Co-transcriptional R-loops-mediated epigenetic regulation drives growth retardation and docetaxel chemosensitivity enhancement in advanced prostate cancer.

R-loops are prevalent three-stranded nucleic acid structures, comprising a DNA-RNA hybrid and a displaced single-stranded DNA, that frequently form during transcription and may be attributed to genomic stability and gene expression regulation. It was recently discovered that RNA modification contributes to maintain the stability of R-loops such as N6-methyladenosine (m6A). Yet, m6A-modified R-loops in regulating gene transcription remains poorly understood. Here, we demonstrated that insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) recognize R-loops in an m6A-dependent way. Consequently, IGF2BPs overexpression leads to increased overall R-loop levels, cell migration inhibition, and cell growth retardation in prostate cancer (PCa) via precluding the binding of DNA methyltransferase 1(DNMT1) to semaphorin 3 F (SEMA3F) promoters. Moreover, the K homology (KH) domains of IGF2BPs are required for their recognition of m6A-containing R-loops and are required for tumor suppressor functions. Overexpression of SEMA3F markedly enhanced docetaxel chemosensitivity in prostate cancer via regulating Hippo pathway. Our findings point to a distinct R-loop resolution pathway mediated by IGF2BPs, emphasizing the functional importance of IGF2BPs as epigenetic R-loop readers in transcriptional genetic regulation and cancer biology.The manuscript summarizes the new role of N6-methyladenosine in epigenetic regulation, we introduce the distinct R-loop resolution mediated by IGF2BP proteins in an m6A-dependent way, which probably lead to the growth retardation and docetaxel chemotherapy resistance in prostate cancer. Moreover, our findings first emphasized the functional importance of IGF2BPs as epigenetic R-loop readers in transcriptional genetic regulation and cancer biology. In addition, our research provides a novel RBM15/IGF2BPs/DNMT1 trans-omics regulation m6A axis, indicating the new crosstalk between RNA m6A methylation and DNA methylation in prostate cancer.

Hypermethylated TAGMe as a universal-cancer-only methylation marker and its application in diagnosis and recurrence monitoring of urothelial carcinoma.

BACKGROUND: Urothelial carcinoma (UC) is the second most common urological malignancy. Despite numerous molecular markers have been evaluated during the past decades, no urothelial markers for diagnosis and recurrence monitoring have shown consistent clinical utility. METHODS: The methylation level of tissue samples from public database and clinical collected were analyzed. Patients with UC and benign diseases of the urinary system (BUD) were enrolled to establish TAGMe (TAG of Methylation) assessment in a training cohort (n = 567) using restriction enzyme-based bisulfite-free qPCR. The performance of TAGMe assessment was further verified in the validation cohort (n = 198). Urine samples from 57 UC patients undergoing postoperative surveillance were collected monthly for six months after surgery to assess the TAGMe methylation. RESULTS: We identified TAGMe as a potentially novel Universal-Cancer-Only Methylation (UCOM) marker was hypermethylated in multi-type cancers and investigated its application in UC. Restriction enzyme-based bisulfite-free qPCR was used for detection, and the results of which were consistent with gold standard pyrosequencing. Importantly, hypermethylated TAGMe showed excellent sensitivity of 88.9% (95% CI: 81.4-94.1%) and specificity of 90.0% (95% CI: 81.9-95.3%) in efficiently distinguishing UC from BUD patients in urine and also performed well in different clinical scenarios of UC. Moreover, the abnormality of TAGMe as an indicator of recurrence might precede clinical recurrence by three months to one year, which provided an invaluable time window for timely and effective intervention to prevent UC upstaging. CONCLUSION: TAGMe assessment based on a novel single target in urine is effective and easy to perform in UC diagnosis and recurrence monitoring, which may reduce the burden of cystoscopy. Trial registration ChiCTR2100052507. Registered on 30 October 2021.

Mendelian randomization analysis reveals fresh fruit intake as a protective factor for urolithiasis.

