Objective: This study aims to investigate the role of BMAL1 in promoting angiogenesis in cerebral glioma among athletes by regulating vascular endothelial growth factor (VEGF) and angiopoietin-2 (ANG2). Methods: Human brain tumor cells, representative of gliomas often observed in athletes, were categorized into three groups: blank, control, and BMAL1-treated research group. Cell growth and apoptosis were analyzed using the MTT assay and flow cytometry, respectively. VEGF and ANG2 expressions, along with microvessel density (MVD), were assessed via immunohistochemistry. The Spearman rank test evaluated the correlation between VEGF and ANG2 levels. Further, groups A, B, and C (representing different pathological grades of human glioma tissues) and BMAL1-treated groups (D, E, and F) were compared to analyze BMAL1's role in modulating VEGF and ANG2. Results: The control group showed significantly lower cell survival and higher apoptosis rates compared to the blank group (P<0.05). Higher glioma grades correlated positively with increased apoptosis rates (P<0.05). VEGF, ANG2, and MVD expressions were significantly higher in the control group than in the blank group (P<0.05), with notable differences observed between the study and control groups (P<0.05). A positive correlation was found between glioma grade, MVD count, and the expressions of VEGF and ANG2 (P<0.05). Groups D, E, and F demonstrated significant differences in VEGF and ANG2 expressions, with group F exhibiting the highest levels (P<0.05), indicating BMAL1's regulatory effect on these angiogenic factors. Conclusion: The study confirms that BMAL1 regulates VEGF and ANG2 expression, promoting angiogenesis in cerebral glioma, a condition relevant to athletes due to their unique physiological stresses. This highlights the potential of targeting BMAL1 in developing therapeutic strategies for glioma angiogenesis in athletic populations, providing a novel approach to manage this challenging aspect of cerebral glioma treatment.

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III (PD59)1 Apr 2020PD59-04 PROX1 AS A NEW DRIVER IN THE REGULATION OF NEUROENDOCRINE DIFFERENTIATION AND CELLULAR PLASTICITY IN PROSTATE CANCER Kaijie Wu*, Ke Hui, Shiqi Wu, and Dalin He Kaijie Wu*Kaijie Wu* More articles by this author , Ke HuiKe Hui More articles by this author , Shiqi WuShiqi Wu More articles by this author , and Dalin HeDalin He More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000969.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: With the application of the next-generation AR pathway inhibitor (ARPIs), such as enzalutamide, patients with metastatic castration resistant prostate cancer (mCRPC) acquire a significant survival benefit. However, a proportion of patients undergo neuroendocrine differentiation (NED) and progress to neuroendocrine prostate cancer (NEPC), and finally show resistance to ARPIs. The underlying mechanisms remain largely unknown. In our previous study, we have demonstrated that Prospero-related homeobox 1 (PROX1) as a critical downstream factor of DAB2IP induced HIF-1alpha protein accumulation and an epithelial-mesenchymal transition (EMT) response, leading to a unique non-skeletal metastasis of PCa. In this study, we will further explore the role of PROX1 in the regulation of NED and cellular plasticity (i.e., EMT and cancer stemness) of PCa. METHODS: Immunohistochemistry (IHC) was performed to evaluate the expression of PROX1 in prostate adenocarcinoma and NEPC tissues. The expression of PROX1 and gene copy number were analyzed in different NEPC models (clinical tissues, patient-derived xenograft models, transgenic mouse models and cell lines) from public databases. In vitro, qPCR and western blot were used to detect the expression of PROX1 in different NEPC cell models (LNCaP with TP53/RB1 loss, PC3, hypoxia-treated 22Rv1, and NCI-H660 cell lines). qPCR was used to evaluate the expression of PROX1 in LNCaP cells which were treated with DHT or charcoal stripped medium, in order to explore the association between PROX1 and AR signalling pathway. The changes of NED and cellular plasticity in C4-2B/MDVR cells with PROX1 knockdown were measured by Boyden chamber assay, qPCR and western blot analysis. In vivo, subcutaneous xenografts in nude mice were used to detect tumorigenicity, and the expression of PROX1, NSE, E-cadherin and CD44 was detected by IHC. RESULTS: PROX1 was uniquely upregulated in NEPC clinical specimens, PDX models, transgenic mouse and cell models due to TP53/RB1 loss, PROX1 gene amplification and hypoxia. Also, activation of AR signalling pathway decreased the expression of PROX1 gene. Furthermore, PROX1 was upregulated in C4-2B/MDVR cell model with NEPC phenotype, and knockdown of PROX1 could reverse NED and cellular plasticity of C4-2B/MDVR cells and restore the sensitivity to enzalutamide treatment in vitro and in vivo. CONCLUSIONS: PROX1 was significantly upregulated in NEPC, which could drive PCa cell NED and cellular plasticity for the development of enzalutamide resistance. Source of Funding: NSFC 81202014 to KW. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1206-e1206 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kaijie Wu* More articles by this author Ke Hui More articles by this author Shiqi Wu More articles by this author Dalin He More articles by this author Expand All Advertisement PDF downloadLoading ...

