microRNAs In Renal Cell Carcinoma Research Articles

Meta-analysis of the diagnostic value of exosomal microRNAs in renal cell carcinoma

AimThis meta-analysis aims to evaluate the potential of exosomal microRNAs(Exo-miRs) as diagnostic biomarkers for renal cell carcinoma(RCC).MethodsClinical studies reporting the use of Exo-miRs in the diagnosis of RCC were retrieved from PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, and Chinese Biomedical Literature Database (SinoMed). After relevant data were screened and extracted, the quality of the included studies was assessed using the QUADAS-2 tool. The Meta-disc (version 1.4) software was used to analyze the heterogeneity of threshold/non-threshold effects in the included studies. The Stata MP (version 16.0) software was used to calculate sensitivity(Sen), specificity(Spe), positive likelihood ratio(+LR), negative likelihood ratio(-LR), area under the curve(AUC), diagnostic odds ratio(DOR), and publication bias.ResultsA total of 11 studies were included in this meta-analysis. Spearman correlation coefficient was 0.319 (P = 0.075; >0.05), indicating no threshold effects. The pooled Sen, Spe, +LR, -LR, DOR, and AUC were 0.73 (95% CI, 0.68–0.78), 0.81 (95% CI, 0.76–0.85), 3.80 (95% CI, 3.02–4.77), 0.33 (95% CI, 0.28–0.40), 11.48 (95% CI, 8.27–15.95), and 0.84 (95% CI, 0.80–0.87), respectively. No publication bias was detected among the included studies.ConclusionThe expression of Exo-miRs plays an important role in the diagnosis of RCC. However, owing to the limited number of included studies and heterogeneity among them, further clinical research is necessary to verify the findings of this meta-analysis.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023445956.

Three LHPP gene-targeting co-expressed microRNAs (microRNA-765, microRNA-21, and microRNA-144) promote proliferation, epithelial-mesenchymal transition, invasion, and are independent prognostic biomarkers in renal cell carcinomas patients.

BackgroundRenal cell carcinoma (RCC) is one of the highly malignant tumors in the world. Global Cancer Statistics 2020 estimated that there were 179,368 deaths from kidney tumors. Therefore, exploring the prognostic biomarkers of RCC is of great significance for RCC patients. This study aims to explore the potential mechanism and prognostic value of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) gene‐targeting co‐expression microRNAs in RCC patients.MethodsA total of 60 RCC patients were included. Quantitative real‐time PCR (qRT‐PCR), western blotting, and immunohistochemistry were used for LHPP, microRNA‐765, microRNA‐21, and microRNA‐144 levels evaluation. Cell Counting Kit‐8 assay, dual‐luciferase reporter gene assay, invasion assay, and RNA fluorescence in situ hybridization were used for functional analyses.ResultsCompared with adjacent tissues, LHPP levels in cancer tissues were significantly increased (p < .001). Herein, we confirmed that microRNA‐765, microRNA‐21, and microRNA‐144 were direct biological targets of LHPP. MicroRNA‐765 (r = −0.570, p < 0.001), microRNA‐21 (r = −0.495, p < .001), and microRNA‐144 (r = −0.463, p < .001) expression levels were negatively correlated with LHPP expression levels. The high expression levels of microRNA‐765, microRNA‐21, and microRNA‐144 in RCC tissues were associated with poor differentiation, recurrence, and poor prognosis (p < .05). In vitro, microRNA‐765, microRNA‐21, and microRNA‐144 act as oncogenes to promote proliferation, invasion, and epithelial‐mesenchymal transition (EMT) through targeting LHPP.ConclusionsMicroRNA‐765, microRNA‐21, and microRNA‐144 are independent risk biomarkers for RCC patients. Inhibiting the expression levels of microRNA‐765, microRNA‐21, and microRNA‐144 can reduce the proliferation, EMT, and invasion of RCC cells. Therefore, the above three microRNAs are expected to become molecular biomarkers for RCC therapy.

Unveiling the World of Circulating and Exosomal microRNAs in Renal Cell Carcinoma.

Simple SummaryLiquid biopsies have emerged as a new tool for early diagnosis. In renal cell carcinoma, this need is also evident and may represent an improvement in disease management. Hence, in this review we discuss the most updated advances in the assessment of miRNAs in liquid biopsies. Moreover, we explore the potential of circulating or exosome miRNAs in renal cell carcinoma to overcome the tissue biopsies limitations.Renal cell carcinoma is the third most common urological cancer. Despite recent advances, late diagnosis and poor prognosis of advanced-stage disease remain a major problem, entailing the need for novel early diagnosis tools. Liquid biopsies represent a promising minimally invasive clinical tool, providing real-time feedback of tumor behavior and biological potential, addressing its clonal evolution and representing its heterogeneity. In particular, the study of circulating microRNAs and exosomal microRNAs in liquid biopsies experienced an exponential increase in recent years, considering the potential clinical utility and available technology that facilitates implementation. Herein, we provide a systematic review on the applicability of these biomarkers in the context of renal cell carcinoma. Issues such as additional benefit from extracting microRNAs transported in extracellular vesicles, use for subtyping and representation of different histological types, correlation with tumor burden, and prediction of patient outcome are also addressed. Despite the need for more conclusive research, available data indicate that exosomal microRNAs represent a robust minimally invasive biomarker for renal cell carcinoma. Thus, innovative research on microRNAs and novel detection techniques are likely to provide clinically relevant biomarkers, overcome current clinical challenges, and improve patient management.

