Transcriptome Profiling of Prostate Cancer, Considering Risk Groups and the TMPRSS2-ERG Molecular Subtype.

Molecular heterogeneity in prostate cancer (PCa) is one of the key reasons underlying the differing likelihoods of recurrence after surgical treatment in individual patients of the same clinical category. In this study, we performed RNA-Seq profiling of 58 localized PCa and 43 locally advanced PCa tissue samples obtained as a result of radical prostatectomy on a cohort of Russian patients. Based on bioinformatics analysis, we examined features of the transcriptome profiles within the high-risk group, including within the most commonly represented molecular subtype, TMPRSS2-ERG.

Lymphatic Dissemination in Prostate Cancer: Features of the Transcriptomic Profile and Prognostic Models.

Radical prostatectomy is the gold standard treatment for prostate cancer (PCa); however, it does not always completely cure PCa, and patients often experience a recurrence of the disease. In addition, the clinical and pathological parameters used to assess the prognosis and choose further tactics for treating a patient are insufficiently informative and need to be supplemented with new markers. In this study, we performed RNA-Seq of PCa tissue samples, aimed at identifying potential prognostic markers at the level of gene expression and miRNAs associated with one of the key signs of cancer aggressiveness-lymphatic dissemination.

Docetaxel Resistance in Castration-Resistant Prostate Cancer: Transcriptomic Determinants and the Effect of Inhibiting Wnt/β-Catenin Signaling by XAV939.

Castration-resistant prostate cancer (CRPC) is a common form of prostate cancer in which docetaxel-based chemotherapy is used as the first line. The present study is devoted to the analysis of transcriptome profiles of tumor cells in the development of resistance to docetaxel as well as to the assessment of the combined effect with the XAV939 tankyrase inhibitor on maintaining the sensitivity of tumor cells to chemotherapy. RNA-Seq was performed for experimental PC3 cell lines as well as for plasma exosome samples from patients with CRPC.

, , , and MicroRNA-503-5p Expression to Forecast Recurrence in -Positive Prostate Cancer.

Following radical surgery, patients may suffer a relapse. It is important to identify such patients so that therapy tactics can be modified appropriately. Existing stratification schemes do not display the probability of recurrence with enough precision since locally advanced prostate cancer (PCa) is classified as high-risk but is not ranked in greater detail.

Dynamic Profiling of Exosomal microRNAs in Blood Plasma of Patients with Castration-Resistant Prostate Cancer.

Prostate cancer is one of the most common and socially significant cancers among men. The aim of this study was to identify significant changes in the expression of exosomal miRNAs associated with an increase in the level of prostate specific antigen in castration-resistant prostate cancer during therapy and to evaluate them as potential prognostic markers for this category of disease. High-throughput miRNA sequencing was performed on 49 blood plasma samples taken from 11 Russian patients with castration-resistant cancer during therapy.

Impact TMPRSS2-ERG Molecular Subtype on Prostate Cancer Recurrence.

Currently, seven molecular subtypes of prostate cancer (PCa) are known, the most common of which being the subtype characterized by the presence of the TMPRSS2-ERG fusion transcript. While there is a considerable amount of work devoted to the influence of this transcript on the prognosis of the disease, data on its role in the progression and prognosis of PCa remain controversial. The present study is devoted to the analysis of the association between the TMPRSS2-ERG transcript and the biochemical recurrence of PCa.

Gene Expression Changes and Associated Pathways Involved in the Progression of Prostate Cancer Advanced Stages.

Prostate cancer (PC) is one of the most common cancers among men worldwide, and advanced PCs, such as locally advanced PC (LAPC) and castration-resistant PC (CRPC), present the greatest challenges in clinical management. Current indicators have limited capacity to predict the disease course; therefore, better prognostic markers are greatly needed. In this study, we performed a bioinformatic analysis of The Cancer Genome Atlas (TCGA) datasets, including RNA-Seq data from the prostate adenocarcinoma (PRAD; = 55) and West Coast Dream Team - metastatic CRPC (WCDT-MCRPC; = 84) projects, to evaluate the transcriptome changes associated with progression-free survival (PFS) for LAPC and CRPC, respectively.

miRNAs expression signature potentially associated with lymphatic dissemination in locally advanced prostate cancer.

