Explore the vast range of titles available.

Background: Prostate cancer (PCa) is characterised by great heterogeneity of the disease progression rate. Tumours range from insignificant and not life threatening to high risk for relapse ones. Consequently, a large number of patients undergo unnecessary treatment. miR-145 is a well-documented tumour suppressor and its expression, which is regulated by the p53 pathway, has been found to be decreased in the majority of human malignancies. The aim of our study was to evaluate the clinical utility of miR-145 for the prognostication of PCa. Methods: Total RNA was isolated from 137 prostate tissue specimens obtained from 73 radical prostatectomy-treated PCa patients and 64 transurethral- or open prostatectomy-treated benign prostate hyperplasia (BPH) patients. Following polyadenylation and reverse transcription, miR-145 levels were determined by quantitative real-time PCR assay, using SNORD48 (RNU48) for normalisation purposes. Results: Downregulated miR-145 expression was found in PCa compared with BPH patients. The reduction of miR-145 expression in PCa was correlated with higher Gleason score, advanced clinical stage, larger tumour diameter and higher prostate-specific antigen (PSA) and follow-up PSA levels. In addition, higher risk for biochemical recurrence and significantly shorter disease-free survival (DFS) was found for the PCa patients expressing lower miR-145. Focusing on ‘low- and intermediate-recurrence risk’ PCa patients, miR-145 loss was revealed to be a reliable predictor of biochemical relapse and poor DFS independent from Gleason score, clinical stage, PSA and patients’ age. Conclusion: The loss of the tumour-suppressor miR-145 increases the risk for disease progression and predicts the poor survival of PCa patients.

Background: MicroRNA expression signatures can promote personalised care for non-small cell lung cancer (NSCLC) patients. Our aim was to evaluate the previously unexplored prognostic potential of miR-197, a key oncogenic molecule for NSCLC. Methods: Total RNA isolation ( n =124 NSCLC and n =21 tumour-adjacent normal tissues), was performed using the QIAsymphony SP workstation. The quantity and quality of RNA were assessed by spectrophotometric analysis and an Agilent 2100 bioanalyzer. Polyadenylation and reverse transcription were subsequently carried out. MiR-197 expression levels were measured by qPCR, after quality control (inter-assay CV=7.8%). Internal validation procedures were followed by assigning training and test sets and robust biostatistical analyses were performed, including bootstrap resampling. Results: MiR-197 is associated with larger tumours ( P =0.042) and the squamous cell carcinoma histotype ( P =0.032). Interestingly, after adjusting for important prognostic indicators, miR-197 expression was identified as a novel independent predictor of unfavourable prognosis for NSCLC patients (HR=1.97, 95% CI=1.10–3.38, P =0.013). We also demonstrate that miR-197 retains its prognostic performance in both early-stage I ( P =0.045) and more advanced-stage individuals ( P =0.036). Conclusions: The cost-effective expression analysis of miR-197 could constitute a novel molecular tool for NSCLC management.

The methylation of arginine has been implicated in many cellular processes, such as regulation of transcription, mRNA splicing, RNA metabolism and transport. The enzymes responsible for this modification are the protein arginine methyltransferases. The most abundant methyltransferase in human cells is protein arginine methyltransferase 1. Methylation processes appear to interfere in the emergence of several diseases, including cancer. During our study, we examined the expression pattern of protein arginine methyltransferase 1 gene in colon cancer patients. The emerging results showed that the expression of one of the gene variants is associated with statistical significant probability to clinical and histological parameters, such as nodal status and stage. This is a first attempt to acquire an insight on the possible relation of the expression pattern of protein arginine methyltransferase 1 and colon cancer progression.

Background: Metastatic clear cell renal cell carcinoma (ccRCC) patients have <9% 5-year survival rate, do not respond well to targeted therapy and eventually develop resistance. A better understanding of molecular pathways of RCC metastasis is the basis for the discovery of novel prognostic markers and targeted therapies. Methods: We investigated the biological impact of galectin-1 (Gal-1) in RCC cell lines by migration and invasion assays. Effect of Gal-1 expression on the mitogen-activated protein kinase pathway was assessed by proteome array. Results: Increased expression of Gal-1 increased cell migration while knocking down Gal-1 expression by siRNA resulted in reduced cellular migration ( P <0.001) and invasion ( P <0.05). Gal-1 overexpression increased phosphorylation of Akt, mTOR and p70 kinase. Upon hypoxia and increased HIF-1 α , Gal-1 increased in a dose-dependent manner. We also found miR-22 overexpression resulted in decreased Gal-1 and HIF-1 α . Immunohistochemistry analysis showed that high Gal-1 protein expression was associated with larger size tumor ( P =0.034), grades III/IV tumors ( P <0.001) and shorter disease-free survival ( P =0.0013). Using the Cancer Genome Atlas data set, we found that high Gal-1 mRNA expression was associated with shorter overall survival (41 vs 78 months; P <0.01). Conclusions: Our data suggest Gal-1 mediates migration and invasion through the HIF-1 α –mTOR signaling axis and is a potential prognostic marker and therapeutic target.