OBJECTIVE: Previous studies have proposed that food intakes are associated with the risk of urolithiasis. Here, we conducted a two-sample Mendelian randomization (MR) study to evaluate the causal effects of different food intakes on urolithiasis. METHODS: Independent genetic variants associated with different food intakes at a genome-wide significant level were selected from summary-level statistics of genome-wide association studies from the UK Biobank. The association of these instrumental variables with urolithiasis was studied in a cohort from FinnGen Consortium. RESULTS: Among the 15 studied food intake exposures, tea intake (odds ratio [OR] = 0.433, 95% confidence interval [CI] = 0.281-0.667, p value = 1.470 × 10-4) and fresh fruit intake (OR = 0.358, 95% CI = 0.185-0.694, p value = 0.002) were found to significantly reduce the risk of the calculus of kidney and ureter. The association remained consistent in the sensitivity analyses. After adjusting for the effects of vitamin D and vitamin C, fresh fruit intake remained the reverse causal association with the calculus of kidney and ureter. CONCLUSIONS: Genetically proxied fresh fruit intake is causally associated with a reduced risk of the calculus of kidney and ureter.

Risk factor analysis and optimal cutoff value selection of PSAD for diagnosing clinically significant prostate cancer in patients with negative mpMRI: results from a high-volume center in Southeast China.

BACKGROUND: Multi-parametric magnetic resonance imaging (mpMRI) is a diagnostic tool used for screening, localizing, and staging prostate cancer. Patients with Prostate Imaging Reporting and Data System (PI-RADS) score of 1 and 2 are considered negative mpMRI, with a lower likelihood of detecting clinically significant prostate cancer (csPCa). However, relying solely on mpMRI is insufficient to completely exclude csPCa, necessitating further stratification of csPCa patients using biomarkers. METHODS: A retrospective study was conducted on mpMRI-negative patients who underwent prostate biopsy at the First Affiliated Hospital of Zhejiang University from January 2022 to June 2023. A total of 607 patients were included based on inclusion and exclusion criteria. Univariate and multivariate logistic regression analysis were performed to identify risk factors for diagnosing csPCa in patients with negative mpMRI. Receiver Operating Characteristic (ROC) curves were plotted to compare the discriminatory ability of different Prostate-Specific Antigen Density (PSAD) cutoff values for csPCa. RESULTS: Among the 607 patients with negative mpMRI, 73 patients were diagnosed with csPCa. In univariate logistic regression analysis, age, PSA, f/tPSA, prostate volume, and PSAD were all associated with diagnosing csPCa in patients with negative mpMRI (P < 0.05), with PSAD being the most accurate predictor. In multivariate logistic regression analysis, f/tPSA, age, and PSAD were independent predictors of csPCa (P < 0.05). PSAD cutoff value of 0.20 ng/ml/ml has better discriminatory ability for predicting csPCa and is a significant risk factor for csPCa in multivariate analysis. CONCLUSION: Age, f/tPSA, and PSAD are independent predictors of diagnosing csPCa in patients with negative mpMRI. It is suggested that patients with negative mpMRI and PSAD less than 0.20 ng/ml/ml could avoid prostate biopsy, as a PSAD cutoff value of 0.20 ng/ml/ml has better diagnostic performance than the traditional cutoff value of 0.15 ng/ml/ml.

A prospective multi-center randomized comparative trial evaluating outcomes of transrectal ultrasound (TRUS)-guided 12-core systematic biopsy, mpMRI-targeted 12-core biopsy, and artificial intelligence ultrasound of prostate (AIUSP) 6-core targeted biopsy for prostate cancer diagnosis.

BACKGROUND: Artificial intelligence ultrasound of prostate (AIUSP)-targeted biopsy has been used for prostate cancer (PCa) diagnosis. The objective of this prospective multi-center head-to-head clinical randomized comparative trail (RCT) is to compare PCa detection rate in the TRUS-guided 12-core standard systematic biopsy (TRUS-SB) group and cognitive fused mpMRI-guided 12-core biopsy (mpMRI) group against AIUSP group. METHODS: Four hundred patients were randomized to three arms and underwent biopsies by TRUS-SB (n = 133), mpMRI (n = 134), and AIUSP (n = 133) between January 2015 and December 2017. In TRUS-SB group, a standard 12-core systematic biopsy was performed. In mpMRI group, mpMRI-suspicious lesions (PI-RADS 3-5) were targeted by 2-core biopsy followed by a 10-core systematic biopsy. Otherwise, 12-core systematic biopsy was performed. In AIUSP group, a 6-core targeted biopsy was performed. The primary endpoint was PCa detection rate. RESULTS: AIUSP detected the highest rate of PCa (66/133, 49.6%) compared to TRUS-SB (46/133, 34.6%, p = 0.036) and mpMRI (48/134, 35.8%, p = 0.052). Compared to TRUS-SB (35/133, 26.3%) and mpMRI (31/134, 23.1%) groups, clinically significant PCa (csPCa) detection rate was 32.3% (43/133) in AIUSP group. Overall biopsy core positive rate in the TRUS-SB group (11.0%, 176/1598) and in the mpMRI group (12.7%, 204/1608) was significantly lower than that in the AIUSP group (22.7%, 181/798, p < 0.001). CONCLUSIONS: AIUSP detected the highest rate of overall and significant PCa compared to TRUS-SB and mpMRI, and could be used as an alternative to systematic biopsy in the future. REGISTRATION: This trial was registered in ISRCTN (ISRCTN18033113).

