Diagnostic Value of MicroRNAs for Urologic Cancers

MicroRNAs (miRNAs), particularly those extracted from the blood or tissues, have become the focus of urologic cancers research. However, the literature reviews on the accuracy of miRNA detection in urologic cancers have been inconsistent, leading us to perform this meta-analysis. Eligible studies were searched in PubMed and other databases. To calculate the pooled detection accuracy estimates, we used a bivariate random-effects meta-analysis model. According to the exclusion and inclusion criteria, 41 studies were included. Overall, the results showed sensitivity of 0.77 (95% CI: 0.74–0.80) and specificity of 0.76 (95% CI: 0.72–0.79), with an area under the SROC curve (AUC) of 0.83 (95% CI: 0.80–0.86). In addition, further subgroup analyses were also conducted. Firstly, the multiple miRNAs subgroup has significantly better diagnostic specificity than single miRNA subgroup among all these cancer types, while only bladder cancer (BC) and prostate cancer (PC) group with significantly greater diagnostic sensitivity with their multiple miRNA detection. Secondly, none of these cancer types showed significant differences on diagnostic sensitivity and specificity in their specimen and sample size subgroups. Thirdly, the diagnostic sensitivity between Asian (0.791, 95% CI: 0.748–0.827) and Caucasian (0.713, 95% CI: 0.666–0.756) in BC type was shown significant different with the P-value of 0.011. The results of our study suggested that miRNAs, particularly the multiple miRNAs, may play an important role in diagnosis and monitoring of the urologic cancers as superior biomarkers. (Medicine 94(37):e1272) Abbreviations: AUC = area under the SROC curve, BC = bladder cancer, DOR = diagnostic odds ratio, FN = false negatives, FP = false positives, NLR = negative likelihood ratio, PC = prostate cancer, PLR = positive likelihood ratios, RCC = renal cell i Zhang, MD, and Guanxin Shen, MD INTRODUCTION U rologic cancers are abnormal cell growth that occurs in the kidney, bladder, prostate, and testicles. Overall, about 1,607,602 new cases of urologic cancers were diagnosed worldwide in 2008, which ranked the second most common group of human malignancies. The main etiological factors of urologic cancers are considered to be occupational carcinogen exposure and smoking habit. Renal cell carcinoma (RCC), the most common neoplasm in kidney, accounts for nearly 3% of adult malignancies and its mortality rate is over 40%. RCC can be divided into several subtypes, such as clear cell (ccRCC), chromophobe (chRCC), and papillary (pRCC). The 5-year survival rate of RCC ranges from 15% to 50%, depending on tumor stage, treatment, and selection. For bladder cancer (BC), most of them are nonmuscle-invasive (NMIBC) lesions. Muscle-invasive (MIBC) lesions account for about 20% of the annual incidence of BC, amounting to approximately 15,000 deaths per year in the United States. The 5-year survival rate of BC ranges widely in different stages. The patients at early stage (I or II) are more likely to survive with a 5-year survival rate of 97%, while the patients at advanced stage (III or IV) have little chance to survive with only a 5-year survival rate of 6% since the tumor has already spread or invaded to other organs, which make it quite difficult to remove or kill cancer cells. Furthermore, prostate cancer (PC) is the second most common noncutaneous cancer in males. The potential environmental risk factors of PC were found in previous studies, such as diet. PC, due to its gradual progression and nonspecific symptoms, is usually diagnosed advanced stage. However, if PC patients could be diagnosed at its early stage, the treatment success rate would be greatly improved. Therefore, early detection of urologic cancers is both important and necessary for cancer patients to receive timely treatment. Currently, the conventional diagnostic methods of urologic cancers consist of urine-based test, cystoscopy, and upper-tract imaging. The urine cytology exhibits a high specificity (around 95%) but a low sensitivity (around 30%) for BC. The cystoscopy achieves the visualization of the internal urethra and bladder, which facilitates the fast and accurate diagnosis of urological diseases. But it may cause discomfort on patients during the process, and the invasiveness of cystoscopy may affect the life quality of patients. Moreover, the cystoscopy is a relatively expensive clinical examination. Early cancer detection could help patients manage their cancer in a better way, thus improve the survival rate of patients. The challenge for early cancer detection is that nonspecific symptoms could be observed easily at the early stage of cancer. Therefore, a novel noninvasive diagnostic biomarker with not only high sensitivity and specificity, but also friendly nature to patients, is urgently needed. NA) is an abundant class of small 20 to 25 nucleotides in length. MiRNA ved in the biological processes related to www.md-journal.com | 1 tumorigenesis, including cell proliferation, differentiation, and apoptosis. Since the first miRNA was discovered, miRNAs had been regarded as transcriptional byproducts for a long time. Not until miRNAs were found to be specifically deleted in leukemia did people realize the importance of them. Subsequent studies found that miRNAs are highly associated with various human cancers, including urologic cancers. For example, 4 miRNAs (miR-28, -185, -27, and 7f-2) were found significantly upregulated in RCC patients compared with healthy people. Overexpression of 10 miRNAs (miR-223, -26b, -221, -103-1, -185, -23b, -203, -17-5p, -23a, and -205) was observed as well in BC patients. Besides, miRNA-21 expression distinguished pRCC and ccRCC from chRCC with 83% sensitivity and 90% specificity. MiRNA375, -143, and -145 were also found with high level sensitivity and specificity in PC detection. Furthermore, it is found that miRNAs exist in blood, urine, and tissue with stable concentration. Therefore, compared with DNA or protein, miRNA might be a predominant biomarker from the biological standpoint. Subsequent studies have indicated that unique miRNA may lead to the urologic cancers. However, studies with inconsistent results have also been reported. In order to further explore the clinical applicability of miRNAs for urologic cancers, we conducted this systematic meta-analysis based on all relevant studies. MATERIALS AND METHODS