BACKGROUND:Prostate cancer (PCa) initially shows satisfactory response to therapies targeting the androgen receptor (AR). However, progression to a castration-resistant stage indicates poor prognosis in PCa patients. AR signalling still plays a central role in most castration-resistant prostate cancers (CRPC). Therefore, unveiling the mechanisms of AR reactivation under androgen-deprived conditions is imperative to discover novel therapeutic targets for CRPC. METHODS:Using an integrative analysis of the transcriptomics of three independent PCa cohorts and a published landscape of AR-regulated long non-coding RNA (lncRNA), lncRNA LINC01126 was selected as a candidate gene that could drive CRPC progression for further study. Quantitative reverse transcription polymerase chain reaction, in situ hybridisation (ISH) and fluorescent ISH were performed to detect LINC01126 in PCa tissues and cells. The functional role and mechanism of LINC01126 were further investigated using in vitro and in vivo gain and loss of function assays. RESULTS:LINC01126, identified as an AR-repressed lncRNA, was significantly upregulated after AR-targeted therapies. In addition, we found that LINC01126 was upregulated in CRPC and was associated with poor prognosis. We also proved that LINC01126 stabilised AR protein and enhanced AR nuclear translocation and transactivation by promoting the transition from O-GlcNAcylation at threonine 80 to phosphorylation at serine 81 (S81) within the AR protein. Mechanism analysis revealed that LINC01126 facilitates the interaction of CDK9 with AR and impedes the binding of O-linked N-acetylglucosamine (O-GlcNAc) transferase to AR. Consequently, LINC01126 expression was sufficient to activate AR signalling without androgen. LINC01126 overexpression increased, whereas LINC01126 knockdown decreased castration resistance traits in PCa cells in vitro and in vivo. Furthermore, our data showed that LINC01126-targeting antisense oligonucleotides (ASO) substantially inhibited CRPC cells in vitro. CONCLUSIONS:Our research expands the functions of AR-regulated lncRNA in sustaining androgen-independent AR activity and promoting CRPC progression and reveals that LINC01126 may be a new therapeutic target for PCa.

Urothelial carcinoma (UC) is a common malignancy that remains a clinical challenge: Non-muscle-invasive urothelial carcinoma (NMIUC) has a high rate of recurrence and risk of progression, while muscle-invasive urothelial carcinoma (MIUC) has a high mortality. Although some new treatments, such as immunotherapies, have shown potential effects on some patients, most cases of advanced UC remain incurable. While treatments based on epigenetic mechanisms, whether combined with traditional platinum-based chemotherapy or emerging immunotherapy, show therapeutic advantages. With the advancement of sequencing and bioinformatics, the study of epigenomics, containing DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA, is increasingly linked with the occurrence and progression of UC. Since the epigenetics of UC is a constantly developing field of medicine, this review aims to summarize the latest research on epigenetic regulation of UC, generalize the mechanism of epigenetics in UC, and reveal the potential epigenetic therapies in the clinical setting, in order to provide some new clues on the discovery of new drugs based on the epigenetics.

