Prostate cancer (PCa) is the development of cancer in the prostate associated with a substantial morbidity and mortality [
]. It has reported that 233,000 new cases and 29,480 deaths occurred in the year 2014 [
]. Early diagnosis and treatment before tumor metastasizes is crucial for improving the patient survival [
]. The 5 year survival ratio for men diagnosed while the PCa is localized is nearly 100 %. And only 28 % of the men who diagnosed with metastatic PCa survive beyond 5 years [
]. There are still to be challenges for the early diagnosis of PCa due to its variable presentation [
Diagnostic testing for PCa has been widely studied and searches from biomarkers [
], such as the prostate-specific antigen (PSA) assay [
], to radiologic imaging, such as magnetic resonance imaging (MRI) [
], and Biopsy [
]. Although widely used as a diagnosis tool, serum PSA assays are sensitive but not specific enough to detecting PCa [
]. Novel biomarkers with enhanced detective accuracy would greatly assist the diagnosis of PCa [
Recently, microRNAs (miRNAs) have been found to play crucial roles in many cancer cellular processes, such as proliferation [
], differentiation [
] and apoptosis [
]. MiRNAs are small, endogenous, noncoding RNAs with single-stranded RNA that regulate gene expression by combine with messenger RNAs (mRNAs) and inhibiting the translation or promoting degradation of mRNA [
]. Our research found that miR-410-5p were secreted by prostate cancer cells and released into peripheral blood. We therefore sought to explore the plasma miR-410-5p as biomarkers for the diagnosis of PCa.
PCa has a nonspecific clinical biomarker presentation and is hard to diagnose [
]. Although great progress has been found in the detection and exclusion of PCa with the advent of PSA assay [
], radiologic imaging [
] and biopsy [
], there is still a superior need for specific and reliable biomarker for the detection early diagnostic testing of PCa. In our study, we confirmed serum miR-410-5p as a potential biomarker for PCa [
]. Ideally, a biomarker should be repeatable and have a high specificity and sensitivity for the diagnosis of a pathognomonic disease [
]. miRNAs are suitable potential biomarkers because of their fulfilling many of these criteria [
]. Furthermore, miRNAs are present in human peripheral blood in a greatly stable form that is protected from RNase activity and remain stable even in harsh conditions [
]. The stability, lower structure complexity, and lack of modifications make circulating miRNAs to be ideal diagnostic biomarker candidates [
]. The high specificity and sensitivity of miRNA detection using reverse transcription and qPCR may create accurate cut-off values for diagnosis. Until now, the function of serum miR-410-5p in PCa has not been reported. As confirmed by the miR-410-5p in this study, the application of miRNAs as minimally stable and sensitive biomarkers would result in great breakthroughs for the diagnosis of common disease [
PSA assay and biopsy test is widely used in the clinical PCa diagnosis. The sensitivity of PSA assay alone was 82.4 %, whereas the combination of PSA assay and biopsy test increased the sensitivity to 87.1 % [
]. However, the specificity of PSA assay is not enough to make a definite diagnosis on PCa, and biopsy is a traumatic test on prostate and cannot improve the quality-adjusted life-year (QALY) [
]. Plasma miR-410-5p might be an appropriate alternative. In addition, using plasma miR-410-5p was not a traumatic test and the co-diagnosis improves the specificity of PSA.
We have demonstrated that the plasma miR-410-5p level was not affected by non-cancer conditions. Plasma miR-410-5p could distinguish PCa cases from healthy controls or non-cancer cases with an AUC value of 0.8097 or 0.7652, which indicates that serum miR-410-5p could to be a potential biomarker to diagnose PCa. Furthermore, our recent research confirmed that the expression of miR-410-5p was 7.5-fold higher in the peripheral blood dendritic cells (DCs) of PCa patients compared to non-cancer controls. In this study, the serum miR-410-5p level in 26 patients with chronic prostatitis and 14 with an acute urinary tract infection was similar to the healthy controls. This result may suggest the function of miR-410-5p and give an explanation for the expression and secrete of miR-410-5p.
Our study was subject to several limitations. First, for clinical study, 327 patients (include 149 PCa patients) were relatively small in scale. And the results will require further replication in independent studies of PCa. Second, it would to be necessary to study the function of miR-410-5p in both PCa and other-disease patients. Third, it would be helpful to research whether combining the values of serum miR-410-5p content and PSA assay would greatly enhance the sensitivity and specificity for plasma miR-410-5p. Further studies are needed to resolve this tissue specificity. However, the PSA assay was a high-sensitivity and low-specific diagnostic method because it is also positive in the patients with prostatitis, benign prostatic hyperplasia, and other prostate diseases [
]. The specificity of miR-410-5p in diagnosing PCa was better than PSA assay in this study. Forth, further study is required to determine the additional benefit of miR-410-5p in staging and prognostic of prostate cancer. Fourth, the function of plasma miR-410-5p is still unclear. It is commonly speculated that circulating miRNAs play key role in maintaining the homeostatic state of the circulatory system [
]. But our research revealed that miR-410-5p assembling in DCs. Whether plasma miR-410-5p can trigger some pathogenic effects in dysfunction of DCs in PCa patients remains unclear. Finally, the pathogenic mechanism of miR-410-5p levels and the relationship with PCa is unclear. Our prior studies have confirmed that the release of miR-410-5p from prostate cancer cells may be cause of the immunologic escaping in PCa.
In conclusion, we confirmed that elevated serum miR-410-5p level is a potential biomarker for the diagnosis of PCa. Our results provide a basement for future efforts to develop serum miR-410-5p-based assays to diagnose PCa.
Jiaqi Wang and Dandan Zhang carried out the molecular biology studies, participated in the RNA extraction, miRNA reverse transcription and qPCR. Shanrong Liu, Jiaqi wang, Huamao Ye and Yijun Hu drafted the manuscript. Huamao Ye, Changjing Zuo and Yongwei Yu carried out the clinical assays. Long Wang and Guixia Xu participated in the samples’ collection and pre-processing. All authors read and approved the final manuscript.
This work was supported by National Natural Science Foundation (No: 81372763, 81272818), The China National Funds for Distinguished Young Scientists (No: 81425019), Specially-appointed Professor of Shanghai, National Natural Science Foundation (No: 81172448) and National Basic Research Program of China (2012CB518300). The “1255” Distinguished Young Scientists project of changhai hospital (No: CH125541300).
The authors declare that they have no competing interests.
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