Testing the accuracy of a four serum microRNA panel for the detection of primary bladder cancer: a discovery and validation study.

BACKGROUND: Bladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumour types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC. METHODS: In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively. RESULTS: Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 - 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05). CONCLUSION: The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening.

Early detection and timely intervention can lead to a better prognosis of bladder cancer.This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary bladder cancer.

The value of a panel of circulating microRNAs in screening prostate cancer.

Background: Prostate cancer (PCa) remains a worldwide public health problem that poses a serious threat to the health of men worldwide. Many studies have found that microRNA (miRNA) in serum has the potential to be a biomarker for cancer screening. Our study was conducted to investigate the value of serum miRNAs in PCa screening. Methods: We selected 12 miRNAs from past studies for its association with PCa. We checked the expression levels of these miRNAs in the serum of 112 PCa patients and 112 healthy controls in a two-stage experiment. We plotted the receiver operating characteristic curve of miRNAs in the validation stage and constructed a four-miRNA panel with the highest diagnostic value using stepwise logistic regression. We also predicted the target genes with these four miRNAs through online databases and performed Gene Ontology functional annotation and pathway analysis. Results: The results showed that six miRNAs (miR-429, miR-10a-5p, miR-183-5p, miR-181a-5p, miR-1231, miR-129-5p) were abnormally expressed in the serum of PCa patients. We used four of these miRNAs including miR-1231, miR-10a-5p, miR-429 and miR-129-5p to construct a combination of miRNAs with high specificity and sensitivity in screening PCa (area under the curve =0.878). Bioinformatics analysis showed that the genes targeted by these miRNAs can be linked to the development of PCa. Conclusions: Our study detected and identified a set of miRNAs that serves as screening marker for PCa, which may assist in early diagnosis and treatment of PCa.

Profiling of Serum miRNAs Constructs a Diagnostic 3-miRNA Panel for Clear-Cell Renal Cell Carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) carries significant morbidity and mortality globally with an increasing incidence per year predominantly represented by clear-cell renal cell carcinoma (ccRCC) which accounts for 70-80% of all RCC cases. MicroRNAs(miRNAs) implicate tumor development and progression in epigenetic mechanisms and available profiling of serum miRNAs potentiate them as diagnostic markers for various cancers. MATERIALS AND METHODS: A total of 108 ccRCC patients and 112 normal controls were enrolled. A 3-stage experiment was conducted to identify differentially expressed serum miRNAs in ccRCC and establish a diagnostic miRNAs panel. Additionally, bioinformatic analysis was employed to predict selected miRNAs' target genes, preform functional annotation and explore the roles in ccRCC. RESULTS: MiR-429, miR-10a-5p, miR-154-5p were found to be up-regulated miRNAs. Inversely, miR-27a-3p and miR-221-3p were found to be down-regulated miRNAs. These 5 miRNAs were selected to construct diagnostic panel by backward stepwise logistic regression analysis and ultimately a 3-miRNA panel (miR-429, miR-10a-5p and miR-27a-3p) was established [area under the curve (AUC) = 0.897, sensitivity = 85.0%, specificity = 83.3%]. CONCLUSION: The panel of 3-miRNA holds promise as a novel, convenient, and noninvasive diagnostic method for early detection of ccRCC.

Bladder cancer diagnosis with a four-miRNA panel in serum.

Background: Bladder cancer is one of the most prevalent malignancies. Due to the disadvantage of existing bladder cancer diagnostic tools, miRNAs hold promise as new diagnostic markers. Materials & methods: A total of 224 participants were involved in this three-cohort trial. A total of 15 candidate miRNAs were selected, and miRNAs with diagnostic ability were screened out with quantitative reverse transcription PCR. Diagnostic capability was ascertained by the receiver operating characteristic curve and area under the curve. Bioinformatics analysis was constructed for target gene prediction and functional annotation. Results: Six candidate miRNAs showed significantly different expression between bladder cancer patients and normal controls, and the final diagnostic panel comprised miR-181b-5p, miR-183-5p, miR-199-5p and miR-221-3p. Conclusion: This four-miRNA panel could represent a stable biomarker for bladder cancer diagnosis.