No AccessJournal of UrologyAdult Urology5 Oct 2023Reply By Authorsis a reply to letterEditorial CommentEditorial Comment Wei Tang, Yongxiang Tang, Lin Qi, Ye Zhang, Guyu Tang, Xiaomei Gao, Shuo Hu, and Yi Cai Wei TangWei Tang https://orcid.org/0000-0001-7411-3268 Department of Urology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China Equal study contribution. More articles by this author , Yongxiang TangYongxiang Tang Department of PET Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China Equal study contribution. More articles by this author , Lin QiLin Qi Department of Urology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China More articles by this author , Ye ZhangYe Zhang https://orcid.org/0000-0001-6692-2452 Department of Oncology, NHC Key Laboratory of Cancer Proteomics, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China More articles by this author , Guyu TangGuyu Tang https://orcid.org/0000-0003-0976-3939 Department of Urology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China More articles by this author , Xiaomei GaoXiaomei Gao https://orcid.org/0000-0002-9247-5825 Department of Pathology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China More articles by this author , Shuo HuShuo Hu Department of PET Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China More articles by this author , and Yi CaiYi Cai †Correspondence: Department of Urology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha City, 410008, Hunan Province , PR China telephone: E-mail Address: [email protected] https://orcid.org/0000-0001-7773-2064 Department of Urology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003680.03AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookLinked InTwitterEmail "Reply By Authors." The Journal of Urology, Publish Ahead of Print, pp. REFERENCES 1. Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021; 19(4):439-457. Crossref, Medline, Google Scholar 2. Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022; 20(6):691-722. Crossref, Medline, Google Scholar 3. Benign prostatic hyperplasia−related false-positive of prostate-specific membrane antigen−positron emission tomography in the diagnosis of prostate cancer: the Achilles’ heel of biopsy-free radical prostatectomy?J Urol. 2023; 210(6):000-000. Google Scholar Support: This research was supported by the key Research and Development program of Hunan Province (2021SK2014), the Science and Technology Innovation Team Talent Project of Hunan Province (2021 RC4056), the National Natural Science Foundation of China (82272907, 81974397, 81572524, 91859207, 81771873), the National Natural Science Foundation of Hunan Province (2020JJ5882, 2020JJ5949), and the clinical research foundation of the National Clinical Research Center for Geriatric Diseases (XIANGYA) (2020LNJJ01). Conflict of Interest Disclosures: The Authors declare that they have no conflict of interest. Ethics Statement: The study protocol was approved by the Ethics Committee of Xiangya Hospital (IRB No. 202110113). All patients provided written informed consent to participate in the study. Author Contributions: Wei Tang analyzed the data, interpreted the results, prepared the figures and tables, and wrote the manuscript. Xiaomei Gao analyzed the histopathologic and immunohistochemical data. Yongxiang Tang and Shuo Hu analyzed the data of PSMA-PET. Ye Zhang performed the IHC staining assay and analyzed the results. Guyu Tang prepared the figures and tables. Yi Cai and Lin Qi designed the study and revised the manuscript for important intellectual content. All authors approved the final version of the manuscript. Data Availability: The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology5 Oct 2023Editorial CommentJournal of Urology5 Oct 2023Editorial Comment Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.Metrics Author Information Wei Tang Department of Urology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China Equal study contribution. More articles by this author Yongxiang Tang Department of PET Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China Equal study contribution. More articles by this author Lin Qi Department of Urology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China More articles by this author Ye Zhang Department of Oncology, NHC Key Laboratory of Cancer Proteomics, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China More articles by this author Guyu Tang Department of Urology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China More articles by this author Xiaomei Gao Department of Pathology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China More articles by this author Shuo Hu Department of PET Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China More articles by this author Yi Cai Department of Urology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China †Correspondence: Department of Urology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha City, 410008, Hunan Province , PR China telephone: E-mail Address: [email protected] More articles by this author Expand All Support: This research was supported by the key Research and Development program of Hunan Province (2021SK2014), the Science and Technology Innovation Team Talent Project of Hunan Province (2021 RC4056), the National Natural Science Foundation of China (82272907, 81974397, 81572524, 91859207, 81771873), the National Natural Science Foundation of Hunan Province (2020JJ5882, 2020JJ5949), and the clinical research foundation of the National Clinical Research Center for Geriatric Diseases (XIANGYA) (2020LNJJ01). Conflict of Interest Disclosures: The Authors declare that they have no conflict of interest. Ethics Statement: The study protocol was approved by the Ethics Committee of Xiangya Hospital (IRB No. 202110113). All patients provided written informed consent to participate in the study. Author Contributions: Wei Tang analyzed the data, interpreted the results, prepared the figures and tables, and wrote the manuscript. Xiaomei Gao analyzed the histopathologic and immunohistochemical data. Yongxiang Tang and Shuo Hu analyzed the data of PSMA-PET. Ye Zhang performed the IHC staining assay and analyzed the results. Guyu Tang prepared the figures and tables. Yi Cai and Lin Qi designed the study and revised the manuscript for important intellectual content. All authors approved the final version of the manuscript. Data Availability: The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. 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319 Background: Radical prostatectomy (RP) is the primary treatment for localized clinically significant prostate cancer (csPCa). However, its application is generally based on prior pathological diagnosis. 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) has recently been found to have high diagnostic efficacy and is considered promising in biopsy-free RP. Notably, inadequate specific or positive predictive value of imaging diagnosis strategy could become the Achilles’ Heel of biopsy-free RP. For 68Ga-PSMA PET/CT, the expression of PSMA in benign prostatic hyperplasia (BPH) tissue and its related positive reaction, which can reduce the specificity of diagnosis, are important concerns affecting the imaging diagnosis of PCa as well as the feasibility of biopsy-free RP. Currently, no study has explored the BPH-related false positive rate of 68Ga-PSMA PET/CT in the detection of PCa. Furthermore, the influence of maximum standardized uptake value (SUVmax) on biopsy-free RP is also poorly characterized. Methods: To investigate BPH-related false positive rate of 68Ga-PSMA PET/CT in detecting PCa and the influence of SUVmax on biopsy-free RP, a retrospective descriptive observational study was conducted. Patients who received 68Ga-PSMA PET/CT because of clinical suspicion of PCa based on elevated prostate-specific antigen (> 4ng/ml) or abnormal digital rectal examination and subsequently were confirmed to be BPH or PCa by systematic biopsy or targeted biopsy (TB) were included. The receiver operating characteristic curve was generated for SUVmax values, from which the area under the curve (AUC) and the Youden index was calculated. Sensitivity and specificity were calculated based on the cutoffs. Results: A total of 89 BPH and 94 PCa patients who met the inclusion criteria were included. 27 of the 89 BPH cases were considered 68Ga-PSMA PET/CT positive, all dominant lesions were confirmed to be BPH tissue through TB, and thus, were regarded as BPH-related false positive. The BPH-related false positive rate of 68Ga-PSMA PET/CT in the detection of PCa was 30.3%. SUVmax could effectively distinguish BPH and grade group (GG) one patients with an AUC of 0.8562 and could potentially benefit biopsy-free RP by avoid BPH-related misdiagnosis and GG one-related overtreatment. The optimal SUVmax cutoff value was 9.750 with a sensitivity of 64.71% and a specificity of 97.22%. Given the pivotal role of specificity in biopsy-free RP, we investigated the optimal SUVmax cutoff under when the specificity was 100%. The result was 14.60, with a sensitivity of 41.18% and a specificity of 100%. Conclusions: Our results revealed, for the first time, the BPH-related false positive rate of 68Ga-PSMA PET/CT in the primary diagnosis of PCa. Using SUVmax values in biopsy-free RP can effectively exclude both BPH and GG one patients.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent urological carcinomas with a low overall 5-year survival rate, and its prognosis remains dismal. circular RNA (circRNA) has been discovered to be important regulators in ccRCC. However, the specific regulatory mechanisms of circRNA and its impact on phenotypes require further in-depth research. Methods: circRNA microarray sequencing analysis was used in this study to explore the expression pattern of circRNA in ccRCC. circWSB1 was discovered, and we evaluated its derivation, potential diagnostic efficacy, and prognostic significance in ccRCC tissues using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and sanger sequencing. Fluorescence in situ hybridization analysis (FISH), RNA immunoprecipitation, and dual-luciferase reporter gene assays were used to investigate the subcellular localization and regulation mechanism of circWSB1. In vivo and in vitro loss-of-function and gain-of-function experiments were used to determine the biological functions of circWSB1. Results: Through RNA sequencing of five pairs of tumor and adjacent tissues, we discovered that circWSB1 is highly expressed in ccRCC. We identified that circWSB1 interacts with miR-182-5p and upregulates the expression of its host gene, WSB1. Through models in vivo and in vitro, we found circWSB1 increases WSB1 expression via the circWSB1/miR-182-5p/WSB1 axis, which promotes ccRCC cell proliferation and migration. The high expression of circWSB1 and WSB1 is correlated with poorer clinical prognosis and pathological grading. Conclusions: circWSB1 diminishes the inhibitory impact of miR-182-5p on WSB1, and increases WSB1 expression, thereafter promotes ccRCC development. Our findings provide a promising predictive biomarker and therapeutic target for ccRCC. Citation Format: Guyu Tang, Jing Liu, Xiaomei Gao, Wei Tang, Jiaxian Chen, Menghai Wu, Ye Zhang, Yi Cai, Lin Qi. circWSB1 promotes tumor progression in ccRCC via circWSB1/miR-182-5p/WSB1 axis [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C088.

