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Bladder cancer (BC) is the tenth most common cancer in the world. Serum microRNA (miRNA) profiles previously have been reported as non-invasive biomarkers in cancer screening. The non-invasive and reliable diagnostic biomarkers are urgently needed for detecting BC, while cystoscopy is invasive. Our study aimed to identify candidate miRNAs in serum as potential diagnostic biomarkers for BC detection.This study was including the screening stage, training stage, and validation stage with 137 BC patients and 127 healthy controls (HCs). We identified the expression of 28 serum miRNAs from 5 BC pools and 3 HC pools in the initial screening stage. The other 112 BC patients and 112 HCs were randomly divided into training stage with 30 BC patients and 30 HCs and validation stages with 82 BC patients and 82 HCs. These HCs matched BC patients based on age and gender with P value0.05. Identified dysregulated miRNAs were further confirmed in the training stage, and validation stages by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The diagnostic value of miRNAs was assessed by receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC). Target genes of 3 candidate miRNAs were predicted by bioinformatic analysis.Five miRNAs (miR-106a-5p, miR-145-5p, miR-132-3p, miR-7-5p and miR-148b-3p) in serum were obviously dysregulated in BC patients compared to HCs. The ability to diagnose BC of 3 candidate miRNAs was estimated by AUC, with miR-132-3p (AUC =0.781; sensitivity =68.29%, specificity =81.71%), miR-7-5p (AUC =0.778; sensitivity =59.76%, specificity =84.15%) and miR-148b-3p (AUC =0.837; sensitivity =81.71%, specificity =71.95%). Combined application of these candidate miRNAs with parallel test could improve the diagnostic value (AUC =0.922; sensitivity =90.24%, specificity =81.71%).A three-miRNA panel in serum was identified for BC diagnosis in our study, which HCs were used for differential diagnosis. The three-miRNA panel (miR-132-3p, miR-7-5p, and miR-148b-3p) might be performed as a non-invasive and convenient diagnostic tool for BC screening and diagnosis.

The relationship between environmental regulation and firm productivity has been widely debated but inconsistencies in findings across different studies. Using detailed firm-level micro-data from 2000 to 2007, this paper employs difference-in-difference combined with matching based on entropy balancing method to explore the effect of environmental regulation on firm total factor productivity (TFP) in pulp and paper industry in China. Our main findings are as following: Firstly, stricter environmental regulation, as represented by the Wastewater Discharge Standards for Pulp and Paper Industry in Shandong province, increases firm TFP significantly. Moreover, the coefficients of interest are robust to multiple robustness checks. Secondly, dynamic effects estimates reveal that when faced with this phase-in environmental regulation, firms take the foreseeably increasing strictness into account from the very beginning and prefer to take one-step adjustment to reach full compliance. Thirdly, potential mechanism analysis finds that the positive effect mainly comes from the improvement of resource allocation efficiency within firms. Fourthly, the heterogeneity test indicates that the effect of environmental regulation on firm TFP is heterogeneous across firms with different sizes, ages, ownerships, capital intensity, and export status. Finally, this paper provides convincing and insightful evidence that environmental regulation has the potential to achieve the dual goals of environmental sustainability and economic growth and is thus of broader significance for understanding the enforcement of environmental regulation in developing countries.

Aim: Breast cancer, especially invasive ductal carcinoma (IDC), is the cause of a great clinical burden. miRNA could be considered as a noninvasive biomarkers for IDC diagnosis. Materials & methods: Two hundred and sixty participants (135 IDC patients and 125 healthy controls) were enrolled in a three-cohort study. The expression of 28 miRNAs in serum were detected with quantitative reverse transcription-PCR. Bioinformatic analysis was used for predicting the target genes of three selected miRNAs. Results: The expression level of seven miRNAs (miR-9-5p, miR-34b-3p, miR-1-3p, miR-146a-5p, miR-20a-5p, miR-34a-5p, miR-125b-5p) was discrepant at the validation cohort. Through statistical test, a three-miRNA panel (miR-9-5p, miR-34b-3p, miR-146a-5p) was significant for IDC diagnosis (AUC = 0.880, sensitivity = 86.25%, specificity = 81.25%). Conclusion: The three-miRNA panel in serum could be used as a noninvasive biomarker in the diagnosis of IDC.

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.

