNAs as prognostic markers in this setting.<h4>Method</h4>A total of 48 post-operative patients, recruited in frame of the SUCCESS A trial, were ...[more]

PMID: 29409452

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Project description:BackgroundPatients undergoing video-assisted thoracoscopic surgery (VATS) have a lower risk of thrombosis compared to those undergoing open thoracotomy (OT) which may be due to several post-operative factors such as early mobilisation, shorter hospital stays, lower transfusion rates and lower risk of infections. Whether the higher thrombotic risk after OT is also linked to a peri-operative hypercoagulable state is a matter of debate. We therefore conducted a case-control study to compare peri-operative coagulation profiles in patients with primary lung cancer undergoing VATS vs OT.Materials and methodsAll consecutive patients undergoing VATS or OT for primary lung cancer at the Department of Thoracic Surgery of Padua University Hospital, Italy, between February and June 2018 were enrolled. Each patient provided a venous blood sample at least 30 min prior to surgical incision (T0) and 4±1 days after surgery (T1). Peri-operative coagulation profiles were assessed via traditional, viscoelastic whole blood (ROTEM® [Instrumentation Laboratory-Werfen]) and impedance aggregometry (Multiplate® Analyser [Roche Diagnostics]) tests.ResultsWe enrolled 65 patients (males 43, females 22; mean age 65±13 years) of whom 35 (54%) underwent VATS and 30 (46%) underwent OT. Compared to healthy controls, the surgical group (VATS and OT patients) had a significantly shorter clot formation time and higher alpha angle and maximum clot firmness values, as well as increased mean platelet function. In the post-operative period, patients who underwent OT had a significantly shorter clot formation time, higher alpha angle and maximum clot firmness values and higher mean platelet function vs VATS patients.DiscussionWhole blood ROTEM® profiles and Multiplate® aggregometry identified a more hypercoagulable post-operative state in patients who underwent OT than in those who underwent VATS. Larger studies are warranted to confirm our results and ascertain whether the observed hypercoagulability might promote post-operative thrombosis.

Project description:MicroRNA (miRNA or miR) is stably present in plasma. It has been reported that miRNA could be used for detecting cancer. Circulating miRNAs are being increasingly recognized as powerful biomarkers in a number of different pathologies, including in breast cancer. The aim of the current study was to establish and validate miRNA sets that are useful for the early diagnosis of breast cancer. Specifically, the current study intended to determine whether miRNA biomarkers were tumor-specific and to statistically verify whether circulating miRNA analysis could be used for breast cancer diagnosis. In the present study, a total of nine candidate miRNA biomarkers were selected by examining reference miRNAs associated with the generation and progression of breast cancer to identify novel miRNAs that could be used to detect early breast cancer. A total of 226 plasma samples from patients with breast cancer were used. In addition, 146 plasma healthy samples were used as non-cancer controls. These samples were divided into training and validation cohorts. The training cohort was used to identify a combination of miRNA that could detect breast cancer. The validation cohort was used to validate this combination of miRNA. Total RNAs were isolated from collected samples. A total of 9 miRNAs were quantified using reverse-transcription quantitative PCR. A total of nine candidate miRNA expression levels were compared between patients with breast cancer and healthy controls. It was indicated that combinations of two or more of the nine miRNAs could detect breast cancer with higher accuracy than the use of a single biomarker. As a representative example, combinations of four miRNAs (miR-1246+miR-206+miR-24+miR-373) of the nine miRNAs had a sensitivity of 98%, a specificity of 96% and an accuracy of 97% for breast cancer detection in the validation cohort. The results of the present study suggest that multiple miRNAs could be used as potential biomarkers for early diagnosis of breast cancer. These biomarkers are expected to overcome limitations of mammography when used as an auxiliary diagnosis of mammography.

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Whole blood microRNAs as potential biomarkers in post-operative early breast cancer patients.

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Whole blood microRNAs as potential biomarkers in post-operative early breast cancer patients.

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