You have accessJournal of UrologyCME1 Apr 2023PD38-02 BPH-RELATED FALSE POSITIVE OF 68GA-PSMA PET/CT IN THE DIAGNOSIS OF PROSTATE CANCER: THE ACHILLES' HEEL OF BIOPSY-FREE RADICAL PROSTATECTOMY? Wei Tang, Yongxiang Tang, Lin Qi, Ye Zhang, Guyu Tang, Xiaomei Gao, Shuo Hu, and Yi Cai Wei TangWei Tang More articles by this author , Yongxiang TangYongxiang Tang More articles by this author , Lin QiLin Qi More articles by this author , Ye ZhangYe Zhang More articles by this author , Guyu TangGuyu Tang More articles by this author , Xiaomei GaoXiaomei Gao More articles by this author , Shuo HuShuo Hu More articles by this author , and Yi CaiYi Cai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003336.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical prostatectomy (RP) is the primary treatment for localized clinically significant prostate cancer (csPCa). However, its application is generally based on prior pathological diagnosis. 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) is considered promising in biopsy-free RP. Notably, inadequate specific or positive predictive value of imaging diagnosis strategy could become the Achilles’ Heel of biopsy-free RP. For 68Ga-PSMA PET/CT, the expression of PSMA in benign prostatic hyperplasia (BPH) tissue and its related positive reaction, which can reduce the specificity of diagnosis, are important concerns affecting the imaging diagnosis of PCa as well as the feasibility of biopsy-free RP. No study has explored the BPH-related false positive of 68Ga-PSMA PET/CT in the detection of PCa. Furthermore, the influence of maximum standardized uptake value (SUVmax) on biopsy-free RP is also poorly characterized. METHODS: A retrospective descriptive observational study was conducted. Patients who received 68Ga-PSMA PET/CT because of clinical suspicion of PCa based on elevated prostate-specific antigen ( >4 ng/ml) or abnormal digital rectal examination and subsequently were confirmed to be BPH or PCa by systematic biopsy or targeted biopsy (TB) were included. The receiver operating characteristic curve was generated for SUVmax values, from which the area under the curve (AUC) and the Youden index was calculated. Sensitivity and specificity were calculated based on the cutoffs. RESULTS: 89 BPH and 94 PCa patients were included. 27 of the 89 BPH cases were considered 68Ga-PSMA PET/CT positive, all dominant lesions were confirmed to be BPH tissue through TB, and thus, were regarded as BPH-related false positive. The rate was 30.3%. SUVmax could effectively distinguish BPH and grade group (GG) one patients with an AUC of 0.8562 and could potentially benefit biopsy-free RP by avoid BPH-related misdiagnosis and GG one-related overtreatment. The optimal SUVmax cutoff value was 9.750 with a sensitivity of 64.71% and a specificity of 97.22%. Given the pivotal role of specificity in biopsy-free RP, we investigated the optimal SUVmax cutoff under when the specificity was 100%. The result was 14.60, with a sensitivity of 41.18% and a specificity of 100%. CONCLUSIONS: Our results revealed, for the first time, the BPH-related false positive rate of 68Ga-PSMA PET/CT in the primary diagnosis of PCa. Using SUVmax values in biopsy-free RP can effectively exclude both BPH and GG one patients. Source of Funding: This research was supported by the key Research and Development program of Hunan Province (2021SK2014), the Science and Technology Innovation Team Talent Project of Hunan Province (2021 RC4056), the National Natural Science Foundation of China (82272907, 81974397, 81572524, 91859207, 81771873), the National Natural Science Foundation of Hunan Province (2020JJ5882) and the clinical research foundation of the National Clinical Research Center for Geriatric Diseases (XIANGYA) (2020LNJJ01) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e993 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wei Tang More articles by this author Yongxiang Tang More articles by this author Lin Qi More articles by this author Ye Zhang More articles by this author Guyu Tang More articles by this author Xiaomei Gao More articles by this author Shuo Hu More articles by this author Yi Cai More articles by this author Expand All Advertisement PDF downloadLoading ...