The role of HIF in angiogenesis, lymphangiogenesis, and tumor microenvironment in urological cancers.

Typically associated with solid tumors, hypoxia contributes to tumor angiogenesis and lymphangiogenesis through various molecular mechanisms. Accumulating studies indicate that hypoxia-inducible factor is the key transcription factor coordinating endothelial cells to respond to hypoxia in urological cancers, mainly renal cell carcinoma, prostate cancer, and bladder cancer. Moreover, it has been suggested that tumor hypoxia in tumor microenvironment simultaneously recruits stromal cells to suppress immune activities. This review summarizes the mechanisms by which HIF regulates tumorigenesis and elaborates on the associations between HIF and angiogenesis, lymphangiogenesis, and tumor microenvironment in urological cancers.

Complex impact of DNA methylation on transcriptional dysregulation across 22 human cancer types.

Accumulating evidence has demonstrated that transcriptional regulation is affected by DNA methylation. Understanding the perturbation of DNA methylation-mediated regulation between transcriptional factors (TFs) and targets is crucial for human diseases. However, the global landscape of DNA methylation-mediated transcriptional dysregulation (DMTD) across cancers has not been portrayed. Here, we systematically identified DMTD by integrative analysis of transcriptome, methylome and regulatome across 22 human cancer types. Our results revealed that transcriptional regulation was affected by DNA methylation, involving hundreds of methylation-sensitive TFs (MethTFs). In addition, pan-cancer MethTFs, the regulatory activity of which is generally affected by DNA methylation across cancers, exhibit dominant functional characteristics and regulate several cancer hallmarks. Moreover, pan-cancer MethTFs were found to be affected by DNA methylation in a complex pattern. Finally, we investigated the cooperation among MethTFs and identified a network module that consisted of 43 MethTFs with prognostic potential. In summary, we systematically dissected the transcriptional dysregulation mediated by DNA methylation across cancer types, and our results provide a valuable resource for both epigenetic and transcriptional regulation communities.

Global pattern and drivers of water scarcity research: a combined bibliometric and geographic detector study.

Water scarcity, which refers to a deficit of freshwater resources availability in meeting anthropogenic and environmental water needs, is nowadays a growing concern in many countries around the world. Because water scarcity is often poor management induced, research is critical to advance knowledge and provide technical and policy support for water scarcity adaptation and solutions. Here, we address global water scarcity research pattern and underlying drivers, using the bibliometric analysis combined with geographic detector. The results indicate that water scarcity research exhibits great temporal and spatial variations. Predominant factors that control the numbers of water scarcity publications are gross domestic products (GDP) and population, which altogether explain 30-52% of the variance of the number of publications in different countries. Water scarcity research is biased in a few populated and affluent countries. Other factors, including physical water scarcity, research and development expenditure, and governance indicators can also be linked to water scarcity research. Keywords mining reveals that hotspots of research domains on causes, approaches, types, and effects of water scarcity show continental difference. The results have policy implications for guiding future water scarcity research. Research in developing countries suffering from physical and economic water scarcity should be enhanced to improve adaptive capacity and reduce vulnerability to water scarcity.

[Analysis of CiteSpace knowledge map for traditional Chinese medicine prevention and treatment of cerebral small vessel diseases].

