MiR-183-5p promotes migration and invasion of prostate cancer by targeting TET1.

BACKGROUND: Prostate cancer (PCa) is one of the common malignant tumors worldwide. MiR-183-5p has been reported involved in the initiation of human PCa, this study aimed to investigate whether miR-183-5p affects the development of prostate cancer. METHODS: In this study, we analyzed the expression of miR-183-5p in PCa patients and its correlation with clinicopathological parameters based on TCGA data portal. CCK-8, migration assay and invasion and wound-healing assay were performed to detect proliferation, migration and invasion in PCa cells. RESULTS: We found the expression of miR-183-5p was significantly increased in PCa tissues, and high expression of miR-183 was positively associated with poor prognosis of PCa patients. Over-expression of miR-183-5p promoted the migration, invasion capacities of PCa cells, whereas knockdown of miR-183-5p showed reversed function. Furthermore, luciferase reporter assay showed TET1 was identified as a direct target of miR-183-5p, which was negatively correlation with miR-183-5p expression level. Importantly, rescue experiments demonstrated TET1 over-expression could reverse miR-183-5p mimic induced-acceleration of PCa malignant progression. CONCLUSION: Our results indicated that miR-183-5p could act as a tumor promoter in PCa and it accelerated the malignant progression of PCa by directly targeting and down-regulating TET1.

Apolipoprotein C1 stimulates the malignant process of renal cell carcinoma via the Wnt3a signaling.

BACKGROUND: Renal cell carcinoma (RCC) is a clinically common tumor in the urinary system, showing an upward trend of both incidence and mortality. Apolipoprotein C1 (APOC1) has been identified as a vital regulator in tumor progression. This study aims to uncover the biological function of APOC1 in RCC process and the underlying mechanism. METHODS: Differential levels of APOC1 in RCC samples and normal tissues in a downloaded TCGA profile and clinical samples collected in our center were detected by quantitative reverse transcription PCR (qRT-PCR). The prognostic value of APOC1 in RCC was assessed by depicting Kaplan-Meier survival curves. After intervening APOC1 level by transfection of sh-APOC1 or oe-APOC1, changes in phenotypes of RCC cells were examined through CCK-8, colony formation, Transwell assay and flow cytometry. Subsequently, protein levels of EMT-related genes influenced by APOC1 were determined by Western blot. The involvement of the Wnt3a signaling in APOC1-regulated malignant process of RCC was then examined through a series of rescue experiments. Finally, a RCC xenograft model was generated in nude mice, aiming to further clarify the in vivo function of APOC1 in RCC process. RESULTS: APOC1 was upregulated in RCC samples. Notably, its level was correlated to overall survival of RCC patients, displaying a certain prognostic value. APOC1 was able to stimulate proliferative, migratory and invasive abilities in RCC cells. The Wnt3a signaling was identified to be involved in APOC1-mediated RCC process. Notably, Wnt3a was able to reverse the regulatory effects of APOC1 on RCC cell phenotypes. In vivo knockdown of APOC1 in xenografted nude mice slowed down the growth of RCC. CONCLUSIONS: APOC1 stimulates the malignant process of RCC via targeting the Wnt3a signaling.

Overexpression of Capns1 Predicts Poor Prognosis and Correlates with Tumor Progression in Renal Cell Carcinoma.

INTRODUCTION: Calpain small subunit 1 (Capns1) has shown its correlation with the metastasis and invasion of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, the expression and function of Capns1 in human renal cell carcinoma (RCC) have not been clarified. This study aimed to examine the expression of Capns1 in RCC tissues and cell lines and to assess its role performed in RCC. METHODS: Capns1 expression was evaluated in 75 pairs of RCC and matched adjacent non-tumor tissues by immunohistochemistry. The prognostic value of Capns1 in RCC was assessed by Kaplan-Meier and Cox regression analyses. The action of Capns1 in the proliferation, adhesion, migration, and invasion of RCC cells and the effects on matrix metalloproteinase (MMP) 2 and 9 expression were evaluated after Capns1 silence. RESULTS: Capns1 expression was significantly higher in RCC tissues compared with the adjacent non-tumor tissues. Multivariate analysis showed that Capns1 overexpression was an independent poor prognostic marker in RCC. The silencing of Capns1 prohibited cell adhesion and impaired the migration and invasion ability of 786-O cells in vitro. Furthermore, Capns1 silence reduced MMP2 and MMP9 expression. CONCLUSION: Capns1 overexpression predicts poor prognosis and correlates with tumor progression in RCC. Capns1 expression might serve a prognostic marker and therapeutic target for RCC.