Background. MicroRNAs (miRNAs) have been applied to cancer diagnosis taking into account their role in tumorigenesis. The main purpose of our study was to confirm the possibility of using miRNAs as noninvasive biomarkers for stomach adenocarcinoma (STAD) diagnosis. Methods. A total of 246 participants (130 STAD patients and 116 healthy controls (HCs)) were enrolled in this 3-phase study. Five STAD pools and 3 HC pools (with 4 participants in each pool) were used for the screening of the 28 miRNAs using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The training phase (30 STAD patients vs. 24 HCs) and validation phase (80 STAD patients vs. 80 HCs) were used to further verify the identity of these miRNAs. Kaplan–Meier survival analysis and bioinformatics analysis were also used. Results. The expression levels of miR-125b-5p and miR-196a-5p were upregulated in STAD serum, compared with the HCs, while miR-1-3p and miR-149-5p showed the opposite result. A four-serum miRNA panel was constructed, and the area under the receiver operating characteristic curve (AUC) was found to be 0.892 (95% CI: 0.834 to 0.936, sensitivity = 86.25 % , specificity = 78.75 % ). Only miR-125b-5p expression showed a significant difference between STAD patients and NCs in the survival analysis. The neurotrophin signaling pathway was associated with 4 miRNAs identified in STAD patients. Conclusion. The four-serum miRNA panel has great potential to be used as a noninvasive biomarker for STAD diagnosis.

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) 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. 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. 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. The three-miRNA panel in serum could serve as a non-invasive diagnostic biomarker of RCC.

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.

Nasopharyngeal carcinoma is cancer with unique epidemiological characteristics, showing obvious ethnicity, gender, and geographical prevalence. More and more evidence shows that microRNAs are stable in serum and are specific to different tumor types. Therefore, miRNA is a new non-invasive biomarker for cancer detection.The experiment is divided into three stages, namely, the screening stage, the training stage, and the verification stage. We took 54 patients with nasopharyngeal carcinoma and 108 healthy controls as the research objects. We use the receiver-operating characteristic (ROC) curve and area under the ROC curve (AUC) to evaluate the diagnostic value of miRNA. Finally, a three-miRNA panel with high diagnostic efficiency was constructed. In addition, we conducted biological information analysis of these miRNAs to explore their functions.In NPC patients, the expression of five serum miRNAs (miR-29c-3p, miR-143-5p, miR-150-5p, miR-145-3p, and miR-205-5p) is significantly dysregulated. Among them, the diagnostic value of these three miRNAs (miR-29c-3p, AUC = 0.702; miR-143-5p, AUC = 0.733; and miR-205-5p, AUC = 787) is more prominent. The diagnostic panel constructed by them has a higher diagnostic value (AUC = 0.902). Through the analysis of the TCGA data set, the target gene of the three-miRNA panel may be KLF7, NRG1, SH3BGRL2, and SYNPO2.The three-miRNA panel (miR-29c-3p, miR-143-5p, and miR-205-5p) may become a novel non-invasive biological marker for nasopharyngeal cancer screening.

Background: miR-142-3p has proved to be involved in tumorigenesis and the development of renal cell carcinoma. The present study aimed to explore the prognostic value of miR-142-3p. Methods: Total RNA was extracted from renal cell carcinoma specimens and the expression level of miR-142-3p was measured. Pearson Chi-square test, Kaplan–Meier analysis, as well as univariate and multivariate regression analysis were performed to determine the correlation between miR-142-3p and the prognosis of renal cell carcinoma patients. Receiver operating characteristic curves were constructed to evaluate the predictive efficiency of miR-142-3p for the prognosis of renal cell carcinoma patients. Data from The Cancer Genome Atlas (TCGA) were utilized to validate our findings. Results: Our results demonstrated that upregulation of miR-142-3p was correlated with shorter overall survival (P=0.002) and was, in the meantime, an independent prognostic factor for renal cell carcinoma patients (P=0.002). The receiver operating characteristic curve combining miR-142-3p expression with tumor stage showed an area under the curve of 0.633 (95% confidence interval 0.563, 0.702). The result of TCGA data was consistent with our findings. Conclusions: Our results suggest miR-142-3p expression is correlated with poor prognosis of renal cell carcinoma patients and may serve as a prognostic biomarker in the future.