This study aims to analyze the research on the prevention and treatment of cerebral small vessel diseases(CSVDs) with traditional Chinese medicine(TCM) based on knowledge map, and to preliminarily explore the research hotspots and trends. To be specific, articles on TCM treatment of CSVDs in CNKI, Wanfang, and VIP(from establishment to November 2021) were retrieved, followed by bibliometric analysis. Then CiteSpace 5.7 R4 and Gephi were employed for generation of maps on annual number of articles, author cooperation, institution cooperation, keyword co-occurrence, keyword clustering, and keyword emergence. A total of 106 eligible articles were screened out, and the annual number of articles presented a steady upward trend. A total of 277 authors were included in the author cooperation network, among whom CHEN Zhigang published the most articles. A total of 87 institutions were included in the institution cooperation network, among which Dongfang Hospital of Beijing University of Chinese Medicine showed the most frequent cooperation with other institutions. Keyword clustering showed that research on the TCM treatment of CSVDs mainly focused on five aspects: related disease research, neurological function deficits, disease nature and location in TCM, TCM treatment methods, and formulas. The prevention and treatment of CSVDs with TCM in China has been developing steadily in the past ten years, and TCM has unique advantages in the prevention and treatment of this disease. The knowledge maps vividly demonstrated the development and research hotspots and trends in this field. The result is expected to provide a reference for further research in this field.

Upregulation of ARNTL2 is associated with poor survival and immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) is a member of the PAS superfamily. Previous studies explored the carcinogenic roles of transcription factor ARNTL2 in human malignancies. However, its roles in ccRCC have not been elucidated. This study sought to explore the roles of ARNTL2 in ccRCC and determine its correlations with tumor immunity. METHODS: The expression of ARNTL2 was analyzed using the GEO, TCGA and GTEx database, and verified in ccRCC tissue samples and cell lines by qRT-PCR and western blot analysis. Kaplan-Meier survival curve analysis, Cox regression analysis (including univariate and multivariate analysis) was utilized to evaluate the prognostic values of ARNTL2. Potential biological mechanisms of ARNTL2 were explored using GSEA method. Colony formation and wound healing assays were conducted to explore the oncogenic role of ARNTL2 in ccRCC. ssGSEA and xCell algorithm were used to explore the correlation between ARNTL2 expression and tumor immune microenvironment (TIME). RESULTS: ARNTL2 was significantly upregulated in ccRCC tissues and cell lines compared to normal kidney tissues and cell line. Enhanced expression of ARNTL2 was strongly linked to advanced clinical stage and unfavorable overall survival in ccRCC. ARNTL2 was determined as an independent prognostic marker through cox regression analysis. A prognostic nomogram was constructed to predict 1-, 3- and 5-year overall survival of ccRCC patients by integrating ARNTL2 expression with other clinicopathologic variables. GSEA analysis showed that focal adhesion, T cell receptor, cell cycle, and JAK-STAT signaling pathway were significantly enriched in high ARNTL2 samples. Silencing of ARNTL2 suppressed the colony formation ability and wound healing efficacy of ccRCC cell lines. xCell analysis showed that high expression level of ARNTL2 exhibited an immune infiltration status similar to CD8 + inflamed ccRCC subtype, which was characterized by high infiltration level of CD8 + T cell and high expression level of the immune escape biomarkers such as PD-L1, PD-L2, PD1 and CTLA4. CONCLUSION: ARNTL2 is an independent adverse predictor of ccRCC patient survival. High expression level of ARNTL2 is associated with immune infiltration, and may be a novel therapeutic target in ccRCC.

Antitumor Activity of Small Activating RNAs Induced PAWR Gene Activation in Human Bladder Cancer Cells.

Small double-stranded RNAs (dsRNAs) have been proved to effectively up-regulate the expression of particular genes by targeting their promoters. These small dsRNAs were also termed small activating RNAs (saRNAs). We previously reported that several small double-stranded RNAs (dsRNAs) targeting the PRKC apoptosis WT1 regulator (PAWR) promoter can up-regulate PAWR gene expression effectively in human cancer cells. The present study was conducted to evaluate the antitumor potential of PAWR gene induction by these saRNAs in bladder cancer. Promisingly, we found that up-regulation of PAWR by saRNA inhibited the growth of bladder cancer cells by inducing cell apoptosis and cell cycle arrest which was related to inhibition of anti­apoptotic protein Bcl-2 and inactivation of the NF-κB and Akt pathways. The activation of the caspase cascade and the regulation of cell cycle related proteins also supported the efficacy of the treatment. Moreover, our study also showed that these saRNAs cooperated with cisplatin in the inhibition of bladder cancer cells. Overall, these data suggest that activation of PAWR by saRNA may have a therapeutic benefit for bladder cancer.

METTL3/YTHDF2 m6 A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer.