Resveratrol inhibits the tumor migration and invasion by upregulating TET1 and reducing TIMP2/3 methylation in prostate carcinoma cells.

BACKGROUND: Recently, resveratrol (Res) has been suggested to suppress the migration and invasion of prostate cancer (PCa). In the present study, we aimed to investigate the effects of Res on genomic DNA methylation, as well as the migration and invasion of PCa cells. METHODS: The suppression by Res of the growth of PCa cells was verified through a cytotoxicity assay. In addition, the effects of Res on 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and ten-eleven translocation 1 (TET1) levels were assessed, and the cell migration and invasion were also determined. The expressions of TET1, tissue inhibitor of metalloproteinases (TIMP) 2, TIMP3, MMP2, and MMP9 were detected through Western blot analysis. Afterward, TET1 was silenced using lentiviral short hairpin RNA to examine the effect of TET1 on the Res-triggered inhibition of migration and invasion of PCa cells. RESULTS: Our results showed that Res upregulated the 5hmC and TET1 levels and downregulated the 5mC level. Moreover, Res also inhibited the migration and invasion of PCa cells, promoted the demethylation of TIMP2 and TIMP3 to upregulate their expressions, and suppressed the expressions of MMP2 and MMP9. The silencing of TET1 in the presence of Res showed that Res could exert its effect through TET1. CONCLUSIONS: Our findings indicated that Res inhibited the migration and invasion of PCa cells via the TET1/TIMP2/TIMP3 pathway, which might potentially serve as a target for the treatment of PCa.

Prognostic significance of galectin-1 expression in patients with cancer: a meta-analysis.

BACKGROUND: The prognostic significance of galectin-1 (Gal-1) expression in cancerous patients has been assessed for several years while the results remain controversial. Thus, we performed the first comprehensive meta-analysis to evaluate the prognostic value of Gal-1 expression in cancerous patients. METHODS: We searched Pubmed, Embase and Web of Science to recruit studies on the prognostic impact of Gal-1 expression in cancerous patients. Eighteen studies containing 2674 patients were involved in this meta-analysis until March 30, 2018. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to estimate the effect using random-effects model. RESULTS: The pooled results revealed that high Gal-1 expression in cancer tissue associated with a poor OS (HR = 1.79, 95% CI 1.54-2.08, P < 0.001). In the subgroup of tumor type, it's observed that high Gal-1 expression was significant correlated with poor OS in digestive cancers without heterogeneity (HR = 1.94, 95% CI 1.64-2.30, P < 0.001; fixed-effects model; I2 = 20.1%, P = 0.276). CONCLUSIONS: Our present meta-analysis indicates that high Gal-1 expression might be a predictive factor of poor prognosis in cancers, particularly in digestive cancers.

Capn4 contributes to tumor invasion and metastasis in clear cell renal cell carcinoma cells via modulating talin-focal adhesion kinase signaling pathway.

Calpain small subunit 1 (Capn4) has been shown to correlate with the metastasis/invasion of clear cell renal cell carcinoma (ccRCC). This study aimed to further elucidate the molecular mechanisms underlying Capn4-mediated ccRCC progression. The mRNA expression levels in ccRCC cells were measured by quantitative real-time PCR. The effects of Capn4 on cell adhesion, invasion, and migration were examined by cell adhesion assay, cell invasion assay, and wound-healing assay, respectively. The protein levels were detected by western blot analysis. The effect of Capn4 on cancer metastasis in vivo was assessed in a nude mice xenograft model. It was found that Capn4 was up-regulated in the ccRCC cells, and Capn4 overexpression suppressed cell adhesion activity and increased cell invasion and migration in 786-O cells, while Capn4 silencing increased cell adhesion activity and impaired the invasion and migration ability of Caki-1 cells. Capn4 overexpression also increased the protein level of cleaved talin in 786-O cells, while Capn4 silencing decreased the protein level of cleaved talin in Caki-1 cells. The focal adhesion kinase (FAK)/AKT/MAPK signaling was activated by Capn4 overexpression in 786-O cells, and was inhibited by Capn4 down-regulation in Caki-1 cells. Capn4 overexpression increased the protein levels of matrix metalloproteinase 2 (MMP-2), vimentin, N-cadherin, and down-regulated E-cadherin in 786-O cells, while Capn4 silencing decreased the protein levels of MMP-2, vimentin, N-cadherin, and up-regulated E-cadherin in Caki-1 cells. Capn4 also promoted cancer metastasis in the in vivo nude mice xenograft model. Our results implicate the functional role of Capn4 in ccRCC invasion and migration, which may contribute to cancer metastasis in ccRCC.

