Recent studies posit a role for non-coding RNAs in epithelial ovarian cancer (EOC). Combining small RNA sequencing from 179 human serum samples with a neural network analysis produced a miRNA algorithm for diagnosis of EOC (AUC 0.90; 95% CI: 0.81–0.99). The model significantly outperformed CA125 and functioned well regardless of patient age, histology, or stage. Among 454 patients with various diagnoses, the miRNA neural network had 100% specificity for ovarian cancer. After using 325 samples to adapt the neural network to qPCR measurements, the model was validated using 51 independent clinical samples, with a positive predictive value of 91.3% (95% CI: 73.3–97.6%) and negative predictive value of 78.6% (95% CI: 64.2–88.2%). Finally, biologic relevance was tested using in situ hybridization on 30 pre-metastatic lesions, showing intratumoral concentration of relevant miRNAs. These data suggest circulating miRNAs have potential to develop a non-invasive diagnostic test for ovarian cancer.

MicroRNAs (miRNAs) were hypothesized to be robust and easily measured biomarkers of radiation exposure, which has led to multiple studies in various clinical and experimental scenarios. We sought to identify evolutionary conserved, radiation-induced circulating miRNAs through a multispecies, integrative systematic review and meta-analysis of miRNAs in radiation. The systematic review was registered in the PROSPERO database (ID: 81701). We downloaded a list of studies with the query: (circulating OR plasma OR serum) AND (miRNA or microRNA) AND (radiat* OR radiotherapy OR irradiati*) from MEDLINE (103 studies), EMBASE (364 studies), and Cochrane Database of Systematic Reviews (0 studies). After deleting 116 duplicates, the remaining 351 abstracts were reviewed. Inclusion criteria were experimental study; human, mice, rat or nonhuman primate study; and serum or plasma miRNA expression measured before and after radiation exposure. The screening procedure yielded 62 research studies. After verification, 30 articles contained data on miRNA expression change after irradiation. Thus, we obtained a database of 131 miRNAs from 96 pairwise post-/preirradiation comparisons reporting 2508 fold changes (FCs) of circulating miRNAs. The meta-analysis showed 28 miRNAs with significant radiation-induced change of their expression in the serum. In metaregression analysis, 7 miRNAs-miR-150 (FC = 0.40; 95% confidence interval [CI], 0.35-0.45), miR-29a (FC = 0.87; 95% CI, 0.79-0.96), miR-29b (FC = 0.85; 95% CI, 0.76-0.96), miR-30c (FC = 1.19; 95% CI, 1.09-1.30), miR-200b (FC = 1.34; 95% CI, 1.21-1.48), miR-320a (FC = 1.13; 95% CI, 1.05-1.23), and miR-30a (FC = 1.18; 95% CI, 1.07-1.30)-significantly correlated with either total or fraction dose of radiation. Additionally, miR-150, miR-320a, miR-200b, and miR-30c correlated significantly with time elapsed since irradiation. Circulating miRNAs reflect the impact of ionizing radiation irrespective of the studied species, often in a dose-dependent manner. This makes circulating miRNAs promising biomarkers of radiation exposure.

Background: Senescence is a fundamental biological process implicated in various pathologies, including cancer. Regarding carcinogenesis, senescence signifies, at least in its initial phases, an anti-tumor response that needs to be circumvented for cancer to progress. Micro-RNAs, a subclass of regulatory, non-coding RNAs, participate in senescence regulation. At the subcellular level micro-RNAs, similar to proteins, have been shown to traffic between organelles influencing cellular behavior. The differential function of micro-RNAs relative to their subcellular localization and their role in senescence biology raises concurrentin situanalysis of coding and non-coding gene products in senescent cells as a necessity. However, technical challenges have renderedin situco-detection unfeasible until now.Methods: In the present report we describe a methodology that bypasses these technical limitations achieving for the first time simultaneous detection of both a micro-RNA and a protein in the biological context of cellular senescence, utilizing the new commercially available SenTraGor^TMcompound. The method was applied in a prototypical human non-malignant epithelial model of oncogene-induced senescence that we generated for the purposes of the study. For the characterization of this novel system, we applied a wide range of cellular and molecular techniques, as well as high-throughput analysis of the transcriptome and micro-RNAs.Results: This experimental setting has three advantages that are presented and discussed: i) it covers a “gap” in the molecular carcinogenesis field, as almost all correspondingin vitromodels are fibroblast-based, even though the majority of neoplasms have epithelial origin, ii) it recapitulates the precancerous and cancerous phases of epithelial tumorigenesis within a short time frame under the light of natural selection and iii) it uses as an oncogenic signal, the replication licensing factor CDC6, implicated in both DNA replication and transcription when over-expressed, a characteristic that can be exploited to monitor RNA dynamics.Conclusions: Consequently, we demonstrate that our model is optimal for studying the molecular basis of epithelial carcinogenesis shedding light on the tumor-initiating events. The latter may reveal novel molecular targets with clinical benefit. Besides, since this method can be incorporated in a wide range of low, medium or high-throughput image-based approaches, we expect it to be broadly applicable.

