From Cognitive MR-Targeted Fusion Prostate Biopsy to Radical Prostatectomy: Incidence and Predictors of Gleason Grade Group Upgrading in a Chinese Cohort.

Purpose: To access the incidence and predictors of Gleason grade group upgrading from cognitive MR-targeted fusion prostate biopsy to radical prostatectomy in a Chinese cohort. Materials and Methods: We included 199 patients in our institution between January 2016 and June 2021. Multivariable logistic regression model and nomograms were utilized to analyze the collected data. Results: The concordance rate of biopsy Gleason grade group and radical prostatectomy was 50.3% (100 in 199). Upgrading occurred in 80 (40.2%) patients and 37 (68.5%) patients have an upgrading Gleason grade group when the biopsy Gleason grade group was 1. Multivariable logistic regression models were established to analyze the incidence and predictors of Gleason grade group upgrading from cognitive MR-targeted fusion prostate biopsy to radical prostatectomy. Biopsy Gleason grade group, prostate volume, and patient year were confirmed to be individual predictors of upgrading. Based on the logistic regression models, nomograms for predicting probability of prostate Gleason grade group upgrading were generated. Conclusions: We established a logistic regression model to predict the accuracy of prostate biopsy GG and provide the probability of upgrading. Clinicians should be more cautious when deciding the treatment strategy especially for prostate cancer biopsy GG1 patients. Future studies should expand the sample size and include more variables to improve the accuracy of predicting upgrading and prostate cancer early screening program is urgently needed in our city in China.

Roles and mechanisms of the m6A reader YTHDC1 in biological processes and diseases.

N6-methyladenosine (m6A) is a key area in Epigenetics and has been increasingly focused these years. In the m6A process, readers recognize the m6A modification on mRNAs or noncoding RNAs and mediate different downstream events. Emerging studies have shown that YTHDC1, an important m6A reader, plays a key role in many biological functions and disease progression, especially cancers. Here we summarized the current mechanisms of YTHDC1 in biological functions and diseases and offered guidance for future researches to provide potential strategy for clinical diagnose and therapy.

LncRNA FGF14-AS2 represses growth of prostate carcinoma cells via modulating miR-96-5p/AJAP1 axis.

OBJECTIVE: This investigation devoted to lncRNA FGF14 antisense RNA 2 (FGF14-AS2) in prostate carcinoma progression. METHODS: The levels of lncRNA FGF14-AS2, miR-96-5p, and Adherens junction-associated protein-1 (AJAP1) in prostate carcinoma were tested by Western blot and qRT-PCR. How these two genes interacted was confirmed by RNA immunoprecipitation and dualluciferase gene methods. The effect of FGF14-AS2/miR-96-5p/AJAP1 axis in prostate carcinoma progression was determined by MTT, Transwell, and nude mice tumor model. RESULTS: FGF14-AS2 was a downregulated lncRNA in prostate carcinoma tissue and cells. FGF14-AS2 could restrain miR-96-5p expression while miR-96-5p hampered AJAP1. FGF14-AS2 could effectively decrease the biological behaviors of prostate carcinoma cells, while knock-down of FGF14-AS2 triggered opposite results. Moreover, miR-96-5p mimic presented a cancer promoter role in prostate carcinoma cells. AJAP1 expression level could affect levels of proteins related to epithelial-mesenchymal transition. In vivo experiment suggested that overexpressing FGF14-AS2 could reverse the promotion of silenced AJAP1 on prostate carcinoma cell metastasis, thus to inhibit tumor growth. CONCLUSION: lncRNA FGF14-AS2 was a downregulated lncRNA in prostate carcinoma and influenced cell proliferation and metastasis. The influence relied on modulating miR-96-5p and its target gene AJAP1.

Metabolomic profiling identifies novel biomarkers and mechanisms in human bladder cancer treated with submucosal injection of gemcitabine.

Bladder cancer (BCa) is a common urinary tract malignancy with frequent recurrences after initial resection. Submucosal injection of gemcitabine prior to transurethral resection of bladder tumor (TURBT) may prevent recurrence of urothelial cancer. However, the underlying mechanism remains unknown. In the present study, ultra­performance liquid chromatography Q­Exactive mass spectrometry was used to profile tissue metabolites from 12 BCa patients. The 48 samples included pre­ and post­gemcitabine treatment BCa tissues, as well as adjacent normal tissues. Principal component analysis (PCA) revealed that the metabolic profiles of pre­gemcitabine BCa tissues differed significantly from those of pre­gemcitabine normal tissues. A total of 34 significantly altered metabolites were further analyzed. Pathway analysis using MetaboAnalyst identified three metabolic pathways closely associated with BCa, including glutathione, purine and thiamine metabolism, while glutathione metabolism was also identified by the enrichment analysis using MetaboAnalyst. In search of the possible targets of gemcitabine, metabolite profiles were compared between the pre­gemcitabine normal and post­gemcitabine BCa tissues. Among the 34 metabolites associated with BCa, the levels of bilirubin and retinal recovered in BCa tissues treated with gemcitabine. When comparing normal bladder tissues with and without gemcitabine treatment, among the 34 metabolites associated with BCa, it was observed that histamine change may be associated with the prevention of relapse, whereas thiamine change may be involved in possible side effects. Therefore, by employing a hypothesis­free tissue­based metabolomics study, the present study investigated the metabolic signatures of BCa and found that bilirubin and retinal may be involved in the mechanism underlying the biomolecular action of submucosal injection of gemcitabine in urothelial BCa.

miR-143 inhibits bladder cancer cell proliferation and enhances their sensitivity to gemcitabine by repressing IGF-1R signaling.

microRNAs (miRNAs) are a class of small RNAs that regulate gene expression. It has been demonstrated that aberrant miRNA expression is associated with cancer development and carcinogenesis. Altered miRNA expression has been suggested to occur in bladder cancer. In other cancer systems, studies have indicated that miR-143, as a tumor suppressor gene, plays essential roles in cancer progression. However, its role in bladder cancer has yet to be elucidated. In the present study, we observed that miR-143 expression was downregulated in human bladder cancer tissues and cells, and that its levels were negatively correlated with bladder cancer clinical stages. We further demonstrated that insulin-like growth factor-1 receptor (IGF-1R) is a functional target of miR-143. Their expression levels were inversely correlated in bladder cancer samples. Overexpression of miR-143 inhibited cell proliferation and promoted chemosensitivity of bladder cancer 5637 cells to gemcitabine. Consistently, small interfering RNA-mediated knockdown of IGF-1R phenocopied miR-143 overexpression. Notably, the expression of IGF-1R is a predictor of patient prognosis. Collectively, our findings indicate that miR-143 is a valuable biomarker for bladder cancer. The miR-143/IGF-1R axis is associated with bladder cancer drug resistance and patient survival.