Machine learning developed an intratumor heterogeneity signature for predicting clinical outcome and immunotherapy benefit in bladder cancer.

Background: Bladder cancer is a common malignancy with high invasion and poor clinical outcome. Intratumor heterogeneity (ITH) is linked to cancer progression and metastasis and high ITH can accelerate tumor evolution. Our objective is to develop an ITH-related signature (IRS) for predicting clinical outcome and immunotherapy benefit in bladder cancer. Methods: Integrative procedure containing ten machine learning methods was applied to develop an IRS with The Cancer Genome Atlas (TCGA), gene series expression (GSE)13507, GSE31684, GSE32984 and GSE48276 datasets. To evaluate the performance of IRS in predicting the immunotherapy benefit, we also used several predicting scores and three immunotherapy datasets, including GSE91061, GSE78220 and IMvigor210. Results: The predicting model constructed with Enet (alpha =0.2) algorithm had a highest average C-index of 0.69, which was suggested as the optimal IRS. As an independent risk factor for bladder cancer, IRS had a powerful performance in predicting the overall survival (OS) rate of patients, with an area under curve of 1-, 3- and 5-year receiver operating characteristic (ROC) curve being 0.744, 0.791 and 0.816 in TCGA dataset. Bladder cancer patients with low IRS score presented with a higher level of immune-activated cells, cytolytic function and T cell co-stimulation. We also found a lower tumor immune dysfunction and exclusion (TIDE) score, lower immune escape score, higher programmed cell death protein 1 (PD-1) & cytotoxic T-lymphocyte associated protein 4 immunophenoscore, higher tumor mutation burden (TMB) score, higher response rate and better prognosis in bladder cancer with low IRS score. Bladder cancer cases with high IRS score had a higher half maximal inhibitory concentration value of common chemotherapy and targeted therapy regimens. Conclusions: The current study developed an optimal IRS for bladder cancer patients, which acted as an indicator for predicting prognosis, stratifying risk and guiding treatment for bladder cancer patients. Further analysis should be focused on the exploration the differentially expressed genes (DEGs) and related underlying mechanism mediating the development of bladder cancer in different IRS score group.

NAT10 promotes renal ischemia-reperfusion injury via activating NCOA4-mediated ferroptosis.

Ischemia-reperfusion injury (IRI) is a significant contributor to acute kidney injury (AKI) and is associated with substantial morbidity and mortality rates. In this study, we aimed to investigate the role of NAT10 and its ac4C RNA modification in IRI-induced renal injury. Our findings revealed that both the expression level of NAT10 and the RNA ac4C level in the kidneys were elevated in the IRI group compared to the sham group. Functionally, we observed that inhibition of NAT10 activity with Remodelin or the specific knockout of NAT10 in the kidney led to a significant attenuation of IRI-induced renal injury. Furthermore, in vitro experiments demonstrated that NAT10 inhibition and specific knockout of NAT10 in the kidney markedly suppressed global ac4C RNA modification, providing protection against hypoxia/reoxygenation-induced tubular epithelial cell injury and ferroptosis. Mechanistically, our study uncovered that NAT10 promoted ac4C RNA modification of NCOA4 mRNA, thereby enhancing its stability and contributing to IRI-induced ferroptosis in tubular epithelial cells (TECs). These findings underscore the potential of NAT10 and ac4C RNA modification as promising therapeutic targets for the treatment of AKI. Overall, our study sheds light on the critical involvement of NAT10 and ac4C RNA modification in the pathogenesis of IRI-induced renal injury, offering valuable insights for the development of novel AKI treatment strategies.

Knowledge, Attitude, and Practice Toward Varicocele in Patients with Varicoceles: A Cross-Sectional Study in Chinese Patients.