N6-Methyladenosine (m6 A) modification, the most prevalent modification of eukaryotic messenger RNA (mRNA), is involved in the progression of various tumours. However, the specific role of m6 A in bladder cancer (BCa) is still poorly understood. In this study, we demonstrated the tumour-promoting function and specific regulatory mechanism of m6 A axis, consisting of the core 'writer' protein METTL3 and the major reader protein YTHDF2. Depletion of METTL3 impaired cancer proliferation and cancer metastasis in vitro and in vivo. Through transcriptome sequencing, m6 A methylated RNA immunoprecipitation (MeRIP) and RIP, we determined that the METTL3/YTHDF2 m6 A axis directly degraded the mRNAs of the tumour suppressors SETD7 and KLF4, contributing to the progression of BCa. In addition, overexpression of SETD7 and KLF4 revealed a phenotype consistent with that induced by depletion of the m6 A axis. Thus, our findings on the METTL3/YTHDF2/SETD7/KLF4 m6 A axis provide the insight into the underlying mechanism of carcinogenesis and highlight potential therapeutic targets for BCa.

YTHDF2 mediates the mRNA degradation of the tumor suppressors to induce AKT phosphorylation in N6-methyladenosine-dependent way in prostate cancer.

BACKGROUND: N6-methyladenosine (m6A) is the most abundant modification in mRNA of humans. Emerging evidence has supported the fact that m6A is comprehensively involved in various diseases especially cancers. As a crucial reader, YTHDF2 usually mediates the degradation of m6A-modified mRNAs in m6A-dependent way. However, the function and mechanisms of m6A especially YTHDF2 in prostate cancer (PCa) still remain elusive. METHODS: To investigate the functions and mechanisms of YTHDF2 in PCa, in vitro, in vivo biofunctional assays and epigenetics experiments were performed. Endogenous expression silencing of YTHDF2 and METTL3 was established with lentivirus-based shRNA technique. Colony formation, flow cytometry and trans-well assays were performed for cell function identifications. Subcutaneous xenografts and metastatic mice models were combined with in vivo imaging system to investigate the phenotypes when knocking down YTHDF2 and METTL3. m6A RNA immunoprecipitation (MeRIP) sequencing, mRNA sequencing, RIP-RT-qPCR and bioinformatics analysis were mainly used to screen and validate the direct common targets of YTHDF2 and METTL3. In addition, TCGA database was also used to analyze the expression pattern of YTHDF2, METTL3 and the common target LHPP in PCa, and their correlation with clinical prognosis. RESULTS: The upregulated YTHDF2 and METTL3 in PCa predicted a worse overall survival rate. Knocking down YTHDF2 or METTL3 markedly inhibited the proliferation and migration of PCa in vivo and in vitro. LHPP and NKX3-1 were identified as the direct targets of both YTHDF2 and METTL3. YTHDF2 directly bound to the m6A modification sites of LHPP and NKX3-1 to mediate the mRNA degradation. Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and NKX3-1 at both mRNA and protein level with inhibited phosphorylated AKT. Overexpression of LHPP and NKX3-1 presented the consistent phenotypes and AKT phosphorylation inhibition with knock-down of YTHDF2 or METTL3. Phosphorylated AKT was consequently confirmed as the downstream of METTL3/YTHDF2/LHPP/NKX3-1 to induce tumor proliferation and migration. CONCLUSION: We propose a novel regulatory mechanism in which YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer. We hope our findings may provide new concepts of PCa biology.

Dual regulatory role of CCNA2 in modulating CDK6 and MET-mediated cell-cycle pathway and EMT progression is blocked by miR-381-3p in bladder cancer.

