Bladder cancer accounts for the most common type of urologic malignancy and presents high recurrence rate after surgical resection and adjuvant intravesical therapy. We aim to search for an early ...diagnostic biomarker in serum for bladder cancer in this study.
The expression profiles of miRNAs in serum samples of 112 bladder cancer patients and 112 healthy controls were detected with real-time polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curve and area under curve (AUC) analysis were performed to assess the diagnostic efficiency of miRNAs. Stepwise logic regression analysis was used to construct a diagnostic signature with highest sensitivity and specificity. Bioinformatics analysis was applied to explore the potential biological functions and mechanisms of candidate miRNAs.
Five miRNAs including miR-451a, miR-381-3p, miR-223-3p, miR-142-5p and miR-27b-3p were found differentially expressed in serum samples of bladder patients and healthy subjects. The diagnostic signature was constructed with miR-27b-3p, miR-381-3p and miR-451a. AUC of the three-miRNA signature was 0.894 (0.837-0.936, p < 0.001). The sensitivity and specificity of this signature were 86.90% and 77.38%, respectively, indicating that this signature has a good ability to diagnose bladder cancer.
The three-miRNA signature we constructed has favorable diagnostic capacity and may be a promising non-invasive biomarker in the early diagnosis of bladder cancer.
KEY MESSAGES
There is still no clinical utilization of serum miRNAs in the early detection of bladder cancer.
We screened and constructed a three-miRNA signature with the sensitivity of 86.90% and specificity of 77.38% which may be a promising non-invasive biomarker in the early diagnosis of bladder cancer.
Serum microRNAs (miRNAs), with their noticeable stability and unique expression pattern in patients with various diseases, are robust novel non-invasive biomarkers for cancer detection. The objective ...of this study was to identify specific serum miRNAs as potential biomarkers for screening lung adenocarcinoma. The study was divided into a screening phase, training phase, and validation phase. The expression of 46 serum miRNAs from lung adenocarcinoma (LUAD) patients and healthy controls (HCs) were examined in the screening phase. The expression of the most dysregulated miRNAs was further verified in training (30 LUAD vs. 30 HCs) and validation (82 LUAD vs. 90 HCs) phases. Seven serum miRNAs (miR-142-5p, miR-203a-5p, miR-409-3p, miR-223-3p, miR-150-5p, miR-486-5p and miR-146a-5p) in LUAD patients were significantly dysregulated compared to those in HCs. Their ability to diagnose lung cancer was also significant, with miR-142-5p (AUC = 0.743), miR-409-3p (AUC = 0.755), miR-223-3p (AUC = 0.828) and miR-146a-5p (AUC = 0.745) being more prominent. The combined use of these four could enhance diagnostic value (AUC = 0.933). Our findings define a distinct miRNA expression profile in the serum of LUAD patients. The four-miRNA panel (miR-142-5p, miR-409-3p, miR-223-3p and 146a-5p) may be considered as a novel, non-invasive biomarker for LUAD early detection.
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.
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.
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.
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.
Background:
Circulating miRNAs have been proved to be promising biomarkers for disease detection in recent years. The present study aimed at exploring available serum miRNA biomarkers for the ...detection of colorectal cancer.
Methods:
A three-phase study was performed to select and validate candidate miRNAs with significant dysregulation in colorectal cancer using quantitative reverse transcription-polymerase chain reaction. This study recruited 137 colorectal cancer patients and 145 healthy controls. The diagnostic values of miRNAs were evaluated by receiver operating characteristic analysis. Bioinformatics analyses were utilized to predict target genes of miRNAs, and to conduct functional annotation and enrichment.
Results:
miR-30e-3p, miR-31-5p, miR-34b-3p and miR-146a-5p, miR-148a-3p and miR-192-5p were significantly dysregulated in colorectal cancer serum when compared with healthy controls. The panel composed of miR-30e-3p, miR-146a-5p, and miR-148a-3p exhibited strong diagnostic ability. The area under the receiver operating characteristic curve of the three-miRNA panel was 0.883, with a sensitivity of 0.800 and specificity of 0.787.
Conclusion:
The present study identified a three-miRNA panel in serum with a strong diagnostic ability of colorectal cancer, which may be able to serve as a novel noninvasive biomarker for colorectal cancer detection.
Renal cell carcinoma (RCC) stands as the most prevalent form of urogenital cancer. However, there is currently no universally accepted method for predicting the prognosis of RCC. MiRNA holds great ...potential as a prognostic biomarker for RCC.
A total of 100 cases with complete paraffin specimens and over 5-year follow-up data meeting the requirements were collected. Utilizing the clinical information and follow-up data of the specimens, an information model was developed. The expression levels of eight microRNAs were identified using RT-qPCR. Finally, determine and analyze the clinical application value of these microRNAs as prognostic markers for RCC.
Significant differences were observed in the expression of two types of miRNAs (miR-378a-5p, miR-23a-5p) in RCC tissue, and three types of miRNAs (miR-378a-5p, miR-642a-5p, miR-23a-5p) were found to be linked to the prognosis of RCC. Establish biomarker combinations of miR-378a-5p, miR-642a-5p, and miR-23a-5p to evaluate RCC prognosis.