Objective: To explore patients' knowledge, attitude, and practice (KAP) toward varicocele in China and the relationship between treatment selection and KAP. Methods: This cross-sectional study enrolled varicocele patients at the Third Affiliated Hospital of Soochow University (September to October 2023). Structural equation modeling (SEM) was used to explore the relationship between clinical factors and KAP. A score >mean score for each dimension was defined as adequate knowledge, positive attitude, and proactive practice. The patients were grouped according to varicocelectomy vs no surgery. Univariable and multivariable logistic regression analyses were used to identify the factors independently associated with KAP. A structural equation modeling (SEM) analysis was performed to examine how the KAP dimensions influenced each other. Results: Among 502 patients, 44.02%, 35.86%, and 20.12% were ≤30, 31-40, and >40 years old, respectively. Those who underwent varicocelectomy (n=407) had significantly higher knowledge (20 (15-22) vs 0 (0-6), P<0.001), attitude (26 (24-26) vs 14 (10-18), P<0.001), and practice (20 (17-24) vs 8 (6-16), P<0.001) than those who did not. A higher proportion of patients with varicocelectomy were <40 years old, more educated, had higher income, and were unmarried compared with those without surgery (all P<0.001). High school or higher education level and varicocelectomy (irrespective of type) were independently associated with adequate knowledge (all P<0.001). Knowledge, college/bachelor's degree education, and varicocelectomy type (irrespective of type) were associated with positive attitudes (all P<0.05). In the SEM, knowledge directly influenced attitude, knowledge directly influenced practice, and attitude directly influenced practice (all P<0.001). Having knowledge of the subject may direct varicocele patients to varicocelectomy. Conclusion: Chinese patients who underwent varicocelectomy exhibit appropriate KAP regarding varicocele, while non-surgery patients have poorer KAP. These results suggest that patients who did not undergo surgery should nevertheless be properly informed about their disease.

CCL5 promotes the proliferation and metastasis of bladder cancer via the JAK2/STAT3 signaling pathway.

Background: Non-muscle invasive bladder cancer (NMIBC) is one of the most common malignant tumors of the urinary system. There is an urgent need for further studies to elucidate the underlying mechanisms of bladder cancer (BC) progression. It has been observed that C-C chemokine ligand 5 (CCL5) and its receptor C-C chemokine receptor type 5 (CCR5) are expressed abnormally and activated in solid tumors and hematological malignancies, which is gaining increasing attention. However, the underlying mechanism of CCL5 in BC remains unclear. Methods: The expression levels of CCL5 were analyzed by real-time polymerase chain reaction (RT-PCR) and western blot. Proliferation analysis of cells was carried out using Cell Counting Kit-8 (CCK-8). The assessment of the migration was conducted using a wound-healing assay. A Matrigel-coated transwell chamber was used to test cell invasiveness. A subcutaneous transplantation tumor model and tail vein injection pulmonary metastasis tumor model were used to evaluate the proliferation and metastasis of BC cell in vivo. Results: This study showed that CCL5 promotes proliferative, migratory, and tumor-growing BC cells in vitro and tumor metastasizing BC cells in vivo. Moreover, we found that the tumor-promotive role of CCL5 is dependent on activation of the JAK2/STAT3 signaling pathway. Conclusions: CCL5 may play an oncogenic role in BC and may also serve as a potential diagnostic and prognostic biomarker.

Expression of CHL1 in Clear Cell Renal Cell Carcinoma and its Association With Prognosis.

As a member of the L1 family of neural cell molecules, close homologue of L1 (CHL1) has been proved to be downregulated in several human cancers. In the present study, we aimed to assess the expression and prognostic value of CHL1 in clear cell renal cell carcinoma (CCRCC). Immunohistochemistry was performed to detect the expression of CHL1 in tissue microarray chips. Then we compared specific clinicopathologic features in patients with different CHL1 expressions. The correlation between CHL1 expression and overall survival (OS) was evaluated by the Kaplan-Meier method and Cox regression analysis. We found that the expression of CHL1 was significantly lower in CCRCC tissues compared with adjacent normal tissues, which was correlated with TNM stage (P<0.001), Fuhrman grade (P=0.006), and LVI (P=0.004). The Kaplan-Meier survival analysis indicated that CCRCC patients with low CHL1 expression had a poorer OS rate than those with high CHL1 expression (P<0.001). Univariate and multivariate Cox regression analyses suggested that CHL1 was an independent and unfavorable prognostic factor for the OS rate of CCRCC patients. Collectively, low expression of CHL1 might predict poor OS rate of CCRCC.

Cyclin-dependent kinase 1 shows to be a potential genetic target for chemical cystitis.

