A three miRNAs panel in paraffin tissue serves as tool for predicting prognosis of renal cell carcinoma.

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Interpretable multiphasic CT-based radiomic analysis for preoperatively differentiating benign and malignant solid renal tumors: a multicenter study.

BACKGROUND: To develop and compare machine learning models based on triphasic contrast-enhanced CT (CECT) for distinguishing between benign and malignant renal tumors. MATERIALS AND METHODS: In total, 427 patients were enrolled from two medical centers: Center 1 (serving as the training set) and Center 2 (serving as the external validation set). First, 1781 radiomic features were individually extracted from corticomedullary phase (CP), nephrographic phase (NP), and excretory phase (EP) CECT images, after which 10 features were selected by the minimum redundancy maximum relevance method. Second, random forest (RF) models were constructed from single-phase features (CP, NP, and EP) as well as from the combination of features from all three phases (TP). Third, the RF models were assessed in the training and external validation sets. Finally, the internal prediction mechanisms of the models were explained by the SHapley Additive exPlanations (SHAP) approach. RESULTS: A total of 266 patients with renal tumors from Center 1 and 161 patients from Center 2 were included. In the training set, the AUCs of the RF models constructed from the CP, NP, EP, and TP features were 0.886, 0.912, 0.930, and 0.944, respectively. In the external validation set, the models achieved AUCs of 0.860, 0.821, 0.921, and 0.908, respectively. The "original_shape_Flatness" feature played the most important role in the prediction outcome for the RF model based on EP features according to the SHAP method. CONCLUSIONS: The four RF models efficiently differentiated benign from malignant solid renal tumors, with the EP feature-based RF model displaying the best performance.

Erratum: [Corrigendum] miR­216a­5p acts as an oncogene in renal cell carcinoma.

[This corrects the article DOI: 10.3892/etm.2018.5881.].

[Corrigendum] microRNA­181a­5p functions as an oncogene in renal cell carcinoma.

Following the publication of the above article and a corrigendum in 2018 that corrected details of the correspondence information for authors, errors made in Fig. 5 and the funding details (doi: 10.3892/mmr.2018.9117), an interested reader drew to the authors' attention that, in Fig. 6 on p. 8515 showing the results of cell migration and invasion assay experiments, a pair of data panels were overlapping, such that data which were intended to show the results from differently performed experiments appeared to have been derived from the same original source. After having consulted their original data, the authors have realized that Fig. 6 was assembled incorrectly, The revised version of Fig. 6, now showing the correct data for the 'ACHN/migratory/NC' experiment, is shown on the next page. Note that all the authors approve of the publication of this corrigendum, and the authors are grateful to the Editor of Molecular Medicine Reports for granting them the opportunity to publish this. The authors regret their oversight in allowing this error to be included in the paper, and also apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 8510­8517, 2018; DOI: 10.3892/mmr.2018.8899].

Erratum: [Corrigendum] miR­199b­5p serves as a tumor suppressor in renal cell carcinoma.

[This corrects the article DOI: 10.3892/etm.2018.6151.].

A serum panel of three microRNAs may serve as possible biomarkers for kidney renal clear cell carcinoma.

BACKGROUND: Although non-invasive radiological techniques are widely applied in kidney renal clear cell carcinoma (KIRC) diagnosis, more than 50% of KIRCs are detected incidentally during the diagnostic procedures to identify renal cell carcinoma (RCC). Thus, sensitive and accurate KIRC diagnostic methods are required. Therefore, in this study, we aimed to identify KIRC-associated microRNAs (miRNAs). METHODS: This three-phase study included 224 participants (112 each of patients with KIRC and healthy controls (NCs)). RT-qPCR was used to evaluate miRNA expression in KIRC and NC samples. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to predict the usefulness of serum miRNAs in KIRC diagnosis. In addition, we performed survival and bioinformatics analyses. RESULTS: We found that miR-1-3p, miR-129-5p, miR-146b-5p, miR-187-3p, and miR-200a-3p were significantly differentially expressed in patients with KIRC. A panel consisting of three miRNAs (miR-1-3p, miR-129-5p, and miR-146b-5p) had an AUC of 0.895, ranging from 0.848 to 0.942. In addition, using the GEPIA database, we found that the miRNAs were associated with CREB5. According to the survival analysis, miR-146b-5p overexpression was indicative of a poorer prognosis in patients with KIRC. CONCLUSIONS: The identified three-miRNA panel could serve as a non-invasive indicator for KIRC and CREB5 as a potential target gene for KIRC treatment.