Background: As a transcription factor, Zic family member 2 (ZIC2) has been involved in more and more studies of tumorigenesis, which has been proved by our research team to be an effective prognostic marker for Pan-cancer. However, the prognosis, tumor promoting effect and regulatory mechanism of ZIC2 in clear cell renal cell carcinoma (ccRCC) are still unknown.Methods: The potential clinical significance of ZIC2 was evaluated by bioinformatics analysis using data from TCGA, GEO, and ArrayExpress data sets. WB and IHC were used to detect ZIC2 expression in tumors and adjacent tissues. CCK-8, EdU, colony formation, cell cycle, wound healing, transwell, subcutaneous xenograft, and lung metastasis models were used to detect the biological function of ZIC2. The regulatory mechanism of ZIC2 was confirmed by data of RNA-seq, ATAC-seq, MS-PCR, Chip-PCR, and luciferase reporter experiments.Results: ZIC2 was markedly upregulated and correlated with poor clinicopathological features in ccRCC. Knockdown of ZIC2 resulted in reduced cell proliferation, invasion, migration, induction of G2/M phase arrest, and reduced tumor formation and lung metastasis in nude mice. The opposite was observed after overexpression. Mechanistically, the high expression of ZIC2 is regulated by hypomethylation and high H3K4Me3 in the promoter region, as well as positive transcriptional regulation by FOXM1. And then, ZIC2 transcriptase-positively regulates UBE2C and activates AKT/mTOR signaling pathway to promote tumor malignant progression. Conclusion: This study reveals that FOXM1-ZIC2-UBE2C-mTOR signaling axis promotes the progression of ccRCC, which can be used as a prognostic indicator and potential therapeutic target.