BACKGROUND: In the present study, we aimed to explore whether common genetic targets or signaling pathways existed in chemical cystitis. METHODS: Gene Expression Omnibus (GEO) database was used to search the related gene expression profiles. The differentially expressed genes (DEGs) were identified by using GEO2R. The DAVID 6.8 Beta and R software were used to perform Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology function analysis of DEGs. The protein-protein interaction network was constructed by STRING 11.0 to reveal the potential gene interactions. The expression of cyclin-dependent kinase 1 (Cdk1) at the messnger RNA (mRNA) and protein levels was examined by real-time polymerase chain reaction (PCR) and Western blot analysis analysis, respectively. RESULTS: The GEO database was searched, and the gene expression profiles of GSE55986 and GSE68539 were downloaded. A total of 262 DEGs and 356 DEGs were identified from GSE55986 and GSE68539, respectively. We found that the p53 signaling pathway might play a key role in the development of chemical cystitis, and Cdk1 acted as a crucial gene in the p53 signaling pathway. Moreover, the experimental results of real-time PCR and Western blot analysis analysis demonstrated that the expression of Cdk1 at the mRNA and protein levels in cystitis tissues was significantly increased in different animal models of chemical cystitis compared with the control group. CONCLUSION: Cdk1 might be a potential pathogenic genetic target for chemical cystitis.

MiRNA-124 regulates the sensitivity of renal cancer cells to cisplatin-induced necroptosis by targeting the CAPN4-CNOT3 axis.

BACKGROUND: Currently, drug-resistance is a major challenge in the treatment of renal cancer. Although microRNAs (miRNAs) have been reported to contribute to the incidence of drug resistance in renal cancer, the bio-functional roles and underlying regulatory mechanisms of novel miRNAs in cisplatin resistance remain largely unclear. METHODS: In this study, miRNA microarray analysis was applied to evaluate miRNA changes induced by cisplatin on RCC (renal cell carcinoma) cell lines. Then, Caki-1 and 786-0 cells were transfected with miR (miRNA)-124 mimics to observe cisplatin resistance in RCC cell lines after up-regulation of miR-124. TargetScan was used to identify putative protein-coding gene targets of miR-124. Further, the interaction between calpain small subunit 1 (Capn4) and CCR4-NOT transcription complex subunit 3 (CNOT3) was detected by quantitative real-time PCR (qPCR) and western blotting, and confirmed by co-immunoprecipitation. The effect of Capn4 and/or CNOT3 on cell viability and half maximal inhibitory concentration (IC50) value of miR-124 overexpressed Caki-1 and 786-O cells to cisplatin was evaluated using the Cell Counting Kit-8 (CCK-8) assay. And the effect of Capn4 and/or CNOT3 on the level of necroptosis in miR-124 overexpressed Caki-1 and 786-O cells to cisplatin was evaluated by flow cytometric analysis. Then, four groups of 786-0 cells (miR-124, miR-124+ Capn4, miR-124+ CNOT3, miR-124+ Capn4+ CNOT3) were inoculated into nude mice to observe the effect of cisplatin on tumor formation. RESULTS: miR-124 was found to be markedly elevated in renal cancer cells by cisplatin. Functionally, the overexpression of miR-124 reduced the sensitivity of renal cancer cells to cisplatin and CAPN4 was found to be a direct target of miR-124, which can negatively regulated CAPN4 expression. Moreover, ectopic expression of CAPN4 reversed the impairment of miR-124 on cisplatin-sensitivity and cisplatin-induced necroptosis. Mechanically, the present study revealed that CAPN4 could directly interact with CNOT3 and promote its degradation, and that the cisplatin-resistant phenotype was reversed by up-regulation of CNOT3. CONCLUSIONS: Therefore, miR-124 is an important inhibitor in cisplatin-induced necroptosis, and the miR-124-CAPN4-CNOT3 signaling axis plays a critical role in the emergence of cisplatin-resistance.

A novel circular RNA (hsa_circRNA_102336), a plausible biomarker, promotes the tumorigenesis by sponging miR-515-5p in human bladder cancer.