The diagnosis of renal cell carcinoma (RCC) is often made late since there is no early symptom, which thus results in dismal patient prognosis. As a result, new biomarkers are urgently needed and efforts should be made to identify their functions in predicting RCC prognosis. microRNAs (miRNAs) are a class of small noncoding RNAs that are about 20‐22 nucleotides in length, and they have been demonstrated to function as prognostic markers in numerous tumors. This study aimed to assess the role of miR‐30b‐5p in predicting the prognosis of RCC postoperatively. In this study, RNA was extracted from 284 formalin‐fixed and paraffin‐embedded kidney cancer tissue samples. After cDNA synthesis, real‐time quantitative PCR (RT‐qPCR) was adopted for detecting the relative miR‐30b‐5p level. Then, the Kaplan‐Meier method, Cox regression analysis, and the receiver operating characteristic curve analysis were applied in analyzing the miR‐30b‐5p effect on the prognosis for patients. Our findings indicated that, following adjustment for age, gender, tumor stage, and tumor size, patients with low miR‐30b‐5p expression had remarkably longer overall survival. Thus, the miR‐30b‐5p level might be related to RCC prognosis., As observed from the survival curves tested by Kaplan‐Meier method, high miR‐30b‐5p expression was correlated with dismal survival of RCC patients (P = .005), which was similar with the data obtained from TGGA (P = .0388).

Background: Bladder cancer (BC) is a common tumor in the urinary system with a high recurrence rate. The individualized treatment and follow-up after surgery is the key to a successful outcome. Currently, the surveillance strategies are mainly depending on tumor stage and grade. Previous evidence has proved that tumor grade was a significant and independent risk factor of BC recurrence. Exploring the grade-related genes may provide us a new approach to predict prognosis and guide the post-operative treatment in BC patients. Methods: In this study, the weighted gene co-expression network analysis was applied to identify the hub gene module correlated with BC grade using GSE71576. After constructing a protein–protein interaction (PPI) network with the hub genes inside the hub gene module, we identified some potential core genes. TCGA and another independent dataset were used for further validation. Results: The results revealed that the expression of AURKA, CCNA2, CCNB1, KIF11, TTK, BUB1B, BUB1, and CDK1 were significantly higher in high-grade BC, showing a strong ability to distinguish BC grade. The expression levels of the 8 genes in normal, paracancerous, tumorous, and recurrent bladder tissues were progressively increased. By conducting survival analysis, we proved their prognostic value in predicting the recurrence of BC. Eventually, we constructed a prognostic nomogram by combining the 8-core-gene panel with clinicopathologic features, which had shown great performance in predicting the recurrence of BC. Conclusion: We identified 8 core genes that revealed a significant correlation with the tumor grade as well as the recurrence of BC. Finally, we proved the value of a novel prognostic nomogram for predicting the relapse-free survival of BC patients after surgery, which could guide their treatment and follow-up.

Objective Previous research has shown that the miR‐130 family is closely related to the occurrence and development of bladder cancer. We hope to use the miR‐130 family members as new, non‐invasive, and easily detectable biomarkers for bladder cancer. Methods We analyzed 428 cases in The Cancer Genome Atlas‐Bladder Urothelial Carcinoma database and verified that the miR‐130 family members were significantly overexpressed in bladder cancer. A total of 74 bladder cancer patients and 90 controls were enrolled. The relative expression of the miR‐130 family in serum was detected using quantitative reverse transcription‐polymerase chain reaction. The diagnostic efficacy of the miR‐130 family members was determined using the receiver operating characteristic method (ROC), and a diagnostic panel was built using logistic regression. The results of the study were further confirmed in an external validation set of 492 samples from the Gene Expression Omnibus database. Results The expression of the miR‐130 family members (except for miR‐301b‐3p) in the serum of bladder cancer patients was higher than that in the controls. The diagnostic capabilities for bladder cancer were 0.847 (miR‐130a‐3p), 0.762 (miR‐130b‐3p), and 0.892 (miR‐301a‐3p). We established a three‐miRNA panel with an area under the ROC curve as high as 0.961, indicating that it is a promising clinical diagnostic biomarker of bladder cancer with high sensitivity and specificity. Conclusion The expression levels of miR‐130 family members in serum can effectively distinguish the bladder cancer patients from healthy controls. This finding will facilitate the clinical diagnosis of bladder cancer., The miR‐130 family members are highly expressed in the serum of bladder cancer patients. Their expression levels can effectively distinguish bladder cancer patients from healthy controls.