Profiling of Serum miRNAs Constructs a Diagnostic 3-miRNA Panel for Clear-Cell Renal Cell Carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) carries significant morbidity and mortality globally with an increasing incidence per year predominantly represented by clear-cell renal cell carcinoma (ccRCC) which accounts for 70-80% of all RCC cases. MicroRNAs(miRNAs) implicate tumor development and progression in epigenetic mechanisms and available profiling of serum miRNAs potentiate them as diagnostic markers for various cancers. MATERIALS AND METHODS: A total of 108 ccRCC patients and 112 normal controls were enrolled. A 3-stage experiment was conducted to identify differentially expressed serum miRNAs in ccRCC and establish a diagnostic miRNAs panel. Additionally, bioinformatic analysis was employed to predict selected miRNAs' target genes, preform functional annotation and explore the roles in ccRCC. RESULTS: MiR-429, miR-10a-5p, miR-154-5p were found to be up-regulated miRNAs. Inversely, miR-27a-3p and miR-221-3p were found to be down-regulated miRNAs. These 5 miRNAs were selected to construct diagnostic panel by backward stepwise logistic regression analysis and ultimately a 3-miRNA panel (miR-429, miR-10a-5p and miR-27a-3p) was established [area under the curve (AUC) = 0.897, sensitivity = 85.0%, specificity = 83.3%]. CONCLUSION: The panel of 3-miRNA holds promise as a novel, convenient, and noninvasive diagnostic method for early detection of ccRCC.

A Panel of Three Serum MicroRNAs as a Potential Diagnostic Biomarker for Urothelial Carcinoma.

OBJECTIVE: Urothelial carcinoma (UCa) is one of the most common malignancies of the genitourinary system, and its early diagnosis is vital to improve the survival of UCa patients. Therefore, novel noninvasive markers are urgently needed to improve the diagnosis of UCa. The present study aims to identify microRNAs (miRNAs) relevant for the diagnosis of UCa. MATERIALS AND METHODS: We enrolled a total of 152 UCa patients and 135 healthy controls at a single institution, between 2012 and 2020. The expression levels of candidate miRNAs were calculated from serum samples based on quantitative reverse transcription-polymerase chain reaction. miRNAs with a good diagnostic value were selected and confirmed step by step in a four-phase test. The area under the curve (AUC) of each miRNA was obtained by analyzing the receiver operating characteristic (ROC) curve, which was used to evaluate the sensitivity, specificity, and corresponding cutoff values of miRNAs. Backward stepwise logistic regression was used to identify a panel of miRNAs that could distinguish UCa from healthy controls. RESULTS: Four miRNAs were relevant for diagnosis: miR17-5p (AUC = 0.786, p < 0.001), miR-125a-5p (AUC = 0.681, p < 0.01), miR145-5p (AUC = 0.737, p < 0.001), and miR-224-5p (AUC = 0.872, p < 0.001). These miRNAs were used to construct a diagnostic panel. The final optimal combination to diagnose UCa included three miRNAs, namely, miR17-5p, miR145-5p, and miR-224-5p. The ROC curve of the panel was constructed, and its AUC was 0.961 (95% CI: 0.931-0.991; sensitivity = 93.8%, and specificity = 87.5%). CONCLUSION: In this study, we discovered four miRNAs (miR17-5p, miR-125a-5p, miR145-5p, and miR-224-5p) that were relevant for UCa diagnosis, and successfully developed a panel using three of these miRNAs. This panel may serve as a new biomarker tool with high sensitivity and specificity to diagnose UCa in patients.