The combination of three microRNA groups (miR-378a-5p, miR-642a-5p, and miR-23a-5p) identified in paraffin section specimens of RCC in this study holds significant potential as biomarkers for assessing RCC prognosis.
Scouring of soil around large-diameter monopile will alter the stress history, and therefore the stiffness and strength of the soil at shallow depth, with important consequence to the lateral ...behavior of piles. The existing study is mainly focused on small-diameter piles under scouring, where the soil around a pile is analyzed with two simplified approaches: (I) simply removing the scour layers without changing the strength and stiffness of the remaining soils, or (II) solely considering the effects of stress history on the soil strength. This study aims to investigate and quantify the scour effect on the lateral behavior of monopile, based on an advanced hypoplastic model considering the influence of stress history on both soil stiffness and strength. It is revealed that ignorance about the stress history effect (due to scouring) underestimates the extent of the soil failure wedge around the monopile, while overestimates soil stiffness and strength. As a result, a large-diameter pile (diameter D = 5 m) in soft clay subjected to a souring depth of 0.5 D has experienced reductions in ultimate soil resistance and initial stiffness of the p-y curves by 40% and 26%, and thus an increase of pile head deflection by 49%. Due to the inadequacy to consider the stress history effects revealed above, the existing approach (I) has led to non-conservative estimation, while the approach (II) has resulted in an over-conservative prediction.
Although pile foundations are usually subjected to both lateral and vertical loads, there have been few studies on the pile response under the combined loadings. Moreover, those few studies led to ...inconsistent conclusions concerning the influence of vertical load on the lateral pile response. This study aims to investigate the effect of vertical load on the monotonic and cyclic lateral response of piles in normally consolidated (NC) and over-consolidated (OC) clay through a series of centrifuge tests. Three-dimensional finite element analyses using an advanced hypoplastic clay model were also performed to gain deep insight into the mechanism. It is revealed that after applying the vertical load and allowing the dissipation of the induced excess pore pressure, the lateral initial stiffness and ultimate capacity of the pile in the NC clay increased by 10.0 and 49.4%, respectively. However, in the OC clay, the application of the vertical load resulted in a 12.6 and 32.4% reduction in the lateral pile initial stiffness and ultimate capacity, respectively, showing a distinct response from that in the NC clay. The above-mentioned distinct influence of vertical load for piles can be attributed to the different evolutions of stress ratio (
q/p
’) of the soil around the pile in the NC and OC clay, which determines the soil mobilisable shear strength and consequently the lateral pile responses.
Purpose
Renal cell carcinoma (RCC) accounts for about 120,000 death each year. Although surgery is a routine treatment, RCC could be fatal if not diagnosed at an early stage. This study aims to ...search for suitable serum biomarkers and construct a miRNA panel with high diagnostic sensitivity or specificity.
Methods
Totally 146 RCC patients and 150 normal control were involved in this three-stage study. Serum expression levels of 30 miRNAs selected from literature were tested by reverse transcription quantitative PCR (RT-qPCR) in the screening stage, the testing stage, and the validation stage. The diagnostic efficiency of miRNAs was evaluated by receiver operating characteristic (ROC) curve and area under curve (AUC) analysis. A panel with the highest diagnostic efficiency was constructed by backward stepwise logistic regression analysis. Additionally, bioinformatics analysis was used to investigate potential biological functions and mechanisms of candidate miRNAs.
Results
MiR-224-5p, miR-34b-3p, miR-129-2-3p and miR-182-5p with low to moderate diagnostic ability (AUC = 0.692, 0.778, 0.687 and 0.745, respectively) were selected as candidate miRNAs after the three-stage study. The final diagnostic panel was consisted by miR-224-5p, miR-34b-3p and miR-182-5p with AUC = 0.855. No significance has been found between these four miRNAs and tumor location, Fuhrman Grade and AJCC clinical stages of RCC. Bioinformatic analysis suggested that the three-miRNAs panel may participate in tumorigenesis of RCC by targeting CORO1C.
Conclusions
The three-miRNA panel in serum could serve as a non-invasive diagnostic biomarker of RCC.
Prostate cancer (PCa) is one of the most prevalent malignancies affecting the male life cycle. The incidence and mortality of prostate cancer are also increasing every year. Detection of MicroRNA ...expression in serum to diagnose prostate cancer and determine prognosis is a very promising non-invasive modality.
A total of 224 study participants were included in our study, including 112 prostate cancer patients and 112 healthy adults. The experiment consisted of three main phases, namely, the screening phase, the testing phase, and the validation phase. The expression levels of serum miRNAs in patients and healthy adults were detected using quantitative reverse transcription-polymerase chain reaction. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate the diagnostic ability, specificity, and sensitivity of the candidate miRNAs.
Eventually, three miRNAs most relevant to prostate cancer diagnosis were selected, namely, miR-106b-5p, miR-129-1-3p and miR-381-3p. We used these three miRNAs to construct a diagnostic panel with very high diagnostic potential for prostate cancer, which had an AUC of 0.912 95% confidence interval (CI): 0.858 to 0.950;
< 0.001; sensitivity = 91.67%; specificity = 79.76%. In addition, the three target genes (DTNA, GJB1, and TRPC4) we searched for are also expected to be used for prostate cancer diagnosis and treatment in the future.
PDF