Background. Recent studies indicate that androgen deprivation therapy (ADT), the main therapeutic approach for metastatic prostate cancer (PCa), accelerates PCa invasion and metastasis. Annexin A1 (ANXA1) is a Ca2+-regulated phospholipid-binding protein that can promote PCa migration and invasion. Aim of the study. The aim of this study is to determine whether ANXA1 is regulated by ADT and participates in PCa progression after ADT, and to explore the possible mechanism of ANXA1-mediated PCa migration. Methods. Expression of ANXA1 and androgen receptor (AR) in PCa cell lines and tissues was detected, and the association between these two proteins were analyzed. Expression of ANXA1 was evaluated after AR knockdown or AR inhibition in PCa cell lines. Cell migration of PCa cell liness after ANXA1 knockdown or overexpression was determined by in vitro migration assay. Transcriptome analysis was used to explore the possible mechanism of ANXA1-mediated PCa migration. Results. ANXA1 expression in PCa cell lines and tissues was reversely associated with AR. In vitro studies revealed an increase in ANXA1 expression after AR knockdown or treatment with AR antagonist. Moreover, functional assays indicated that ANXA1 knock-down in PCa cells significantly inhibited cell migration, while ANXA1 overexpression in PCa cells significantly accelerated cell migration. Transcriptome analysis showed that ANXA1 regulated multiple genes involved in cell junction organization, such as CADM1, LIMCH1 and PPM1F. Conclusions. Our results indicate that ADT might accelerate PCa metastasis via ANXA1 expression and PCa cell migration. (C) 2021 IMSS. Published by Elsevier Inc.

前列腺癌(PCa)是我国常见的男性恶性肿瘤,临床上多用靶向雄激素-雄激素受体(AR)的新型内分泌治疗方法(例如恩杂鲁胺)治疗转移性去势抵抗型前列腺癌(mCRPC),但耐药很快成为新的挑战,使癌细胞不再依赖于AR通路继续生存、生长.其重要机制就是药物诱导部分细胞重组获得神经内分泌癌(NEPC)表型.因此,本文将围绕药物诱导的前列腺癌重塑并转化为NEPC研究的最新进展作一综述,以期为寻找全新的治疗方式提供崭新的思路.

Patients with renal cell carcinoma (RCC) often develop distant metastasis and the specific molecular mechanism remains poorly understood. In our study, we demonstrated that MUC15, a subtype of mucins family, could suppress the progression of RCC by inhibiting PI3K/AKT signaling. Firstly, we observed that MUC15 was notably decreased in RCC compared to normal tissue. Furthermore, we showed that MUC15 could negatively modulate the migration and invasion of RCC in vitro and in vivo. Mechanistically, we found that knocking-down of MUC15 could active the PI3K/AKT signaling by increasing the AKT phosphorylation and subsequently increase the mRNA and protein expression of MMP2 and MMP9. Interruption of the AKT pathway with the specific inhibitor LY294002 could reverse the expression of MMPs. Therefore, our study clarify the novel function of MUC15 in RCC, which may provide a new sight to diagnose and prevent RCC metastasis.