A four-microRNA panel in serum may serve as potential biomarker for renal cell carcinoma diagnosis.

Background: Renal cell carcinoma (RCC) is one out of the most universal malignant tumors globally, and its incidence is increasing annually. MicroRNA (miRNA) in serum could be considered as a non-invasive detecting biomarker for RCC diagnosis. Method: A total of 224 participants (112 RCC patients (RCCs) and 112 normal controls (NCs)) were enrolled in the three-phrase study. Reverse transcription quantitative PCR (RT-qPCR) was applied to reveal the miRNA expression levels in RCCs and NCs. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were utilized to predict the diagnostic ability of serum miRNAs for RCC. Bioinformatic analysis and survival analysis were also included in our study. Results: Compared to NCs, the expression degree of miR-155-5p, miR-224-5p in serum was significantly upregulated in RCC patients, and miR-1-3p, miR-124-3p, miR-129-5p, and miR-200b-3p were downregulated. A four-miRNA panel was construed, and the AUC of the panel was 0.903 (95% CI: 0.847-0.944; p < 0.001; sensitivity = 75.61%, specificity = 93.67%). Results from GEPIA database indicated that CHL1, MPP5, and SORT1 could be seen as promising target genes of the four-miRNA panel. Survival analysis of candidate miRNAs manifested that miR-155-5p was associated with the survival rate of RCC significantly. Conclusions: The four-miRNA panel in serum has a great potential to be non-invasive biomarkers for RCC sift to check.

Combination of tumor suppressor miR-20b-5p, miR-30a-5p, and miR-196a-5p as a serum diagnostic panel for renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) accounts for 3 % of cancer patients. Early detection influences the therapeutic strategy and significantly improves patients' survival rates. Stable existing circulating miRNAs could be a promising diagnostic biomarker. METHODS: Previously our team demonstrated the anti-tumor effect of miR-20b-5p, miR-30a-5p and miR-196a-5p in RCC tissue and cell lines. Here, based on 110 RCC patients and 110 health control, we investigated serum expression of these three miRNAs in the testing set and the validation set separately by using quantitative real-time PCR. A three-miRNA panel with high diagnostic efficiency was constructed. Correlations between these miRNAs and clinical parameters were investigated. Additionally, the TCGA dataset and bioinformatic analysis are used for the functional exploration of these miRNAs. RESULTS: Serum expression levels of miR-20b-5p, miR-30a-5p were significantly reduced in RCC patients, while miR-196a-5p expression level was up-regulated (p < 0.001). miR-20b-5p, miR-30a-5p and miR-196a-5p had moderate diagnostic ability for RCC (AUC = 0.807, 0.766 and 0.719 in the testing set, respectively). The AUC of the three-miRNA panel was 0.949 in the testing set and 0.938 in the validation set. Specifically, the serum expression level of miR-196a-5p was significantly down-regulated in RCC patients with higher Fuhrman grade (p = 0.051). TCGA dataset analysis showed that the three-miRNA panel probably participated in RCC by targeting ITGA4 and NRP2. CONCLUSION: The three-miRNA panel could serve as a promising non-invasive biomarker for RCC detection.

Tumor suppressor miR-33b-5p regulates cellular function and acts a prognostic biomarker in RCC.