Emerging evidence has elucidated that microRNAs (miRNAs) transcribed from miRNA cluster at DLK-DIO3 imprinted domain are involved in various cancers. However, as one member of this cluster, the underlying mechanisms and functions of miR-381-3p in bladder cancer (BCa) still remains elusive. Here we demonstrate that the hypermethylated status of upstream maternally expressed gene 3 divergent methylation region reduces the expression of miR-381-3p in BCa by bisulfite-sequencing PCR. In vitro and in vivo experiments indicate that overexpression of miR-381-3p significantly inhibits cell proliferation via inducing G1 phase arrest and migration via down-regulating MET and CCNA2 induced EMT progression. CDK6/CCNA2/MET are all identified as the direct targets of miR-381-3p by bioinformatics analysis and dual-luciferase reporter assay. Furthermore, inhibition of CCNA2 mediated by miR-381-3p as the crucial biregulator not only participates in the proliferation regulation with CDK6 in cell cycle but also modulates the EMT progression via ROCK/AKT/ß-catenin/SNAIL pathway, which establishes an EMT circuit combined with miR-381-3p/MET/AKT/GSK-3ß/SNAIL pathway, and SNAIL is the last confocal target to induce EMT progression. To conclude, we propose 2 novel regulatory circuits mediated by miR-381-3p in BCa, which may assist in the development of more effective therapies against BCa in the future.-Li, J., Ying, Y., Xie, H., Jin, K., Yan, H., Wang, S., Xu, M., Xu, X., Wang, X., Yang, K., Zheng, X., Xie, L. Dual regulatory role of CCNA2 in modulating CDK6 and MET-mediated cell-cycle pathway and EMT progression is blocked by miR-381-3p in bladder cancer.

LncMAP: Pan-cancer atlas of long noncoding RNA-mediated transcriptional network perturbations.

Gene regulatory network perturbations contribute to the development and progression of cancer, however, molecular determinants that mediate transcriptional perturbations remain a fundamental challenge for cancer biology. We show that transcriptional perturbations are widely mediated by long noncoding RNAs (lncRNAs) via integration of genome-wide transcriptional regulation with paired lncRNA and gene expression profiles. Systematic construction of an LncRNA Modulator Atlas in Pan-cancer (LncMAP) reveals distinct types of lncRNA regulatory molecules, which are expressed in multiple tissues, exhibit higher conservation. Strikingly, cancers with similar tissue origin share lncRNA modulators which perturb the regulation of cell cycle and immune response-related functions. Furthermore, we identified a large number of pan-cancer lncRNA modulators with potential clinical significance, which are differentially expressed in cancer or are strongly correlated with drug sensitivity across cell lines. Further stratification of cancer patients based on lncRNA-mediated transcriptional perturbations identifies subtypes with distinct survival rates. Finally, we made a user-friendly web interface available for exploring lncRNA-mediated transcriptional perturbations across cancer types. Our study provides a systems-level dissection of lncRNA-mediated regulatory perturbations in cancer, and also presents a valuable tool and resource for investigating the function of lncRNAs in cancer.

[Application of artificial intelligence combined with multi-parametric MRI in the early diagnosis of prostate cancer].

OBJECTIVE: To explore the value of artificial intelligence combined with multi-parametric MRI (AI-mpMRI) in the early diagnosis of prostate cancer. METHODS: This retrospective study included 64 cases of prostate cancer confirmed by biopsy and treated by radical prostatectomy from May 2017 to February 2018. The mpMRI images of T2 weighted imaging (T2WI), diffusion weighted imaging (DWI) and dynamic-contrast enhanced (DCE) MRI and the pathological sections corresponding to the three sequential MRI images were collected. The benign and malignant regions were labeled on the pathological slice level, the three sequential MRI axial images at the same level were virtually covered with the pathological slice using computer-aided transparent mapping technology, and selected the fixed-sized benign and malignant regions of interest (ROI). The MATLAB software was used to display the features of the images and screen out the characteristic parameters with P < 0.05, so as to derive high-accuracy analytical methods for the diagnosis of prostate cancer. RESULTS: A total of 31 image characteristics were extracted with the MATLAB software, and 3 high-accuracy analytical methods screened out for the diagnosis of prostate cancer, including the linear discrimination, logistic regression analysis, and support vector machine classification, with the accuracy rates of 75.9%, 75.4% and 74.9% and the areas under the curve (AUC) of 0.83, 0.82 and 0.82, respectively. CONCLUSIONS: AI-mpMRI can achieve a high detection rate in the early diagnosis of prostate cancer and therefore has a high clinical application value.

Transperineal versus transrectal prostate biopsy in the diagnosis of prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Because conventional prostate biopsy has some limitations, optimal variations of prostate biopsy strategies have emerged to improve the diagnosis rate of prostate cancer. We conducted the systematic review to compare the diagnosis rate and complications of transperineal versus transrectal prostate biopsy. We searched for online publications published through June 27, 2018, in PubMed, Scopus, Web of Science, and Chinese National Knowledge Infrastructure databases. The relative risk and 95% confidence interval were utilized to appraise the diagnosis and complication rate. The condensed relative risk of 11 included studies indicated that transperineal prostate biopsy has the same diagnosis accuracy of transrectal prostate biopsy; however, a significantly lower risk of fever and rectal bleeding was reported for transperineal prostate biopsy. No clue of publication bias could be identified. SHORT CONCLUSION: To conclude, this review indicated that transperineal and transrectal prostate biopsy have the same diagnosis accuracy, but the transperineal approach has a lower risk of fever and rectal bleeding. More studies are warranted to confirm these findings and discover a more effective diagnosis method for prostate cancer.