Background: AKR1C3, as a crucial androgenic enzyme, facilitates intratumoral androgen biosynthesis and androgen receptor activation in castration-resistant prostate cancer (PCa). The data has shown that AKR1C3 expression is significantly elevated in clinical metastatic PCa specimens, indicating a potential role of AKR1C3 in PCa metastasis. Methods: C4-2, 22RV1-T, and PC-3 cells with higher AKR1C3 expression were selected and treated with several specific AKR1C3 shRNAs or small molecule inhibitor, and the cell migration and invasion abilities were detected by wound healing assay and Transwell assay. The expression of several epithelial-mesenchymal transition (EMT) markers (i.e., E-cadherin and vimentin) and the related transcription factors (i.e., ZEB1, TWIST1, and SLUG) was examined by Western blot or quantitative PCR assays, and the phosphorylation of AKT or ERK was detected by Western blot. Also, subcutaneous xenografts with 22RV1-T sublines were used to detect in vivo tumor growth, and the expression of E-cadherin, vimentin, and ZEB1 by immunohistochemical staining. The correlation between AKR1C3 and EMT marker expression in clinical specimens was analyzed. Results: AKR1C3 was overexpressed in more aggressive PCa cell lines regardless of the androgen receptor status. Knockdown of AKR1C3 expression or inhibition of AKR1C3 activity could significantly suppress cell migration and invasion abilities in vitro, and increase E-cadherin expression but decrease vimentin expression, in which the phosphorylation of ERK and the EMT-associated transcription factor expression were specifically down-regulated. Also, knockdown of AKR1C3 could suppress PCa tumorigenesis and reverse EMT in vivo. Moreover, there was a significant correlation between AKR1C3 expression and EMT in human PCa specimens from public tissue microarray. Conclusions: AKR1C3 is a novel EMT driver in PCa metastasis through activating ERK signaling. (C) 2018 Elsevier Inc. All rights reserved.

Muscle-invasive or metastatic bladder cancer (BCa) is a life-threatening disease for patients, and tumor angiogenesis is believed to play a critical role in the progression of BCa. However, its underlying mechanism of tumor angiogenesis is still poorly understood. In this study, we discovered that RASAL2, a RAS GTPase activating protein, could inhibit BCa angiogenesis based on our shRNA/siRNA knockdown or ectopic cDNA expression experiments. Mechanistically, RASAL2 downregulation could enhance the phosphorylation of AKT and then subsequently upregulate the expression of ETS1 and VEGFA. Furthermore, there was a negative correlation between RASAL2 and VEGFA or CD31 expression in subcutaneous xenograft and human BCa specimens. Taken together, we provide a new insight into the molecular mechanism of BCa progression, in which RASAL2 can be a new therapeutic target.

Patients with renal cell carcinoma (RCC) often develop resistance to antivascular drugs and eventually succumb to disease. However, the underlying molecular mechanism remains poorly understood. In this study, we demonstrated that RASAL2, a RAS GTPase-activating protein, played a tumor-suppressive role in RCC by targeting tumor angiogenesis. Firstly, we showed that RASAL2 was frequently epigenetically silenced in RCC, and its loss was negatively correlated with overall survival of RCC patients. Furthermore, we discovered that RASAL2 could inhibit RCC angiogenesis in vitro and in vivo. Mechanistically, we identified that RASAL2 could activate GSK3β by reducing Ser9 phosphorylation and subsequently decrease the expression of c-FOS and vascular endothelial growth factor A (VEGFA). Interruption of the p-GSK3β/c-FOS pathway with the specific inhibitor or small interfering RNA could reverse the expression of VEGFA, which may provide a new insight to prevent RCC from resistance to antivascular therapy.