Bladder cancer is one of the most prevalent malignancies. Due to the disadvantage of existing bladder cancer diagnostic tools, miRNAs hold promise as new diagnostic markers. After an experiment composed of 224 participants, the authors screened out six candidate miRNAs that may contribute to diagnosing bladder cancer. The authors also repeatedly verified the reliability of candidate miRNAs. Finally, a combination of multiple miRNAs, consisting of miR-181b-5p, miR-183-5p, miR-199-5p, and miR-221-3p, was better and more reliable in predicting bladder cancer occurrence.

A Four-MicroRNA Panel in Serum as a Potential Biomarker for Screening Renal Cell Carcinoma.

Background: Renal cell carcinoma (RCC) has been a major health problem and is one of the most malignant tumors around the world. Serum microRNA (miRNA) profiles previously have been reported as non-invasive biomarkers in cancer screening. The aim of this study was to explore serum miRNAs as potential biomarkers for screening RCC. Methods: A three-phase study was conducted to explore serum miRNAs as potential biomarkers for screening RCC. In the screening phase, 12 candidate miRNAs related to RCC were selected for further study by the ENCORI database with 517 RCC patients and 71 NCs. A total of 220 participants [108 RCC patients and 112 normal controls (NCs)] were enrolled for training and validation. The dysregulated candidate miRNAs were further confirmed with 30 RCC patients and 30 NCs in the training phase and with 78 RCC patients and 82 NCs in the validation phase. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used for assessing the diagnostic value of miRNAs. Bioinformatic analysis and survival analysis were also included in our study. Results: Compared to NCs, six miRNAs (miR-18a-5p, miR-138-5p, miR-141-3p, miR-181b-5p, miR-200a-3p, and miR-363-3p) in serum were significantly dysregulated in RCC patients. A four-miRNA panel was built by combining these candidate miRNAs to improve the diagnostic value with AUC = 0.908. ABCG1 and RNASET2, considered potential target genes of the four-miRNA panel, may play a significant role in the development of RCC. Conclusion: A four-miRNA panel in serum was identified for RCC screening in our study. The four--miRNA panel has a great potential to be a non-invasive biomarker for RCC screening.

A four-microRNA panel in serum may serve as potential biomarker for renal cell carcinoma diagnosis.

Background: Renal cell carcinoma (RCC) is one out of the most universal malignant tumors globally, and its incidence is increasing annually. MicroRNA (miRNA) in serum could be considered as a non-invasive detecting biomarker for RCC diagnosis. Method: A total of 224 participants (112 RCC patients (RCCs) and 112 normal controls (NCs)) were enrolled in the three-phrase study. Reverse transcription quantitative PCR (RT-qPCR) was applied to reveal the miRNA expression levels in RCCs and NCs. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were utilized to predict the diagnostic ability of serum miRNAs for RCC. Bioinformatic analysis and survival analysis were also included in our study. Results: Compared to NCs, the expression degree of miR-155-5p, miR-224-5p in serum was significantly upregulated in RCC patients, and miR-1-3p, miR-124-3p, miR-129-5p, and miR-200b-3p were downregulated. A four-miRNA panel was construed, and the AUC of the panel was 0.903 (95% CI: 0.847-0.944; p < 0.001; sensitivity = 75.61%, specificity = 93.67%). Results from GEPIA database indicated that CHL1, MPP5, and SORT1 could be seen as promising target genes of the four-miRNA panel. Survival analysis of candidate miRNAs manifested that miR-155-5p was associated with the survival rate of RCC significantly. Conclusions: The four-miRNA panel in serum has a great potential to be non-invasive biomarkers for RCC sift to check.

MiR-23a-3p acts as an oncogene and potential prognostic biomarker by targeting PNRC2 in RCC.