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent urological carcinomas with a low overall 5-year survival rate, and its prognosis remains dismal. circular RNAs (circRNAs) has been discovered to be important regulators in ccRCC. However, the specific regulatory mechanisms of circRNAs and their impact on phenotypes require further in-depth research. circRNA microarray sequencing analysis was used in this study to explore the expression pattern of circRNAs in ccRCC. circWSB1 was discovered, and we evaluated its derivation, potential diagnostic efficacy, and prognostic significance in ccRCC tissues. We discovered that circWSB1 is highly expressed in ccRCC. We identified that circWSB1 interacts with miR-182-5p and upregulates the expression of its host gene, WSB1. Through models in vivo and in vitro models, we found that circWSB1 increases WSB1 expression via the circWSB1/miR-182-5p/WSB1 axis, which promotes ccRCC cell proliferation and migration. The high expression of circWSB1 and WSB1 is correlated with poorer clinical prognosis and pathological grading. circWSB1 diminishes the inhibitory impact of miR-182-5p on WSB1 and increases WSB1 expression, thereafter promoting ccRCC development. Our findings provide a promising predictive biomarker and therapeutic target for ccRCC.

Castration-resistant prostate cancer (CRPC) is a therapy-resistant and lethal form of prostate cancer as well as a therapeutic challenge. Prostate-specific membrane antigen (PSMA) has been proved as a promising molecular target for optimizing the theranostics for CRPC patients. When combined with PSMA radiotracers, novel molecular imaging techniques such as positron emission tomography (PET) can provide more accurate and expedient identification of metastases when compared with conventional imaging techniques. Based on the PSMA-based PET scans, the accurate visualization of local and disseminative lesions may help in metastasis-directed therapy. Moreover, the combination of 68Ga-labeled PSMA-based PET imaging and radiotherapy using PSMA radioligand therapy (RLT) becomes a novel treatment option for CRPC patients. The existing studies have demonstrated this therapeutic strategy as an effective and well-tolerated therapy among CRPC patients. PSMA-based PET imaging can accurately detect CRPC lesions and describe their molecular features with quantitative parameters, which can be used to select the best choice of treatments, monitor the response, and predict the outcome of RLT. This review discussed the current and potential role of PSMA‐based imaging and RLT in the diagnosis, treatment, and prediction of prognosis of CRPC.