Background The aim of the study was to identify serum microRNAs (miRNAs) as potential biomarkers for screening renal cell carcinoma. Methods The study was divided into three stages, including screening stage, training stage, and validation stage. In the screening stage, we examined the expression of 30 serum miRNAs from healthy controls (HCs) and renal cell carcinoma (RCC) patients. We further studied the dysregulated miRNAs in training (30 RCC and 26 HCs) and validation (73 RCC and 80 HCs) stages. We estimated the diagnostic value of miRNAs by receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC). Finally, bioinformatics analysis were performed towards target genes of differentially expressed miRNAs. Results Six serum miRNAs (miR-17-5p, miR-20a-5p, miR-21-5p, miR-150-5p, miR-145-5p and miR-146a-5p) in RCC patients were obviously differentially expressed compared to those in HCs in training stage and validation stage. To increase diagnostic value, we combined these six serum miRNAs and made a four-microRNA (miR-21-5p, miR-150-5p, miR-145-5p and miR-146a-5p) panel, and AUC of the panel was 0.938 (95% CI: 0.889-0.971; sensitivity=90.79%, specificity=93.75%). The genes targeted by these miRNAs were suggested that they may be involved in the process of cancers by the bioinformatics analysis. Conclusions Our study was performing a four-microRNA panel in serum for screening enal cell carcinoma. The four-miRNA panel (miR-21-5p, miR-150-5p, miR-145-5p and miR-146a-5p) may be perform as a biomarker without invasiveness for RCC screening.

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.

Clear cell renal cell carcinoma (ccRCC) is a common malignancy, yet, the mechanisms underlying tumorigenesis remain unclear. Several miRNAs have been implicated in the development of RCC previously via regulation of target gene expression. As miR-625-3p has recently been identified to play a role in development of other malignancies and is reportedly upregulated in ccRCC, we sought to investigate the role of this miRNA in the progression of ccRCC. Analysis of 30 paired fresh ccRCC tissues and adjacent normal renal tissues revealed that the expression of miR-625-3p was increased in ccRCC tissues compared to normal tissues. Subsequently, in 136 formalin-fixed paraffin-embedded ccRCC tissues, the increased miR-625-3p expression was correlated with poor prognosis for ccRCC patients. The diagnostic value of miR-625-3p was identified in 50 ccRCC patients and 74 healthy controls by ROC curve. miR-625-3p was decreased in serum of ccRCC patients compared to healthy individuals. miR-625-3p could serve as a promising serum biomarker for yielding an area under the receiver operating characteristic curve of 0.792 with 70.3% sensitivity and 80.0% specificity in discriminating ccRCC from healthy individuals. Using in vitro functional assays, we found that overexpression of miR-625-3p promoted migration and invasion of ccRCC cells but reduced ccRCC cell apoptosis. Inhibition of miR-625-3p, on the other hand, exerted the opposite effects. Bioinformatic analyses indicated that predicted gene targets of miR-625-3p are correlated with lower overall survival of ccRCC patients. Together, these findings demonstrate that miR-625-3p promotes ccRCC migration and invasion and reduces apoptosis, providing a prognostic marker for survival and a potential diagnostic and therapeutic target against ccRCC.

Objective The present study aims to determine the association of microRNA-106b-5p (miR-106b-5p) expression with the clinicopathological features and prognosis of renal cell carcinoma (RCC). Patents and methods The formalin-fixed paraffin-embedded(FFPE) Tumor tissues were collected from 284 RCC patients. The expression of miR-106b-5p was examined by Reverse Transcription Real-time Quantitative Polymerase Chain Reaction (RT-qPCR), followed by correlation analysis with clinicopathological features and prognosis. Patient survival analysis was determined by the Kaplan-Meier method using the log-rank test was used for patient survival analysis, and the univariate and multivariate analysis was determined by a Cox’s regression model. Results Kaplan-Meier analysis indicated that patients with high miR-106b-5p expression showed a significantly shorter overall survival, compared with patients with low miR-106b-5p expression (p = 0.001). Univariate and multivariate analysis considered miR-106b-5p expression as an independent risk factor for predicting the prognosis of RCC patients. No significant evident showed that the expression level of miR-106b was related to gender, age, tumor size or tumor stage. Also, the results above were verified by analyzing the data of 506 cases from The Cancer Genome Atlas database (TCGA). Conclusions The results pointed out that the high expression of miR-106b-5p serves as an independent factor for predicting the worse prognosis of RCC patients.