BACKGROUND: Renal cell carcinoma (RCC) is a most common kidney malignancy, with atypical symptoms in the early stage and poor outcome in the late stage. Recently, emerging evidence revealed that some miRNAs play an essential role in the tumorigenesis and progression of RCC. Therefore, the aim of this study is that understand the detailed molecular mechanism of miR-23a-3p in RCC and identify its potential clinical value. METHODS: In this study, RT-qPCR, wound scratch assay, cell proliferation assay, transwell assay and flow cytometry assay were performed to detect miR-23a-3p expression and its proliferation, migration and apoptosis in RCC. The bioinformatics analysis, RT-qPCR, western blot and luciferase reporter assay were performed to discern and examine the relationship between miR-23a-3p and its potential targets. Moreover, we analyzed the relationship between miR-23a-3p expression and clinicopathological variables or overall survival (OS) from 118 formalin-fixed paraffin-embedded RCC samples. RESULTS: miR-23a-3p is significantly up-regulated in RCC tissue samples, RCC cell lines and the TCGA database. Upregulating miR-23a-3p enhances, while silencing miR-23a-3p suppresses cell viability, proliferation and mobility in ACHN and 786-O cell lines. Besides, overexpression of miR-23a-3p inhibits the cell apoptosis. Then our study further reveals that miR-23a-3p regulates tumorigenesis by targeting Proline-Rich Nuclear Receptor Coactivator 2 (PNRC2). Also, the cox proportional hazard regression analysis indicates that low expression of miR-23a-3p patients has a remarkable longer OS. CONCLUSIONS: Our results reveals that miR-23a-3p may not only serve as a new biomarker for prognosis but also serve as a new therapeutic strategy in the RCC treatment.

Oncogenic miR-425-5p is associated with cellular migration, proliferation and apoptosis in renal cell carcinoma.

An increasing number of studies have demonstrated the function of microRNAs (miRNAs) in the initiation and development of various types of cancer. Among them, miR-425-5p is proven to serve an important function in several types of cancer, including gastric, cervical cancer, and hepatocellular carcinoma. However, the function of miR-425-5p in renal cell carcinoma (RCC) remains unclear. In the present study, it was demonstrated that the expression level of miR-425-5p was upregulated in RCC tissues and cell lines compared with normal tissues and cell lines (P<0.05). Additionally, Cell Counting kit-8 and MTT assays were employed to assess cell viability and proliferation, whereas wound healing and Transwell assays were employed to examine migration and invasion. The results demonstrated that upregulation of miR-425-5p promoted cell viability and the invasion and migration of ACHN and 786O cells (P<0.05). Flow cytometric analysis confirmed that upregulation of miR-425-5p inhibited apoptosis of ACHN and 786O cells (P<0.05). Downregulation of miR-425-5p inhibited the viability and invasion and migration of ACHN and 786O cells (P<0.05). In the present study, upregulation of miR-425-5p inhibited apoptosis of ACHN and 786O cells whereas no differences in early apoptotic rate were observed between the inhibitor and inhibitor NC groups for 786O and ACHN cells. These results indicate that miR-425-5p may act as an oncogene in RCC.

Glomus tumor of the anterior urethra: A rare case report and review of the literature.

Glomus tumors are rare and benign neoplasms, which normally originate from peripheral soft tissue. To date, reported cases of glomus tumor occurring in genitourinary tract, particularly in the urethra, are exceedingly rare. The present study presented a rare case of glomus tumor of the anterior urethra in a 42 year-old male, his main complaints were a history of anterior urethra pain for 3 years, and a palpable and tender mass in the urethra for 2 weeks. Urethrocystoscopy examination and the resection of the urethral mass were performed. Pathological and immunohistochemical examination revealed that the mass was a benign glomus tumor. The patient remained in good condition by 6 month follow-up, and revealed no problems or recurrence following surgery. This is the first case, to the best of our knowledge, to present a glomus tumor occurring in a male's urethra and the present report provided a supplementary review for the previous cases and the literature.