MicroRNAs in Renal Cell Carcinoma.

New therapies based on the targeting of signal pathways (such as VHL/HIF-1) common to most renal cell carcinomas (RCC), have greatly improved the outlook for sufferers of this disease. Given the growing reputation of many microRNAs (miRNAs) as both tumor suppressors and oncogenes, the measurement and manipulation of these small nucleotides in RCC patients may provide yet another valuable advance in renal cancer diagnosis and treatment. The present review summarizes the current literature on the role of microRNAs in RCC development and progression emphasizing the interaction of specific miRNAs with both oncogenic and tumor suppressor pathways of particular importance in renal cancer.

MicroRNAs in renal cell carcinoma: a systematic review of clinical implications (Review).

Despite recent advances in the understanding of the biology of renal cell carcinoma (RCC), successful surgical treatment and implementation of novel-targeted therapies, the prognosis for RCC patients remains poor. Late presentation, tumor heterogeneity and in particular the lack of molecular biomarkers for early detection, classification and the surveillance of RCC treatments are major obstacles. The increasing knowledge regarding the functional role of microRNAs (miRNAs) in pathophysiological processes may provide an important link to the identification of suitable therapeutic targets and diagnostic/prognostic biomarkers for RCC. The aim of this review was to provide new insight into the function of miRNAs in the pathogenesis of RCC and to emphasize their potential as diagnostic and prognostic markers, as well as therapeutic targets.

MicroRNAs in Renal Cell Carcinoma: Diagnostic Implications of Serum miR-1233 Levels

BackgroundMicroRNA expression is altered in cancer cells, and microRNAs could serve as diagnostic/prognostic biomarker for cancer patients. Our study was designed to analyze circulating serum microRNAs in patients with renal cell carcinoma (RCC).Methodology/Principal FindingsWe first explored microRNA expression profiles in tissue and serum using TaqMan Low Density Arrays in each six malignant and benign samples: Although 109 microRNAs were circulating at higher levels in cancer patients' serum, we identified only 36 microRNAs with up-regulation in RCC tissue and serum of RCC patients. Seven candidate microRNAs were selected for verification based on the finding of up-regulation in serum and tissue of RCC patients: miR-7-1*, miR-93, miR-106b*, miR-210, miR-320b, miR-1233 and miR-1290 levels in serum of healthy controls (n = 30) and RCC (n = 33) patients were determined using quantitative real-time PCR (TaqMan MicroRNA Assays). miR-1233 was increased in RCC patients, and thus validated in a multicentre cohort of 84 RCC patients and 93 healthy controls using quantitative real-time PCR (sensitivity 77.4%, specificity 37.6%, AUC 0.588). We also studied 13 samples of patients with angiomyolipoma or oncocytoma, whose serum miR-1233 levels were similar to RCC patients. Circulating microRNAs were not correlated with clinical-pathological parameters.Conclusions/SignificanceMicroRNA levels are distinctly increased in cancer patients, although only a small subset of circulating microRNAs has a tumor-specific origin. We identify circulating miR-1233 as a potential biomarker for RCC patients. Larger-scaled studies are warranted to fully explore the role of circulating microRNAs in RCC.

Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy

BackgroundMicroRNAs are endogenously expressed regulatory noncoding RNAs. Previous studies have shown altered expression levels of several microRNAs in renal cell carcinoma.MethodsWe examined the expression levels of selected microRNAs in 38 samples of conventional renal cell carcinoma (RCC) and 10 samples of non-tumoral renal parenchyma using TaqMan real-time PCR method.ResultsThe expression levels of miRNA-155 (p < 0.0001), miRNA-210 (p < 0.0001), miRNA-106a (p < 0.0001) and miRNA-106b (p < 0.0001) were significantly over-expressed in tumor tissue, whereas the expression of miRNA-141 (p < 0.0001) and miRNA-200c (p < 0.0001) were significantly decreased in RCC samples. There were no significant differences between expression levels of miRNA-182 and miRNA-200b in tumor samples and renal parenchyma. Our data suggest that expression levels of miRNA-106b are significantly lower in tumors of patients who developed metastasis (p = 0.030) and miR-106b is a potential predictive marker of early metastasis after nephrectomy in RCC patients (long-rank p = 0.032).ConclusionsWe have confirmed previous observations obtained by miRNA microarray analysis using standardized real-time PCR method. For the first time, we have identified a prognostic significance of miRNA-106b, which, after validation on a larger group of patients, maybe useful as a promising biomarker in patients with RCC.