Bladder cancer (BC) ranks as the ninth common human tumor in the world with an increasing incidence. Circular RNAs (circRNAs) have been revealed to exhibit promotive or suppressive impacts on tumor progression of various human cancers, including BC. However, due to the variety of circRNAs, the whole circRNAs network in BC remains unclear. In our study, differentially expressed circRNAs between BC and normal samples in GSE92675 dataset was analyzed by microarray. Circ_102336 was identified to be sharply increased in both BC tissue samples and cell lines, and increased circ_102336 is correlated with a worse overall survival rate of BC patients. Overexpression of circ_102336 dramatically increased the cell proliferation viability of T24 and 5637 cells, while knockdown of circ_102336 exhibited opposite effects. Moreover, circ_102336 knockdown could increase the sensitivity of T24 and 5637 cells to CDDP. In mechanism, circ_102336 was demonstrated to directly bind to and negatively regulate miR-515-5p. Inhibition of miR-515-5p reversed the repressive effects of si-circ_102336 on BC cell proliferation viability. KEGG analysis showed that ATP-binding cassette (ABC) transporters and apoptosis were the major two pathways associated with circ_102336/miR-515-5p axis. therefore, we suggested that circ_102336 indirectly regulate apoptosis and ABC transport pathways through miR-515-5p to finally modulate BC cell proliferation and chemo-resistance.

Atorvastatin inhibits pancreatic cancer cells proliferation and invasion likely by suppressing neurotrophin receptor signaling.

BACKGROUND: Pancreatic cancer (PC) is aggressive and with poor clinical prognosis. However, mechanisms underlying the aggressiveness of PC remain unclear. Increasing evidence indicates that cholesterol, a major source of bio-energy, is required for the progression of human cancers including PC. Therefore, this study aimed to investigate the anti-tumor effect of atorvastatin, a widely used lipid-lowering agent that blocks the production of cholesterol, on human PC. METHODS: We firstly assessed the impacts of atorvastatin on the proliferation, apoptosis, cell cycle distribution, migration and invasion of human PC cells PANC-1 and SW1990. Furthermore, we studied the effects of atorvastatin on neurotrophin receptor signaling, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and their downstream receptors tropomyosin receptor kinase (Trk) Trk A, Trk B and Trk C in human PC cells. RESULTS: Atorvastatin significantly inhibited the proliferation, migration and invasion, and induced G1-phase cell cycle arrest and apoptosis in both PANC-1 and SW1990 cells. Meanwhile, atorvastatin treatment remarkably suppressed the expression of NGF, BDNF, and NT-3 as well as that of their downstream receptors Trk A and Trk C. CONCLUSIONS: These results provide evidence that atorvastatin inhibits the proliferation, migration and invasion ability of human PC cells, and atorvastatin may exert the anti-tumor effect in PC via the inhibition of neurotrophin signaling pathway.

Mucinous tubular and spindle cell carcinoma of the kidney: Five case reports and review of the literature.

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare and polymorphic tumor, which has been previously considered to be a low-grade malignancy, predominantly occurring in women. To the best of our knowledge, MTSCC with bladder metastasis has never been reported. The current study presents five adult cases of MTSCC that included three male and two female patients. Among the male cases, two were of advanced stage, one with MTSCC and renal chromophobe cell carcinoma with bladder metastasis and the other with MTSCC with invasion of the renal vein. The other three cases with small masses were at an early stage. All five cases had a good prognosis and were without recurrence after several years of follow-up. A 70-year-old male with intermittent gross hematuria, intermittent renal colic, and groin radiation pain for a year (case 1), was incidentally detected to have a left renal density mass by total abdominal enhanced computed tomography scans. In the other four cases, renal masses were found by B-ultrasound. The patient in case 1 underwent a retroperitoneal laparoscopic radical nephroureterectomy with bladder cuff resection and transurethral resection of the bladder tumor, and received gemcitabine hydrochloride via intravesical instillation therapy plus cisplatin chemotherapy every 3 months. The patient in case 2 underwent an open left radical nephrectomy and renal pedicle lymph node dissection. The other three patients underwent a laparoscopic radical nephrectomy. All five patients had no recurrence or new metastasis in other organs after follow-up. In conclusion, the incidence of MTSCC in men and women is not as disparate as reported in previous publications. The characteristics of the images of the five adult cases in the present study showed a considerable consistency, with only minor differences. The malignancy and prognosis of MTSCC are still controversial, and thus inclusion and review of more cases is required to reach a definite final conclusion. Sunitinib and gemcitabine chemotherapy in combination with cisplatin may be effective for the therapy of MTSCC patients with metastasis, but a larger range of treatments needs to be identified.