Background: Prostate cancer is one of the most common and socially significant cancers among men. The aim of our study was to reveal changes in miRNA expression profiles associated with lymphatic dissemination in prostate cancer and to identify the most prominent miRNAs as potential prognostic markers for future studies.

Methods: High-throughput miRNA sequencing was performed for 44 prostate cancer specimens taken from Russian patients, with and without lymphatic dissemination (N1 - 20 samples; N0 - 24 samples).

Differentially Expressed Genes Associated With Prognosis in Locally Advanced Lymph Node-Negative Prostate Cancer.

Older age is one of the main risk factors for cancer development. The incidence of prostate cancer, as a multifactorial disease, also depends upon demographic factors, race, and genetic predisposition. Prostate cancer most frequently occurs in men over 60 years of age, indicating a clear association between older age and disease onset.

Bioinformatic identification of differentially expressed genes associated with prognosis of locally advanced lymph node-positive prostate cancer.

Prostate cancer (PCa) is one of the primary causes of cancer-related mortality in men worldwide. Patients with locally advanced PCa with metastases in regional lymph nodes are usually marked as a high-risk group. One of the chief concerns for this group is to make an informed decision about the necessity of conducting adjuvant androgen deprivation therapy after radical surgical treatment.

[Suppression of NR0B2 gene in Clear Cell Renal Cell Carcinoma Is Associated with Hypermethylation of Its Promoter].

Clear cell renal cell carcinoma (ccRCC) is a common urologic malignancy. Understanding of the transcriptional regulation of oncogenes and tumor suppressor genes involved is critical for the development of the treatments for renal tumors. Using ccRCC subdivision of the TCGA dataset, we identified NR0B2 encoding orphan nuclear receptor as a tumor suppressor candidate in renal tissue.

[Transcription Factor SAP30 Is Involved in the Activation of NETO2 Gene Expression in Clear Cell Renal Cell Carcinoma].

Clear cell renal cell carcinoma (ccRCC) is a common oncourological disease with a high mortality level. The incidence of this type of cancer is constantly increasing, while molecular mechanisms involved in the disease initiation and progression remain far from being fully understood. A problem of the search for novel markers is crucial for improvement of diagnosis and therapy of ccRCC.

[Overexpression of microRNAs miR-9, -98, and -199 Correlates with the Downregulation of HK2 Expression in Colorectal Cancer].

Glycolysis activation is one of the main features of energy metabolism in cancer cells that is associated with the increase in glycolytic enzyme synthesis, primarily, hexokinases (HKs), in many types of tumors. Conversely, in colorectal cancer (CRC) the decrease in the expression of HK2 gene, which encodes one of the key rate-limiting enzyme of glycolysis, was revealed, thus, the study of the mechanisms of its inhibition in CRC is of particular interest. To search for potential microRNAs, inhibiting the expression of HK2 in CRC, we have performed the analysis of data from "The Cancer Genome Atlas" (TCGA) and five microRNA-mRNA target interaction databases (TargetScan, DIANA microT, mirSVR (miRanda), PicTar, and miRTarBase) using original CrossHub software.

HK3 overexpression associated with epithelial-mesenchymal transition in colorectal cancer.

Background: Colorectal cancer (CRC) is a common cancer worldwide. The main cause of death in CRC includes tumor progression and metastasis. At molecular level, these processes may be triggered by epithelial-mesenchymal transition (EMT) and necessitates specific alterations in cell metabolism.

Upregulation of NETO2 gene in colorectal cancer.

Background: Neuropilin and tolloid-like 2 (NETO2) is a single-pass transmembrane protein that has been shown primarily implicated in neuron-specific processes. Upregulation of NETO2 gene was also detected in several cancer types. In colorectal cancer (CRC), it was associated with tumor progression, invasion, and metastasis, and seems to be involved in epithelial-mesenchymal transition (EMT).

Plasma Level of hsa-miR-619-5p microRNA Is Associated with Prostatic Cancer Dissemination beyond the Capsule.