Introduction/BackgroundOvarian cancer (OC) is the most common cause of gynecological cancer-related death in developed countries. The absence of evident early symptoms and effective asymptomatic population screening leads to diagnosis in advanced stages for the majority of patients and, thus, to poor prognosis. Consequently, the identification of predictive markers of patients´ treatment outcome could ameliorate disease management. microRNA-34a (miR-34a) is highlighted to exert a tumor suppressive role in several malignancies and is downregulated in numerous cancers. According to TarBase v.8, highthroughput studies have reported the negative correlation of miR-34a with kallikrein-related peptidase 6 (KLK6) expression levels. In the present study, we aimed to investigate the expression profile of miR-34a in ovarian carcinomas and to explore its clinical value in OC patients.MethodologyOvarian cancer specimens and matched adjacent tissues were obtained from St. Savvas Regional Anticancer Oncology Hospital of Athens. Following homogenization, total RNA was extracted using TRI reagent. Thereafter, the RNA was polyadenylated in the 3’-end and first-strand cDNA synthesis was performed by MMLV using an oligo (dT) adapter. A SYBR-Green fluorescent-based qPCR assay was developed to quantify miR-34a, using snoRNA RNU48 as endogenous reference control gene for normalization purposes. Extensive statistical analysis has been conducted to explore the clinical utility of miR-34a levels.ResultsThe expression analysis demonstrated that miR-34a levels are downregulated in ovarian tumors compared to normal epithelium. With regard to clinicopathological characteristics, patients with tumor grade 3 (G3) were highlighted to underexpress miR-34a compared to OC patients with tumor grade 1 (G1) or 2 (G2). Ultimately, no association was observed between FIGO stages and miR-34a expression levels.ConclusionThe tumor-suppressor miR-34a is downregulated in ovarian malignant epithelium and correlated with higher tumor grading, supporting its further evaluation as a potential molecular marker in OC prognosis.DisclosureNothing to disclose

Matrix metalloprotease-9 (MMP-9; 92 kDa type IV collaganase, gelatinase B) is regarded as, important for degradation of the basement membrane and extracellular matrix during cancer invasion and other tissue-remodelling events. In this study we evaluate the prognostic value of MMP-9, by immunoperoxidase staining in a series of 210 breast cancer tissues. The results were quantitated using the HSCORE system, which consider both staining intensity and the percentage of cells stained at given intensities. MMP-9 status was compared with the concentration of cytosolic Cathepsin-D and with other established prognostic factors, in terms of disease free survival and overall survival. The median follow-up period was 62 months. MMP-9 staining was observed primarily in cancer cells, and to a lesser degree in surrounding stromal cells. MMP-9 expression was not detected in normal breast tissue. Levels of MMP-9 expression below the cut-off point were more frequently observed in larger ( P =0.014), invasive ductal histologic ( P =0.037), progesterone receptor (PR)-negative and PR-strong positive tumours ( P < 0.001), as well as samples belonging to patients with stage III-IV disease ( P =0.009) and age 45–55 years ( P =0.011). In univariate analysis, node-negative breast cancer patients with tumors positive for MMP-9 had a considerable reduction in risk for relapse (RR=0.45; P =0.039) or death (RR=0.32; P =0.009). Multivariate analysis indicated that MMP-9 status was an independent favourable predictor of OS (RR=0.47; P =0.034) in node-negative but not in node-positive patients. Our results suggest that MMP-9 may be an independent favourable prognostic factor in node-negative breast cancer patients. The overexpression of MMP-9 in breast cancer may be also used as a marker to subdivide node negative breast cancer patients in order to determine the optimal treatment modality. © 2001 Cancer Research Campaign http://www.bjcancer.com

Background: L-DOPA decarboxylase (DDC) is an enzyme that catalyses, mainly, the decarboxylation of L -DOPA to dopamine and was found to be involved in many malignancies. The aim of this study was to investigate the mRNA expression levels of the DDC gene and to evaluate its clinical utility in tissues with colorectal adenocarcinoma. Methods: Total RNA was isolated from colorectal adenocarcinoma tissues of 95 patients. After having tested RNA quality, we prepared cDNA by reverse transcription. Highly sensitive quantitative real-time PCR method for DDC mRNA quantification was developed using the SYBR Green chemistry. GAPDH served as a housekeeping gene. Relative quantification analysis was performed using the comparative C T method ( 2 - ΔΔC T ) . Results: DDC mRNA expression varied remarkably among colorectal tumours examined in this study. High DDC mRNA expression levels were found in well-differentiated and Dukes’ stage A and B tumours. Kaplan–Meier survival curves showed that patients with DDC -positive tumours have significantly longer disease-free survival ( P =0.009) and overall survival ( P =0.027). In Cox regression analysis of the entire cohort of patients, negative DDC proved to be a significant predictor of reduced disease-free ( P =0.021) and overall survival ( P =0.047). Conclusions: The results of the study suggest that DDC mRNA expression may be regarded as a novel potential tissue biomarker in colorectal adenocarcinoma.

Several members of the human tissue kallikrein-related peptidase (KLK) family are emerging cancer biomarkers. The aim of this study was to analyse the expression of a panel of KLKs in colorectal cancer and to find out if the multiparametric combination of them can increase the accuracy of prediction of patients survival beyond the traditional clinical information. Nine KLKs (KLK5-8, KLK10, KLK11, KLK13-15) were measured using ELISA assays in cytosolic extracts of 122 colon cancer tissues and their nearby normal mucosa, obtained during surgery. The mean levels of almost all KLKs in tumour tissues were significantly different from their counterparts of normal tissue ( P <0.0001). KLK 5, 6, 7, 13, 14 were significantly associated with overall survival in univariate analysis, but after adjusting for age, TNM and differentiation stage, only KLK5 (HR: 1.24 (95% CI: 1.05–1.47)), KLK7 (HR: 1.57 (95% CI: 1.04–2.37)) and KLK14 (HR: 1.43 (95% CI: 1.05–1.94)) remained significant. Addition of a panel of selected KLK markers to clinical parameters gave an increment in AUC of 0.86 beyond the clinical factors at year 1, showing that it can increase the accuracy of prediction of overall survival beyond the traditional clinical information, particularly the short-term (1 year) survival after surgery.