BACKGROUND: Renal cell carcinoma (RCC) is a renal parenchyma neoplasm with a 30% recurrence rate even when treated properly. MicroRNAs are noncoding small RNAs that are involved in cellular communication and may participate in cancer development. This study aimed to explore the relationship between miR-33b-5p expression and RCC progression and prognosis. METHOD: RT-qPCR, CCK-8 assay, wound scratch assay, transwell assay and flow cytometry assay were used to evaluate the expression and function of miR-33b-5p in RCC. Additionally, RCC samples and survival data from The Cancer Genome Atlas were used to analyze the prognostic functions of miR-33b-5p. RESULTS: miR-33b-5p expression in RCC tissues and cell lines (786-O, ACHN) were found to be significantly downregulated, compared with normal tissues and cell lines (P<0.001). The miR-33b-5p mimic transfected cells showed a slower proliferation rate (P<0.01), while its invasion ability decreased by 38.16% (786-O, P<0.001) and 49.19% (ACHN, P<0.05), compared with the negative control (NC). The migration ability of both RCC lines were found to be as follows: miR-33b-5p inhibitor > NC or NC inhibitor > miR-33b-5p mimic. Additionally, TCGA and RCC samples reveal that low miR-33b-5p expression is related to poor survival outcomes (univariate analysis, P=0.029; multivariate analysis, P=0.024; Kaplan-Meier survival curves, P=0.014). Target genes prediction suggests that miR-33b-5p performs its tumor-suppressive effects and prognostic role through targeting TBX15, SLC12A5, and PTGFRN. CONCLUSIONS: miR-33b-5p may function as a tumor-suppressive regulator and prognostic biomarker in RCC.

Identification of a four-microRNA panel in serum as promising biomarker for colorectal carcinoma detection.

Background: Screening for colorectal carcinoma (CRC) lacks an efficient, inexpensive and noninvasive approach. The stable presence of serum miRNA is expected to become a new diagnostic marker. Materials & methods: Based on 135 CRC patients and 135 normal controls, this study was conducted in three phases to identify suitable serum miRNA for CRC diagnosis by using quantitative reverse transcription PCR. Bioinformatic assays were used for target genes prediction and functional annotation. Results: Serum expression level of seven miRNAs were significantly different between CRC patients and the normal controls. The final diagnostic panel (area under the curve = 0.893; sensitivity = 81.25%, specificity = 73.33%) consists of miR-203a-3p, miR-145-5p, miR-375-3p and miR-200c-3p. Conclusion: The four-miRNA panel may serve as a novel, noninvasive biomarker for CRC diagnosis and screening.

A Three-microRNA Panel in Serum: Serving as a Potential Diagnostic Biomarker for Renal Cell Carcinoma.

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.

miR-625-3p promotes migration and invasion and reduces apoptosis of clear cell renal cell carcinoma.

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.

True hermaphroditism with seminoma: A case report.

The aim of the present study was to discuss the diagnosis and treatment of a patient with true hermaphroditism complicated by seminoma. The patient was a 35-year-old man who was admitted to the Peking University Shenzhen Hospital with a retractable mass in the left inguinal region for 20 years. A computed tomography examination revealed right cryptorchidism. The postoperative pathology suggested true hermaphroditism with a seminoma. The results of immunohistochemical examination were as follows: Sal-like protein 4+ (partially weak); octamer-binding transcription factor 4+ (partially weak); CD117+; cytokeratin+; CD30-, α-fetoprotein-, inhibin-α-. The karyotype was 46, XY. Adult true hermaphroditism combined with seminoma is rare in clinical practice. Combined histopathological analysis, immunophenotype detection and karyotype analysis are of great value in the diagnosis and differential diagnosis. Early intervention and combined surgery with radiotherapy and chemotherapy can significantly improve the prognosis of such patients.

Primary adrenal teratoma: A case series and review of the literature.