Profiles of circulating microRNA in the plasma of patients with prostate cancer with pathomorphological stages pT2, pT3, and pT4 are analyzed. The level of circulating microRNA hsa-miR-619-5p is elevated in patients with extracapsular spreading of the tumor, increasing significantly from stage pT2 to stage pT4.

Effect of lentivirus-mediated shRNA inactivation of HK1, HK2, and HK3 genes in colorectal cancer and melanoma cells.

Background: The switch from oxidative phosphorylation to glycolysis in proliferating cancer cells, even under aerobic conditions, has been shown first in 1926 by Otto Warburg. Today this phenomenon is known as the "Warburg effect" and recognized as a hallmark of cancer. The metabolic shift to glycolysis is associated with the alterations in signaling pathways involved in energy metabolism, including glucose uptake and fermentation, and regulation of mitochondrial functions.

Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC molecular pathogenesis is heterogeneous and may be followed by mutations in oncogenes and tumor suppressor genes, chromosomal and microsatellite instability, alternative splicing alterations, hypermethylation of CpG islands, oxidative stress, impairment of different signaling pathways and energy metabolism. In the present work, we have studied the alterations of alternative splicing patterns of genes related to energy metabolism in CRC.

Changes in the Level of Circulating hsa-miR-297 and hsa-miR-19b-3p miRNA Are Associated with Generalization of Prostate Cancer.

We performed diagnostic classification of plasma specimens from patients with non-metastatic and metastatic prostate cancer based on pairs of miRNA that have no individual diagnostic significance. Of 230 miRNA detected in plasma specimens, 3 pairs were diagnostically significant. The miRNA pair hsa-miR-19b-3p and hsa-miR-297 demonstrated highest sensitivity and specificity.

MicroRNA hsa-miR-4674 in Hemolysis-Free Blood Plasma Is Associated with Distant Metastases of Prostatic Cancer.

We analyzed microRNA profile in hemolysis-free blood plasma of patients with prostatic cancer. The metastatic form of prostatic cancer was found to be associated with increased levels of hsa-miR-22-3p, hsa-miR-663a, and hsa-miR-4674 in comparison with non-metastatic form. Common candidate target genes of these microRNA include JUNB, KMT2A, and XPO6.

Plasma Levels of hsa-miR-619-5p and hsa-miR-1184 Differ in Prostatic Benign Hyperplasia and Cancer.

Peripheral blood plasma profiles of circulating microRNA expression were analyzed in patients with prostatic cancer and benign hyperplasia. In prostatic cancer, significant increase in hsa-miR-619-5p and hsa-miR-1184 microRNA expression and significant decrease in hsalet-7b-5p and hsa-let-7c-5p microRNA expression were observed. The role of the relationship between the microRNA expression and the activities and functions of host genes with introns encoding these microRNA is discussed.

Analysis of Plasma microRNA Associated with Hemolysis.

We analyzed the effect of hemolysis on microRNA profi le of blood plasma. It was found that hemolysis of ~0.05% erythrocytes in a sample signifi cantly affected the concentration of 9 microRNA: hsa-miR-486-5p, hsa-miR-16-5p, hsa-miR-451a, hsa-miR-106a-5p, hsa-miR-17-5p, hsa-miR-93-5p, hsa-miR-20a-5p, hsa-miR-107, and hsa-miR-20b-5p.

Profile of microRNA in Blood Plasma of Healthy Humans.

Analysis of the plasma microRNA profile can be used for the diagnosis of various pathological and physiological conditions. Complete microRNA microprofiling is an extremely important task. Here we used microarray analysis allowing measurement of the expression of 2500 microRNA (MirBase, version 20).

[Evaluation of Gene Expression of Hexokinases in Colorectal Cancer with the Use of Bioinformatics Methods].

One of the hallmarks of cancer is the change of energy metabolism, mainly activation of glycolysis that occurs even at early stages of tumorigenesis. The glycolysis activation can be caused by overexpression of hexokinases, primarily HK1 and HK2. Colorectal cancer, which takes the third place in the cancer morbidity and mortality rates worldwide, is believed to be accompanied with overexpression of HK2, which is .