Abstract Background To investigate the prognostic factors affecting long-term survival in locally advanced cervical cancer (LACC) patients treated with concurrent chemoradiotherapy (CCRT). Methods We retrospectively analyzed 192 naive LACC (stage IIB–IVA) patients who underwent intensity-modulated radiotherapy (IMRT) with concurrent platinum-based chemotherapy in Xiangya Hospital from January 2014 to June 2017. The clinicopathological factors of all patients were collected. To explore the relationship between factors and prognosis, survival rates were estimated by the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards models were used to evaluate the effect of various factors on overall survival (OS) and progression-free survival (PFS). The nomogram and calibration curves were generated on the basis of survival analysis. Results The median follow-up time was 39.5 months. There-year rates of OS and PFS were 89.1% and 82.8%. LACC patients with non-squamous cell carcinoma [NSCC, including adenocarcinoma or adenosquamous carcinoma (AC/ASC)], advanced stage (IIIA-IVA), initially positive lymph node (pelvic or para-aortic lymph node, PLN/PALN), and a lower pretreatment hemoglobin (HGB) level (< 126 g/L) had lower survival rates. In univariate analysis, patients with NSCC, advanced stage, PLN or PALN metastasis had worse OS. Patients with NSCC, advanced stage, PLN or PALN metastasis, and a lower pretreatment HGB level had worse PFS. In multivariate analysis, NSCC and PALN metastasis were independent prognostic parameters of OS. NSCC, PALN metastasis and a lower pretreatment HGB level were independent prognostic parameters of PFS. Conclusions NSCC and PALN metastasis were poor prognostic factors of OS and PFS, a lower pretreatment HGB level was an independent prognostic factor of PFS in LACC patients treated with CCRT.

The most prevalent pathological subtype of bladder and upper urinary tract malignancy is urothelial carcinoma (UC). Traditional therapies mainly include surgical resection, chemotherapy and radiotherapy. Checkpoint inhibitors, which are monoclonal antibodies developed to specifically target immune checkpoint molecules, have recently emerged as potential treatment options for UC patients, especially those targeting the programmed cell death protein 1 (PD-1) and its ligand (PD-L1). However, anti-PD-1/PD-L1 therapy does not work for a considerable number of UC patients. Current antitumour immunotherapy research hotspots include seeking biomarkers that might predict therapeutic effects and exploring novel immune checkpoint molecules crucial for the antitumour immune response. Hence, we will recapitulate the latest preclinical and clinical trials of 5 PD-1/PD-L1 inhibitors, 1 cytotoxic T-lymphocyte-associated protein 4 inhibitor and combination therapies for UC treatment, including combined immunotherapy and immunotherapy with chemotherapy or radiotherapy. We will also summarize other potential immune checkpoint molecules found in ongoing UC studies. Moreover, we will highlight the role of biomarkers linked with the oncological efficacy of anti-PD-1/PD-L1 immunotherapy and address the mechanisms of immunotherapy drug resistance in UC, with the hope of providing more systematic guidance for its application and development.

Ferroptosis induced by lipid peroxidation is closely related to cancer biology. Prostate cancer (PCa) is not only a malignant tumor but also a lipid metabolic disease. Previous studies have identified ferroptosis as an important pathophysiological pathway in PCa development and treatment, but its role in the prognosis of PCa is less well known. In this study, we constructed a nine-ferroptosis-related gene risk model that demonstrated strong prognostic and therapeutic predictive power. The higher risk score calculated by the model was significantly associated with a higher ferroptosis potential index, higher Ki67 expression, higher immune infiltration, higher probability of biochemical recurrence, worse clinicopathological characteristics, and worse response to chemotherapy and antiandrogen therapy in PCa. The mechanisms identified by the gene set enrichment analysis suggested that this signature can accurately distinguish high- and low-risk populations, which is possibly closely related to variations in steroid hormone secretion, regulation of endocrine processes, positive regulation of humoral immune response, and androgen response. Results of this study were confirmed in two independent PCa cohorts, namely, The Cancer Genome Atlas cohort and the MSK-IMPACT Clinical Sequencing Cohort, which contributed to the body of scientific evidence for the prediction of biochemical recurrence in patients with PCa. In addition, as the main components of this signature, the effects of the AIFM2 and NFS1 genes on ferroptosis were evaluated and verified by in vivo and in vitro experiments, respectively. The above findings provided new insights and presented potential clinical applications of ferroptosis in PCa.