Prognostic value of pretreatment neutrophil count in metastatic renal cell carcinoma: a systematic review and meta-analysis.

Background: In recent years, inflammation has become widely recognized as a crucial component in tumor development and progression. Neutrophils are one of the most common inflammatory markers during hematological examinations. The prognostic value of neutrophils in metastatic renal cell carcinoma (mRCC) remains inconsistent. The aim of this meta-analysis is to evaluate the prognostic value of pretreatment neutrophil count in patients with mRCC. Methods: PubMed, Web of Science and Embase were searched for data on the association between pretreatment neutrophil count and mRCC prognosis up to October 7, 2017. We sorted out relevant studies and extracted the hazard ratio (HR) and its 95% confidence interval (CI) for overall survival (OS) and progression-free survival (PFS). Results: A total of 13 studies containing 3,021 patients with mRCC were summarized in the present meta-analysis. An elevated pretreatment neutrophil count yielded a worse OS (HR=2.17, 95% CI=1.68-2.79, P<0.001) and PFS (HR=1.78, 95% CI=0.91-3.49, P<0.001). Furthermore, we performed a subgroup analysis based on cut-off value, ethnicity, treatment method and analysis type. As a result, the association between pretreatment neutrophil count and survival was statistically significant in the subgroups of cut-off value, ethnicity, treatment method and analysis type. Conclusion: Our results show that the pretreatment neutrophil count is associated with mRCC outcomes and can be used as a valuable inflammatory marker for prognosis monitoring.

Systemic inflammation response index predicts prognosis in patients with clear cell renal cell carcinoma: a propensity score-matched analysis.

PURPOSE: In the present study, we aimed to evaluate the prognostic significance of the systemic inflammation response index (SIRI), which was defined based on peripheral blood counts of neutrophils, lymphocytes, and monocytes, in patients with localized or locally advanced clear cell renal cell carcinoma (CCRCC). PATIENTS AND METHODS: The prognostic value of SIRI was evaluated in a primary cohort consisting of 414 patients with localized or locally advanced CCRCC and then further validated in an independent cohort composed of 168 patients. RESULTS: Kaplan-Meier survival analyses of both cohorts revealed that CCRCC patients with high SIRI levels exhibited poorer overall survival (OS) and cancer-specific survival (CSS) compared with those with low SIRI levels. Furthermore, univariate and multivariate analyses identified SIRI as a significant independent predictor for both OS (HR: 4.853; 95% CI: 2.362-9.972; P<0.001) and CSS (HR: 5.913; 95% CI: 2.681-13.040; P<0.001). Following propensity score matching analysis, SIRI remained an excellent predictor for both OS and CSS. The area under the curve for SIRI was larger than that of the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score in both cohorts. CONCLUSION: SIRI might be a better prognostic predictor than PLR, NLR, MLR, and MSKCC score in patients with localized or locally advanced CCRCC. INSTITUTIONAL REVIEW BOARD APPROVAL NUMBER: (2010) Scientific Research Project No. 39.

RASSF1A promoter methylation correlates development, progression, and poor cancer-specific survival of renal cell carcinoma: trial sequential analysis.

BACKGROUND: This meta-analysis evaluated the clinicopathologic and prognostic significance of RASSF1A promoter methylation in renal cell carcinoma (RCC). MATERIALS AND METHODS: The ORs or HRs and their 95% CIs were calculated. Trial sequential analysis was conducted. RESULTS: Twenty-two articles that included 1,421 patients with RCC and 724 controls were identified. RASSF1A promoter methylation correlated with RCC in tissue, blood, and urine samples. On multivariate analysis, RASSF1A promoter methylation was associated with tumor grade (grade 3-4 vs 1-2: OR=3.59), clinical stage (stage 3-4 vs 1-2: OR=2.15), T classification (pT2-4 vs pT1: OR=2.66), histologic subtypes (papillary vs clear cell: OR=2.91), and cancer-specific survival (HR=1.78), but it was not linked to age, gender, lymph node status, distant metastasis, or overall survival. The Cancer Genome Atlas data also showed that RASSF1A methylation was significantly more likely to be seen in papillary vs clear-cell RCC (OR=23.19). CONCLUSION: RASSF1A promoter methylation may be associated with the development and progression of RCC, as well as poor cancer-specific survival. Methylation was more frequent in papillary vs clear-cell RCC. More studies are needed to confirm these findings in blood or urine samples.