Brief Description: The results demonstrate that the European Organisation for Research and Treatment of Cancer (EORTC) scale provides the best recurrence and progression prediction in comparison with European Association of Urology (EAU) and Club Urologico Espanol de Tratamiento Oncologico (CUETO) risk scores among a mixed population of patients with non–muscle‐invasive bladder who were treated with, or without, Bacillus Calmette‐Guerin (BCG) and without any immediate postoperative chemotherapy. The study highlights the role of tumor diameter and extent in transition prediction.This retrospective cohort analysis of 322 patients with newly diagnosed non–muscle‐invasive bladder cancer (NMIBC) assesses the concordance and accuracy of predicting recurrence and progression by EAU‐recommended tools (EAU risk groups, EORTC, and CUETO). One‐year and five‐year c‐indices ranged from 0.55 to 0.66 for recurrence and from 0.72 to 0.82 for progression. AUCROC of predictions ranged from 0.46 for 1‐year recurrence risk based on CUETO groups, to 0.82 for 1‐year progression risk based on EAU risk groups. Diameter (HR: 1.91; 95% CI: 1.39‐2.61) and tumor extent (HR: 1.21; 95% CI: 1.01‐1.46 for recurrence; HR: 3.1; 95% CI: 1.40‐6.87 for progression) were shown to be significant predictors in multistate analysis. Lower accuracy of prediction was observed for patients treated with BCG maintenance immunotherapy. The EORTC model (overall c‐index c = 0.64; 95% CI: 0.61‐0.68) was superior to the EAU (P = .035; .62; 95% CI: 0.59‐0.66) and CUETO (P < .001; c = 0.53; 95% CI: 0.50‐0.56) models in predicting recurrence. The EORTC model (c = 0.82; 95% CI: 0.77‐0.86) also performed better than CUETO (P = .008; c = 0.73; 95% CI: 0.66‐0.81) but there was no sufficient evidence that it performed better than EAU (P = .572; c = 0.81; 95% CI: 0.77‐0.84) for predicting progression. EORTC and CUETO gave similar predictions for progression in BCG‐treated EAU high‐risk patients (P = .48). We share anonymized individual patient data. In conclusion, despite moderate accuracy, EORTC provided the best recurrence and progression prediction for a mixed population of patients treated with, or without BCG, and without immediate postoperative chemotherapy.

Head and neck squamous cell carcinomas (HNSCCs) contribute to over 300,000 deaths every year worldwide. Although the survival rates have improved in some groups of patients, mostly due to new treatment options and the increasing percentage of human papillomavirus (HPV)-related cancers, local recurrences and second primary tumors remain a great challenge for the clinicians. Presently, there is no biomarker for patient surveillance that could help identify patients with HNSCC that are more likely to experience a relapse or early progression, potentially requiring closer follow-up or salvage treatment. MicoRNAs (miRNAs) are non-coding RNA molecules that posttranscriptionally modulate gene expression. They are highly stable and their level can be measured in biofluids including serum, plasma, and saliva, enabling quick results and allowing for repeated analysis during and after the completion of therapy. This has cemented the role of miRNAs as biomarkers with a huge potential in oncology. Since altered miRNA expression was described in HNSCC and many miRNAs play a role in radio- and chemotherapy resistance, cancer progression, and metastasis, they can be utilized as biomarkers of these phenomena. This review outlines recent discoveries in the field of extracellular miRNA-based biomarkers of HNSCC progression and metastasis, with a special focus on HPV-related cancers and radioresistance.