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology III1 Apr 2018MP88-16 THE DOWNREGULATION AND TUMOR SUPPRESSIVE FUNCTION OF RASAL2 IN RENAL CELL CARCINOMA Ke Hui, Kaijie Wu, Jer-Tsong Hsieh, and Dalin He Ke HuiKe Hui More articles by this author , Kaijie WuKaijie Wu More articles by this author , Jer-Tsong HsiehJer-Tsong Hsieh More articles by this author , and Dalin HeDalin He More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2936AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patients with renal cell carcinoma (RCC) often develop resistance to anti-vascular drug and eventually succumb to disease. However, the underlying molecular mechanism of drug resistance remains poorly understood. In this study, we demonstrated that RASAL2, a RAS GTPase activating protein (RASGAP), played suppressive role in in RCC by targeting tumor angiogenesis. METHODS RCC and its paired normal kidney tissues were immunohistochemically stained for RASAL2 expression. Databases downloaded from TCGA or GEO were used to analyze the methylation status of RASAL2 and the correlation between RASAL2 and c-FOS or VEGFA in RCC tissues. In vitro, RASAL2 gain-function in 786-O cells or loss-function in ACHN cells were measured for the recruitment and tube formation of human umbilical vein endothelial cell (HUVEC) by HUVEC migration assay and tube formation assay, ELISA assay and western blot analysis. In vivo, subcutaneous xenografts in nude mice were used to detect tunorigenicity. Moreover, the expression of RASAL2, VEGFA and CD31 in RCC tissues and xenografts were detect by immunohistochemical (IHC) staining. RESULTS The expression of RASAL2 was downregulated in RCC tissues, and RASAL2 mRNA was inversely correlated with RASAL2 methylation or c-FOS mRNA or VEGFA mRNA in RCC tissues. Overexpression of RASAL2 in 786-O cells could inhibit the recruitment and tube formation of HUVECs, while RASAL2 knockdown (KD) in ACHN cells enhanced the recruitment and tube formation of HUVECs in vitro. Also, overexpression of RASAL2 could inhibit tumorigenecity of xenografts. Mechanistically, RASAL2 KD could enhance the phosphorylation of GSK3 and upregulate the expression of c-FOS and VEGFA. Furthermore, RASAL2 was inversely correlated with VEGFA and CD31 in tissues from human RCC specimens and xenografts. CONCLUSIONS RASAL2 was downregulated in RCC tissues, which could lead to tumor angiogenesis via p-GSK3/c-FOS/VEGFA signaling pathway. Therefore, RASAL2 could be a potential target to prevent patients with RCC from resistance to anti-vascular therapy. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1203-e1204 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Ke Hui More articles by this author Kaijie Wu More articles by this author Jer-Tsong Hsieh More articles by this author Dalin He More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I1 Apr 2018MP54-20 RASAL2 INHIBITS TUMOR ANGIOGENESIS VIA P-AKT/ETS1 SIGNALING IN BLADDER CANCER Kaijie Wu, Ke Hui, Shiqi Wu, Yangyang Yue, and Dalin He Kaijie WuKaijie Wu More articles by this author , Ke HuiKe Hui More articles by this author , Shiqi WuShiqi Wu More articles by this author , Yangyang YueYangyang Yue More articles by this author , and Dalin HeDalin He More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1711AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES RASAL2 is a member of RAS GTPase-activating proteins, but its roles in different cancer types remain controversial. Previously, we have demonstrated RASAL2 could act as a tumor suppressor to modulate epithelial-mesenchymal transition (EMT) and stemness, which were critical for bladder cancer (BCa) recurrence and metastasis. However, its potential roles in tumor angiogenesis of BCa are largely unknown. METHODS In vitro, Two BCa cell lines (253J-BV and 5637 cells) and their sublines with different RASAL2 expression levels were employed to investigate the recruitment and tube formation of human umbilical vein endothelial cell (HUVEC) by HUVEC migration assay and tube formation assay. The expression of VEGFA and its upstream signaling transduction were explored by ELISA assay and western blot analysis. In vivo, subcutaneous xenografts in nude mice were used to detect tumorigenicity. Moreover, the expression of RASAL2, VEGFA and CD31 in xenografts and human BCa tissues was detected by immunohistochemical (IHC) staining. RESULTS RASAL2 overexpression in 253J-BV cells could inhibit the recruitment and tube formation of HUVECs, meanwhile RASAL2 knockdown (KD) in 5637 cells enhanced the recruitment and tube formation of HUVECs in vitro. Consistently, RASAL2 overexpression in 253J-BV cells could suppress tumorigenecity in vivo. Mechanistically, RASAL2 downregulation could enhance the phosphorylation of AKT and then subsequently upregulate the expression of ETS1 and VEGFA, because PI3K inhibitor LY294002 or ETS1 siRNA could rescue the expression of VEGFA in RASAL2 KD cells while AKT activator SC-79 could also rescue the expression of VEGFA in RASAL2 overexpressed cells. Furthermore, RASAL2 was inversely correlated with VEGFA and CD31 in tissues from subcutaneous xenografts and human BCa specimens. CONCLUSIONS Besides the regulation of EMT and stemness, RASAL2 could also inhibit tumor angiogenesis via p-AKT/ETS1 signaling, which may play a critical role in BCa development and progression. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e720 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Kaijie Wu More articles by this author Ke Hui More articles by this author Shiqi Wu More articles by this author Yangyang Yue More articles by this author Dalin He More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Despite the availability of a number of treatment options, certain cases of primary prostate cancer (PCa) will develop into metastatic PCa, in which epithelial‑mesenchymal transition (EMT) serves an important role. Recently, a natural flavonoid known as 2'‑hydroxyflavanone (2HF) exerts remarkable anticancer activity on various types of cancer. Our previous study demonstrated that 2HF could promote apoptosis and inhibit the proliferation of PCa cells, but whether 2HF is involved in the regulation of EMT, and cell migration and invasion in metastatic PCa remains unknown. The present study used two different metastatic PCa cell lines (PC‑3 and DU145) to investigate the effects of 2HF on EMT, and cell migration and invasion. The results demonstrated that 2HF could inhibit EMT, and cell migration and invasion through the Wnt/β‑catenin signaling pathway by suppressing GSK‑3β phosphorylation, β‑catenin expression and transactivation. In conclusion, the present study revealed a novel function of 2HF, which may be used to prevent or treat PCa metastasis.

