The Challenges and Opportunities of lncRNAs in Ovarian Cancer Research and Clinical Use

[Abstract] Ovarian cancer is one of the most lethal gynecological malignancies worldwide because it tends to be detected late, when the disease has already spread, and prognosis is poor. In this review we aim to highlight the importance of long non-coding RNAs (lncRNAs) in diagnosis, prognosis and treatment choice, to make progress towards increasingly personalized medicine in this malignancy. We review the effects of lncRNAs associated with ovarian cancer in the context of cancer hallmarks. We also discuss the molecular mechanisms by which lncRNAs become involved in cellular physiology; the onset, development and progression of ovarian cancer; and lncRNAs’ regulatory mechanisms at the transcriptional, post-transcriptional and post-translational stages of gene expression. Finally, we compile a series of online resources useful for the study of lncRNAs, especially in the context of ovarian cancer. Future work required in the field is also discussed along with some concluding remarks.This work was funded by Plan Estatal I + D + I by the Instituto de Salud Carlos III (ISCIII, Spain) under grant agreement AES number PI18/01714, cofounded by Fondo Europeo de Desarrollo Regional-FEDER (The European Regional Development Fund-ERDF) “A way of Making Europe,” and by Xunta de Galicia (Consolidación Grupos Referencia Competitiva contract number ED431C 2016-012). M.S.M. was funded by a predoctoral fellowship from FPU-2018 (Spain)Xunta de Galicia; ED431C 2016-01

Evaluation of Plakophilin-3 mRNA as a biomarker for detection of circulating tumor cells in gastrointestinal cancer patients

[Abstract] Background: This study aims to assess Plakophilin-3 (PKP3) as a surrogate biomarker of circulating tumor cells in patients with gastrointestinal cancer. Methods: The primary aim is to estimate the diagnostic accuracy of PKP3 real-time reverse transcriptase-PCR in blood. Receiver operating characteristic curves were constructed. Correlations between the blood PKP3 levels and the clinicopathologic features of the study subjects were analyzed. Logistic regression was used to predict outcomes based on PKP3. Results: Sixty-four patients with gastrointestinal cancer and 23 controls were included. The mean relative PKP3 mRNA expression was 48.45 in cancer patients and 2.8 in controls (P < 0.0001). Comparing the PKP3 levels in patients and controls, the area under the curve was 0.852 (95% confidence interval, 0.76-0.94; P < 0.0001) in receiver operating characteristic analysis. A higher blood level of PKP3 mRNA was associated with a more advanced stage (P = 0.025), pT3-4 tumors (P = 0.028), metastasis (P = 0.021), and residual (R2) disease (P = 0.037). Higher PKP3 mRNA was associated with the risk of cancer progression and death (odds ratio, 3.875; 95% confidence interval, 1.781-8.430; P = 0.001). Conclusions: Increased PKP3 mRNA was detected in the blood of gastrointestinal cancer patients. Significant correlations were found with advanced stage, pT3-4, metastatic disease, and the residual disease status. PKP3 mRNA in blood was associated with the risk of cancer progression and death.Rede Galega de Investigación sobre Cancro Colorrectal; Grant 509025250

Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer

[Abstract] Background. MicroRNAs are aberrantly expressed and correlate with tumourigenesis and the progression of solid tumours. The miR-200 family determines the epithelial phenotype of cancer cells and regulates invasiveness and migration. Thus, we hypothesised that the quantitative detection of the miR-200 family as epithelial-specific microRNAs in the blood could be a useful clinical biomarker for gastric cancer (GC). Methods. We initially validated the expression levels of miR-200a, 200b, 200c and 141 in GC cell lines (n = 2) and blood from healthy controls (n = 19) using real-time quantitative reverse transcription PCR (qRT-PCR). The microarray expression profiles of the miR-200 family in 160 paired samples of non-tumour gastric mucosae and GC were downloaded through ArrayExpress and analysed. MiR-200c was selected for clinical validation. The qRT-PCR prospective assessment of miR-200c was performed using 67 blood samples (52 stage I-IV GC patients and 15 controls); the area under the receiver operating characteristic curve (AUC-ROC) was estimated. The Kaplan-Meier and Breslow-Wilcoxon tests were used to assess the correlation of miR-200c with overall and progression-free survival (OS and PFS). Multivariate analyses were performed using the Cox model. Results. The miR-200c blood expression levels in GC patients were significantly higher than in normal controls (p = 0.018). The AUC-ROC was 0.715 (p = 0.012). The sensitivity, specificity and accuracy rates of 65.4%, 100% and 73.1%, respectively, were observed. The levels of miR-200c in the blood above the cutoff defined by the ROC curve was found in 17.6% of stage I-II GC patients, 20.6% of stage III patients and 67.7% of stage IV patients (p < 0.001). The miR-200c expression levels were not associated with clinical or pathological characteristics or recent surgical procedures. There was a correlation (p = 0.016) with the number of lymph node metastases and the increased expression levels of miR-200c in blood were significantly associated with a poor OS (median OS, 9 vs 24 months; p = 0.016) and PFS (median PFS, 4 vs 11 months; p = 0.044). Multivariate analyses confirmed that the upregulation of miR-200c in the blood was associated with OS (HR = 2.24; p = 0.028) and PFS (HR = 2.27; p = 0.028), independent of clinical covariates. Conclusions. These data suggest that increased miR-200c levels are detected in the blood of gastric cancer patients. MiR-200c has the potential to be a predictor of progression and survival.Instituto de Salud Carlos III; PI061541Xunta de Galicia; PS08/7

Guía gallega de manejo de la trombosis asociada a cáncer. II edición

Esta guía práctica y sencilla, guiará en el diagnóstico y tratamiento de los pacientes con trombosis y cáncer. Pretende reducir la variabilidad en el manejo en la Comunidad Autónoma de Galicia y reducir el impacto negativo que la trombosis presenta en los pacientes con cáncer.This practical and simple guide will guide in the diagnosis and treatment of patients with thrombosis and cancer. It aims to reduce variability in management in the Autonomous Community of Galicia and reduce the negative impact that thrombosis has on cancer patients.Esta guía práctica e sinxela, guiará no diagnóstico e tratamento dos pacientes con trombose e cancro. Pretende reducir a variabilidade no manexo na Comunidade Autónoma de Galicia, e reducir o impacto negativo que a trombose presenta nos pacientes con cancro.Con el Aval de la Sociedad Oncológica de Galicia (SOG) y la Sociedade Galega de Medicina Interna (SOGAMI). Publicado en Barcelona por Bubblegum Communication Services el 25 de ocutubre de 2019. ISBN: 978-84-09-1419-4LEO Pharm