Search

Introduction: MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression and contribute to the development of cancer. They have been shown to be stable in tissue samples and may be promising diagnostic biomarkers for endometrial cancer., Material and Methods: A retrospective cohort study of women diagnosed with endometrial cancer between January 2017 and December 2017 was performed at the Royal Cornwall Hospital. Archived formalin-fixed paraffin-embedded samples were obtained from patients with endometrial cancer and healthy women. MicroRNA was isolated and quantitative real-time polymerase chain reaction was used to detect expression levels of miRNAs., Results: A total of 76 women were included: 36 endometrial cancer patients, 40 healthy controls. A distinct panel of miR-200a, miR-200b, miR-200c, miR-205, and miR-182 showed an area under the curve of 0.958, sensitivity 92%, specificity 89%, positive predictive value of 89% (95% CI 82%-94%) and negative predictive value of 91% (95% CI 85%-96%) in diagnosing endometrial cancer. High miR-182 expression levels were significantly related to high-grade endometrioid tumors compared with low-grade tumors., Conclusions: We demonstrated high diagnostic accuracy of miRNA for detecting endometrial cancer. In addition, miRNA contributed to an improvement in distinguishing between high-grade and low-grade endometrioid tumors., (© 2021 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Introduction: Breast cancer (BC) is the most frequent malignant disease in women worldwide and is therefore challenging for the healthcare system. Early BC detection remains a leading factor that improves overall outcome and disease management. Aside from established screening procedures, there is a constant demand for additional BC detection methods. Routine BC screening via non-invasive liquid biopsy biomarkers is one auspicious approach to either complete or even replace the current state-of-the-art diagnostics. The study explores the diagnostic potential of urinary exosomal microRNAs with specific BC biomarker characteristics to initiate the potential prospective application of non-invasive BC screening as routine practice., Methods: Based on a case-control study (69 BC vs. 40 healthy controls), expression level quantification and subsequent biostatistical computation of 13 urine-derived microRNAs were performed to evaluate their diagnostic relevance in BC., Results: Multilateral statistical assessment determined and repeatedly confirmed a specific panel of four urinary microRNA types (miR-424, miR-423, miR-660, and let7-i) as a highly specific combinatory biomarker tool discriminating BC patients from healthy controls, with 98.6% sensitivity and 100% specificity., Discussion: Urine-based BC diagnosis may be achieved through the analysis of distinct microRNA panels with proven biomarker abilities. Subject to further validation, the implementation of urinary BC detection in routine screening offers a promising non-invasive alternative in women's healthcare.

Background: Deregulated microRNAs (miRNAs) in breast and gynecological cancer might contribute to improve early detection of female malignancies., Objective: Specification of miRNA types in serum and urine as minimally-invasive biomarkers for breast (BC), endometrial (EC) and ovarian cancer (OC)., Methods: In a discovery phase, serum and urine samples from 17 BC, five EC and five OC patients vs. ten healthy controls (CTRL) were analyzed with Agilent human miRNA microarray chip. Selected miRNA types were further investigated by RT-qPCR in serum (31 BC, 13 EC, 15 OC patients, 32 CTRL) and urine (25 BC, 10 EC, 10 OC patients, 30 CTRL) applying two-sample t-tests., Results: Several miRNA biomarker candidates exhibited diagnostic features due to distinctive expression levels (serum: 26; urine: 22). Among these, miR-518b, -4719 and -6757-3p were found specifically deregulated in BC serum. Four, non-entity-specific, novel biomarker candidates with unknown functional roles were identified in urine (miR-3973; -4426; -5089-5p and -6841). RT-qPCR identified miR-484/-23a (all p⩽ 0.001) in serum as potential diagnostic markers for EC and OC while miR-23a may also serve as an endogenous control in BC diagnosis., Conclusions: Promising miRNAs as liquid biopsy-based tools in the detection of BC, EC and OC qualified for external validation in larger cohorts.