Primary adrenal teratoma is a rare type of cancer. Of the 338 patients who underwent adrenalectomy during this study, only 2 (aged 69 and 29 years) were diagnosed with adrenal teratoma and underwent laparoscopic retroperitoneal adrenalectomy. For the purposes of the present study, the term 'adrenal teratoma' was searched in the PubMed database, and 237 articles published between June 1952 and March 2017 were retrieved. However, we were only able to identify 10 relevant studies. In total, these studies reported a series of 18 cases of primary adrenal teratoma in patients aged >16 years, another 8 cases of adult adrenal retroperitoneal teratoma, and 7 cases of adrenal teratoma in children aged <16 years. In the 18 cases aged >16 years, the age range was 17-61 years (mean ± standard deviation, 33.06±15.47 years), the median tumor diameter was 8.25 cm and 13 patients (72.22%) were female. Almost all patients underwent laparoscopic surgery between 2006 and 2017 (75%). Among the 7 cases of adrenal teratoma in children under the age of 16 years, 5 cases (71.43%) were male, the median tumor diameter was 10 cm, the oldest patient was aged 8 years, 5 cases (71.43%) were selected for open surgical resection of the tumor, and 5 cases (71.43%) were followed up without recurrence or death. These data indicate that primary adrenal teratomas in children are rarer compared with adults. Although the data are limited, it was observed that the clinical symptoms of primary adrenal teratoma are not typical, the preferred treatment is retroperitoneal laparoscopic surgery, and the prognosis is favorable. The aim of the present study was to elucidate the clinical characteristics associated with primary adrenal teratoma, in order to further raise awareness of this rare disease.

Erratum: miR-199b-5p serves as a tumor suppressor in renal cell carcinoma.

[This corrects the article DOI: 10.3892/etm.2018.6151.].

Erratum: Adrenal collision tumor (parachordoma and ganglioneuroma): A case report.

[This corrects the article DOI: 10.3892/mco.2018.1610.].

Oncogenic miR-425-5p is associated with cellular migration, proliferation and apoptosis in renal cell carcinoma.

An increasing number of studies have demonstrated the function of microRNAs (miRNAs) in the initiation and development of various types of cancer. Among them, miR-425-5p is proven to serve an important function in several types of cancer, including gastric, cervical cancer, and hepatocellular carcinoma. However, the function of miR-425-5p in renal cell carcinoma (RCC) remains unclear. In the present study, it was demonstrated that the expression level of miR-425-5p was upregulated in RCC tissues and cell lines compared with normal tissues and cell lines (P<0.05). Additionally, Cell Counting kit-8 and MTT assays were employed to assess cell viability and proliferation, whereas wound healing and Transwell assays were employed to examine migration and invasion. The results demonstrated that upregulation of miR-425-5p promoted cell viability and the invasion and migration of ACHN and 786O cells (P<0.05). Flow cytometric analysis confirmed that upregulation of miR-425-5p inhibited apoptosis of ACHN and 786O cells (P<0.05). Downregulation of miR-425-5p inhibited the viability and invasion and migration of ACHN and 786O cells (P<0.05). In the present study, upregulation of miR-425-5p inhibited apoptosis of ACHN and 786O cells whereas no differences in early apoptotic rate were observed between the inhibitor and inhibitor NC groups for 786O and ACHN cells. These results indicate that miR-425-5p may act as an oncogene in RCC.

miR-199b-5p serves as a tumor suppressor in renal cell carcinoma.

MicroRNA (miR)-199b-5p has been reported to have a critical role in various types of malignancy. However, the exact function miR-199b-5p in renal cancer remains to be fully elucidated. The present study aimed to detect the expression levels of miR-199b-5p in renal cell carcinoma (RCC) tissues and RCC cell lines, and investigated the effect of miR-199b-5p in vitro with Cell Counting Kit-8, MTT, scratch wound, Transwell and flow cytometric assays. The results demonstrated that the expression levels of miR-199b-5p were significantly downregulated in RCC tissues and cell lines compared with those in paired adjacent normal renal tissues and a reference cell line, respectively. Downregulation of miR-199b-5p by transfection with a synthetic inhibitor promoted cellular proliferation and migration, while reducing the apoptotic rate, indicating that miR-199b-5p may serve as a tumor suppressor in RCC. Further study is required to identify target genes of miR-199b-5p to elucidate the mechanisms underlying the role of miR-199b-5p in the occurrence and development of RCC.