Purpose: To analyze the incidence and risk factors of lower extremity venous thrombosis after urologic surgeries. Methods: A prospective two-center study was conducted from August 2019 to January 2020. 1122 consecutive patients who underwent urologic procedures were enrolled. The study primary end point was the detection of asymptomatic or symptomatic deep vein thrombosis (DVT) of lower extremity within 7 days after the surgeries. Univariate and LASSO-logistics regression analysis were performed. Results: We excluded 111 patients who met exclusion criteria. Totally, 56 (5.54%) out of 1011 patients had developed DVT. In the univariate analysis, Barthel Index ≤40, D-dimer levels ≥0.5mg/L and age≥ 60 yrs (p <0.001) were the most significant risk factors. The LASSO-logistics regression model identified 9 factors including age, history of DVT, lymph nodes dissection, perioperative steroid use, Caprini Score, Barthel Index, D-dimer levels, cystectomy and prostatectomy. Conclusion: Our study used the LASSO-logistic regression model to provide reliable data on risk factors of DVT after comprehensive urologic surgeries. It might facilitate individualized anticoagulant management of patients undergoing urologic procedures. Trial registration: ChiCTR1900024784

Bladder cancer (BC) is one of the most commonly diagnosed cancers globally. Recently, circular RNAs (circRNAs) have been revealed to participate in BC progression with diverse mechanisms. However, mechanisms of circ_100984 in BC have not been determined. Here, we found that circ_100984 and YBX-1 were high presented, while miR-432-3p was low presented in BC. Silencing of circ_100984 and YBX-1 repressed BC tumor growth, migration, and invasion in vitro and in vivo. Mechanistically, we revealed that circ_100984 served as a competing endogenous RNA that sponged miR-432-3p to indirectly regulate YBX-1 and epithelial-mesenchymal transition (EMT)-related molecules. Moreover, we confirmed that YBX-1 or c-Jun acted as a transcription regulatory factor for β-catenin or YBX-1, respectively, in BC cells. Knockdown of YBX-1 inhibited the expression of β-catenin and c-Jun, whereas downregulated c-Jun inversely repressed the expression of YBX-1 and β-catenin. Our results suggested that circ_100984-miR-432-3p axis regulated c-Jun/YBX-1/β-catenin feedback loop promotes BC progression, providing a potential therapeutic axis for BC progression.

Extracranial metastasis from glioblastoma multiforme (GBM) is rare, especially multi-site metastases without intracranial recurrence. However, the metastatic mechanism of GBM remains unknown and there is currently no consensus regarding the best therapeutic regimen. We report the case of a 46-year-old man with primary GBM who developed scalp metastases and subsequent multiple pulmonary metastases. He was treated with the Stupp regimen after surgery for the intracranial tumor. However, a series of soft masses in the scalp were subsequently identified, and new nodules were found in his left eyebrow arch during chemoradiotherapy. Despite salvage chemotherapy and targeted therapy, the patient eventually died of respiratory failure with multiple pulmonary metastases. This case highlights the need for rigorous follow-up, including brain magnetic resonance imaging, in patients with GBM. The occurrence of extra-central nervous system symptoms indicates the possibility of metastasis, and the relevant examinations should be conducted promptly. Positive therapies may help to relieve symptoms and prolong survival in patients with metastatic GBM.

Purpose To explore the possibility of intraoperative transrectal ultrasound (TRUS)-based dose verification in transperineal brachytherapy (BT) with iodine-125 (125I) seeds for prostate cancer. Material and methods Fifteen patients with prostate cancer were treated using BT with 125I seeds. Post-implant TRUS and computed tomography (CT) images were imported into treatment planning system (TPS) for dosimetry. Dosimetry parameters, including minimum dose received by 90% of the volume (D90), percentage of the volume receiving 100% of prescribed dose (V100), and percentage of the volume receiving 200% of prescribed dose (V200) were calculated based on TRUS and CT images, separately. The D90 value of TRUS-based dosimetry was transformed to its expected value. Comparisons of the dosimetric parameters between post-operative verification and preoperative plans were made by paired t-test. One-way ANOVA model was used to assess the differences in preoperative plans. Agreements were evaluated between the preoperative planning and post-operative actual dose parameters using Bland-Altman analysis. Results In total, 825 of 125I seeds were implanted successfully in 15 patients. In TRUS-based dosimetry, 674 seeds (81%) were identified clearly in TRUS-based images, and the expected value of D90 parameter showed no significant differences compared with the preoperative planning and CT post-operation results (p > 0.05). In CT-based dosimetry, 810 seeds (98%) were identified clearly in CT-based images, and there was good consistency of D90, V100, and V200 values (p > 0.05). Post-implant CT-based dosimetry indicated that 125I seed implantation had fulfilled the expected plan. Conclusions Intraoperative TRUS can be used for dosimetric verification of BT for prostate cancer.