Due to the positive association between neoadjuvant chemotherapy (NACT) and the promising early response rates of patients with triple negative breast cancer (TNBC), including probabilities of pathological complete response, NACT is increasingly used in TNBC management. Liquid biopsy‑based biomarkers with the power to diagnose the early response to NACT may support established monitoring tools, which are to a certain extent imprecise and costly. Simple serum‑ or urine‑based analyses of non‑coding RNA (ncRNA) expression may allow for fast, minimally‑invasive testing and timely adjustment of the therapy regimen. The present study investigated breast cancer‑related ncRNAs [microRNA (miR)‑7, ‑9, ‑15a, ‑17, ‑18a, ‑19b, ‑21, ‑30b, ‑222 and ‑320c, PIWI‑interacting RNA‑36743 and GlyCCC2] in triple positive BT‑474 cells and three TNBC cell lines (BT‑20, HS‑578T and MDA‑MB‑231) treated with various chemotherapeutic agents using reverse transcription‑quantitative PCR. Intracellular and secreted microvesicular ncRNA expression levels were analysed using a multivariable statistical regression analysis. Chemotherapy‑driven effects were investigated by analysing cell cycle determinants at the mRNA and protein levels. Serum and urine specimens from 8 patients with TNBC were compared with 10 healthy females using two‑sample t‑tests. Samples from the patients with TNBC were compared at two time points. Chemotherapeutic treatments induced distinct changes in ncRNA expression in TNBC cell lines and the BT‑474 cell line in intra‑ and extracellular compartments. Serum and urine‑based ncRNA expression analysis was able to discriminate between patients with TNBC and controls. Time point comparisons in the urine samples of patients with TNBC revealed a general rise in the level of ncRNA. Serum data suggested a potential association between piR‑36743, miR‑17, ‑19b and ‑30b expression levels and an NACT‑driven complete clinical response. The present study highlighted the potential of ncRNAs as liquid biopsy‑based biomarkers in TNBC chemotherapy treatment. The ncRNAs tested in the present study have been previously investigated for their involvement in BC or TNBC chemotherapy responses; however, these previous studies were restricted to patient tissue or in vitro models. The data from the present study offer novel insight into ncRNA expression in liquid samples from patients with TNBC, and the study serves as an initial step in the evaluation of ncRNAs as diagnostic biomarkers in the monitoring of TNBC therapy.

Although the concept of aerobic glycolysis in cancer was already reported in the 1930s by Otto Warburg, the understanding of metabolic pathways remains challenging especially due to the heterogeneity of cancer. In consideration of four different time points (1, 2, 4, and 7 days of incubation), GC-MS profiling of metabolites was performed on cell extracts and supernatants of breast cancer cell lines (MDA-MB-231, -453, BT-474) with different sub classification and the breast epithelial cell line MCF-10A. To the exclusion of trypsinization, direct methanolic extraction, cell scraping and cell disruption was executed to obtain central metabolites. Major differences in biochemical pathways have been observed in the breast cancer cell lines compared to the breast epithelial cell line, as well as between the breast cancer cell lines themselves. Characteristics of breast cancer subtypes could be correlated to their individual metabolic profiles. PLS-DA revealed the discrimination of breast cancer cell lines from MCF-10A based on elevated amino acid levels. The observed metabolic signatures have great potential as biomarker for breast cancer as well as an improved understanding of subtype specific phenomenons of breast cancer., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Since recent studies revealed the feasibility to detect blood-based microRNAs (miRNAs, miRs) in breast cancer (BC) patients a new field has been opened for circulating miRNAs as potential biomarkers in BC. In this pilot study, we evaluated to our knowledge for the first time whether distinct pattern of urinary miRNAs might be also applicable as innovative biomarkers for BC detection., Methods: Urinary miRNA expression levels of nine BC-related miRNAs (miR-21, miR-34a, miR-125b, miR-155, miR-195, miR-200b, miR-200c, miR-375, miR-451) from 24 untreated, primary BC patients and 24 healthy controls were quantified by realtime-PCR. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy., Results: Significant differences were found in the expression of four BC-associated miRNAs quantified as median miRNA expression levels. Urinary miR-155 levels were significantly higher in BC patients compared to healthy controls (1.49vs.0.25; p < 0.001). In contrast, compared to healthy controls, BC patients exhibited significantly lower urinary expression levels of miR-21 (2.27vs.5.07; p < 0.001), miR-125b (0.71vs.1.62; p < 0.001), and miR-451 (0.02vs.0.59 p = 0.004), respectively. The ROC including all miRNAs as well as the group of the four significant deregulated miRNAs separated BC patients from healthy controls with a very high (area under the receiver operating characteristic curve [AUC] = 0.932) and high accuracy (AUC = 0.887), respectively., Conclusions: We were able to demonstrate for the first time the feasibility to detect distinct BC-dependent urinary miRNA profiles. The expression levels of four urinary miRNAs were specifically altered in our cohort of BC patients compared to healthy controls. This distinct pattern offers the possibility for a specific discrimination between healthy women and primary BC patients. This sustains the potential role of urinary miRNAs as non-invasive innovative urine-based biomarkers for BC detection.