Krüppel-like factor 5 (KLF5) is frequently deleted and inactivated in prostate cancer, and exerts tumor-suppressing function in prostate cancer cells. However, the function of KLF5 in the apoptosis of prostate cancer cells remains unclear. In the present study, the effect of KLF5 on phorbol 12-myristate 13-acetate (PMA)-induced apoptosis was investigated in prostate cancer LNCaP cells. It was demonstrated that PMA induced the expression of KLF5 at the mRNA and protein level. To identify whether KLF5 regulates the activity of the downstream pathway, stable KLF5 knockdown or overexpression cell lines were constructed with lentivirus harboring shRNA targeting KLF5 or full-length KLF5 in LNCaP cells. Knockdown of KLF5 significantly decreased PMA-induced apoptosis, while cell apoptosis was significantly increased following KLF5 overexpression compared with the corresponding control groups. Consistently, expression of cleaved poly(ADP-ribose) polymerase and caspase-3 induced by PMA was decreased following KLF5 knockdown and increased following KLF5 overexpression. Using the control medium from cells treated with PMA, it was demonstrated that KLF5 is required for the control medium to induce apoptosis. c-Jun N-terminal kinase (JNK) activity is essential for the apoptosis induced by PMA. It was revealed that knockdown of KLF5 decreased, while overexpression of KLF5 increased the phosphorylation of JNK induced by PMA and control medium treatment. Furthermore, inhibition of tumor necrosis factor α (TNFα) decreased KLF5 expression and significantly decreased cell apoptosis induced by PMA, and control medium. This data indicates that KLF5 is essential for the apoptosis induced by PMA in LNCaP prostate cancer cells. Furthermore, KLF5 is essential for activity of the autocrine factor TNFα, which is secreted by cells treated with PMA and mediates the function of PMA-induced apoptosis through regulating the activity of JNK signaling pathway. These results provide novel insights into the complexity of the signaling pathways regulating apoptosis in prostate cancer cells, which could aid in the development of novel treatments for patients with prostate cancer.