The dual role of N6-methyladenosine modification of RNAs is involved in human cancers.

As the most abundant and reversible RNA modification in eukaryotic cells, m6 A triggers a new layer of epi-transcription. M6 A modification occurs through a methylation process modified by "writers" complexes, reversed by "erasers", and exerts its role depending on various "readers". Emerging evidence shows that there is a strong association between m6 A and human diseases, especially cancers. Herein, we review bi-aspects of m6 A in regulating cancers mediated by the m6 A-associated proteins, which exert vital and specific roles in the development of various cancers. Generally, the m6 A modification performs promotion or inhibition functions (dual role) in tumorigenesis and progression of various cancers, which suggests a new concept in cancer regulations. In addition, m6 A-targeted therapies including competitive antagonists of m6 A-associated proteins may provide a new tumour intervention in the future.

MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathway.

BACKGROUND: Current evidence indicates that miR-608 is widely down-regulated in various malignant tumors including liver cancer, colon cancer, lung cancer and glioma, and acts as a tumor suppressor by inhibiting cell proliferation, invasion and migration or by promoting apoptosis. The specific biological function of miR-608 in bladder cancer is still unknown. METHODS: qRT-PCR and Chromogenic in Situ Hybridization (CISH) was conducted to assess the expression of miR-608 in paired BCa tissues and adjacent non-tumor bladder urothelial tissues. Bisulfite sequencing PCR was used for DNA methylation analysis. CCK-8, colony formation and flow cytometry assays were performed, and a xenograft model was studied. Immunohistochemistry staining was performed with peroxidase and DAB. The target of miR-608 was validated with a dual-luciferase reporter assay, quantitative RT-PCR, and Western blotting. RESULTS: miR-608 is frequently down-regulated in human BCa tissues. The methylation status of CpG islands is involved in the regulation of miR-608 expression. Overexpression of miR-608 inhibits the proliferation and tumorigenesis of BCa cells in vitro and in vivo. Additionally, up-regulation of miR-608 in BCa cells induces G1-phase arrest through AKT/FOXO3a signaling. In contrast, down-regulation of miR-608 promotes proliferation and cell cycle progression in BCa cells. Moreover, the expression of FLOT1 was directly inhibited by miR-608, the down-regulation of FLOT1 induced by siFLOT1 could be significantly reversed by miR-608 inhibitor. Similarly, the up-regulation of FLOT1 by FLOT1 overexpression plasmid (pFLOT1) could also reverse the suppressed cell proliferation caused by miR-608. CONCLUSIONS: miR-608 is a potential tumor suppressor in BCa, and the restoration of miR-608 might be a promising therapeutic option for BCa.

When to perform bone scintigraphy in patients with newly diagnosed prostate cancer? a retrospective study.

BACKGROUND: To determine when a bone scintigraphy investigation is appropriate in patients with newly diagnosed prostate cancer (PCa). METHODS: We retrospectively reviewed 703 newly diagnosed PCa patients who were referred for bone scintigraphy. The association between age, prostate specific antigen (PSA), Gleason score (GS) and bone scintigraphy result were investigated by series of crude or stratified analysis. RESULTS: Overall, 15.08% (106/703) patients had bone metastases. PSA and GS between positive bone scan group and negative bone scan group were significantly different, while age was not. The incidence of bone metastasis in patient with PSA < 20 ng/ml or GS < 8 was less than 10%, but increased dramatically with rising PSA and upgrading GS. In multivariate analysis, PSA ≥ 20 ng/ml (OR = 5.10, 95%CI (2.12-12.27)) and GS ≥ 8 (OR = 3.61, 95%CI (1.55-8.41)) were independently predictive of positive bone scan. CONCLUSIONS: Patients with PSA ≥ 20 ng/ml or GS ≥ 8 were in higher risk of bone metastasis, bone scintigraphy was recommended. But a bone scintigraphy is of limited value in PCa patients with PSA ≤ 20 ng/ml and GS ≤ 7.