OBJECTIVETo explore the role of survivin and PI3K/AKT pathway in the pathogenesis of psoriasis vulgaris (PV).METHODSPlaque-like lesions collected from 22 patients with PV in progressive stage and 18 normal control skin specimens were examined using immunohistochemical staining, Western blotting and real-time quantitative PCR for expressions of survivin, PI3K and AKT in the keratinocytes, and their correlation was analyzed. A small interfering RNA (siRNA) was used to knock down AKT in cultured HaCaT cells, and Western blotting was used to detect the changes in the expression of survivin. RESULTS Compared with normal skin, PV lesions showed obviously up-regulated expressions of survivin, PI3K and AKT in the keratinocytes. Survivin expression was positively correlated with PI3K (r=0.4510, P=0.0351) and AKT (r=0.4423, P=0.0393) in the keratinocytes in PV lesions. In cultured HaCaT cells, siRNA-mediated knockdown of AKT caused down-regulation of survivin expression.CONCLUSIONSurvivin and PI3K/AKT signaling pathway may participate in the occurrence and progression of PV.

Objective To investigate the expressions of the inhibitor of apoptosis protein survivin and signal transducer and activator of transcription 2 (STAT2) in the tissues of the plaque-like lesions of patients with psoriasis vulgaris (PV) in the progressive stage and discuss their correlation. Methods We collected the plaque-like lesion samples and non-lesion samples from 22 PV patients and the normal skin sample from 18 healthy controls. Real-time quantitative PCR was used to evaluate the mRNA levels of survivin and STAT2 in these samples. Western blot analysis was performed to determine the protein expressions of survivin and STAT2. Immunohistochemical staining was also used to detect the expressions of survivin and STAT2. The correlation between survivin and STAT2 in the PV lesions was determined by Pearson's correlation analysis. Results Compared with healthy control skin and PV non-lesion tissues, the mRNA and protein expressions of survivin and STAT2 were significantly elevated in PV lesion tissues, and the mRNA expression of survivin was positively correlated with STAT2 mRNA in PV lesion tissues (r=0.5282). Conclusion The expressions of survivin and STAT2 are up-regulated in skin lesions of PV patients, and their mRNA expressions are positively correlated.

Muscle-invasive or metastatic bladder cancer (BCa) is associated with a very poor prognosis, and the underlying mechanism remains poorly understood. In this study, we demonstrate RASAL2, a RAS GTPase-activating protein (RAS GAP), acts as a tumor suppressor in BCa. First, RASAL2 was downregulated in BCa specimens and inversely correlated with pathological grades and clinical stages. Furthermore, we observed that RASAL2 could inhibit BCa stemness and epithelial–mesenchymal transition (EMT) based on our gain-of-function and loss-of-function experiments. Mechanistically, we found that mitogen-activated protein kinase/SOX2 signaling had a critical role for maintaining the stemness and mesenchymal properties of RASAL2-deficient BCa cells because inhibition of ERK activity or knockdown of SOX2 could reverse these phenotypes. Also, RASAL2 could inhibit BCa tumorigenesis and distant metastasis in vivo . Moreover, there was an inverse correlation between RASAL2 expression and the stemness/EMT status in subcutaneous xenograft and human BCa specimens. Taken together, our data indicate that RASAL2 is a tumor suppressor in BCa, and modulates cancer stemness and EMT for BCa recurrence and metastasis.

Objective To analyze the relationship between hydronephrosis and other clinical features in upper-tract urothelial carcinoma (UTUC),and to explore the potential predictive factors for its diagnosis and treatment.Methods The clinical data of 235 patients with UTUC treated during Jan.2008 and Dec.2015 were retrospectively analyzed,and the different clinical features between patients with and without hydronephrosis were compared.The important clinical indicators for the treatment and prognosis of UTUC were explored.Results The presence of hydronephrosis was significantly correlated with tumor location (P＜0.001),and carcinoma of ureter was more likely to be complicated with hydronephrosis.Moreover,hydronephrosis was related to tumor grade (P=0.004).In multiple analysis,hydronephrosis was an independent risk factor for higher grade of tumor (HR=3.2,P=0.009),and female sex was an independent risk factor for higher stage of tumor (HR =2.5,P=0.005).Conclusion Hydronephrosis is an important predictive factor for the clinical stage and tumor grade of UTUC.