Association between elevated serum uric acid levels and high estimated glomerular filtration rate with reduced risk of low muscle strength in older people: a retrospective cohort study.

BACKGROUND: We aimed to investigate the interaction between serum uric acid (SUA) levels with estimated glomerular filtration rate (eGFR) to low muscle strength (LMS) among older people in China. METHODS: Cohort data were obtained from China Health and Retirement Longitudinal Study (CHARLS) in 2011 and 2015. A total of 2,822 community-dwelling adults aged 60 and above were enrolled for the follow-up. Serum uric acid was collected after 8 h of fasting, and handgrip strength was measured with a dynamometer. eGFR was calculated with an equation based on the Chinese population. A generalized additive model was employed for interaction analysis and progressively adjusted confounders. RESULTS: During the follow-up, a total of 659 individuals were excluded due to the lack of grip strength data, leaving 2,163 participants for analysis. Despite the protective effect of high uric acid against low muscle strength, especially in older females, it is not statistically significant (OR = 0.69, 95%CI = 0.45-1.04, P = 0.075). Following the progressive adjustment of covariates, the association between higher eGFR and elevated SUA levels remained statistically significant in females, showing a reduced odds ratio with low muscle strength (OR = 0.82, 95%CI = 0.70-0.97, P = 0.021). However, this trend was not observed in male participants. CONCLUSIONS: This Chinese population-based cohort study suggests that among older females, a higher serum uric acid level combined with a higher estimated glomerular filtration rate is linked to a reduced risk of low muscle strength. This implies that the relationship between high serum uric acid levels and the risk of low grip strength might differ by gender.

A novel prognostic prediction model of cuprotosis-related genes signature in hepatocellular carcinoma.

Background: Cuprotosis is a recently discovered copper-dependent cell death mechanism that relies on mitochondrial respiration. However, the role of cuprotosis-related genes (CRGs) in hepatocellular carcinoma (HCC) and their prognostic significances remain unknown. Methods: Based on the recently published CRGs, the LASSO Cox regression analysis was applied to construct a CRGs risk model using the gene expression data from the International Cancer Genome Consortium as a training set, followed by validation with datasets from The Cancer Genome Atlas and the Gene Expression Omnibus (GSE14520). Functional enrichment analysis of the CRGs was performed by single-sample gene set enrichment analysis. Results: Five of the 13 previously published CRGs were identified to be associated with prognosis in HCC. Kaplan-Meier analysis suggested that patients with high-risk scores have a shorter overall survival time than patients with low-risk scores. ROC curves indicated that the average AUC was more than 0.7, even at 4 years, and at least 0.5 at 5 years. Moreover, addition of this CRG risk score can significantly improve the efficiency of predicting overall survival compared to using traditional factors alone. Functional analysis demonstrated increased presence of Treg cells in patients with high-risk scores, suggesting a suppressed immune state in these patients. Finally, we point to the possibility that novel immunotherapies such as inhibitors of PDCD1, TIGIT, IDO1, CD274, CTLA4, and LAG3 may have potential benefits in high-risk patients. Conclusion: We constructed a better prognostic model for liver cancer by using CRGs. The CRG risk score established in this study can serve as a potentially valuable tool for predicting clinical outcome of patients with HCC.

Mechanism of Abnormal Coagulation Induced by Tigecycline in Cancer Patients.

Tigecycline is a broad-spectrum active intravenous antibiotic that is active against methicillin-resistant staphylococcus aureus. In Phase 3 and 4 clinical trials, increased all-cause mortality was observed in patients treated with tigecycline compared to patients in the control group. The reason for the increase is unclear. In this study, we found that tigecycline cause abnormal coagulation in tumor patients, especially in patients with hematological malignancies. The main manifestations were decreased fibrinogen and prolonged activated prothrombin time (APTT), thrombin time (TT), and D-dimer. In addition, through functional studies, we found that tigecycline inhibit platelet adhesion and aggregation, and the coagulation function of patients gradually recover after discontinuation. Gene sequencing results suggested that tigecycline significantly regulate the expression of genes related to platelet function pathways and increase the incidence of single nucleotide polymorphisms and the number of alternative splices in the Chinese hamster ovary (CHO) cells treated with tigecycline. An abnormal function and low numbers of platelets are common in patients with hematological malignancies. Our study can explain the mechanism of abnormal coagulation caused by tigecycline. Additionally, doctors who apply tigecycline to cure infections in tumor patients should be warned.

Drug resistance biomarker ABCC4 of selinexor and immune feature in multiple myeloma.

The treatment of relapse or refractory multiple myeloma (RRMM) is still a big challenge in clinic. Recently, several clinical trials indicated that the XPO1 inhibitor, selinexor could significantly improve the remission rate in MM patients. However, the heterogeneous genetic background greatly influenced the efficiency of selinexor among MM. Here, we tried to characterized the biomarkers associated with selinexor sensitivity by analyzing gene expression data in MM patients. We found the cytogenetic background of selinexor sensitive MM patients was not limited to specific cytogenetic subtypes. In addition, by weighted gene co-expression network analysis (WGCNA), we obtained 10 key genes which showed a strong correlation with the selinexor sensitivity in MM patients. Notably, ABCC4 (MRP4) was the only gene which was both differentially expressed and proved to be clinical prognostic valuable (both for event-free survival and overall survival) in MM patients. We further validated the heterogenous expression of ABCC4 in MM cell lines and its value as a novel indicator for selinexor sensitivity. Moreover, immune infiltration analysis showed that ABCC4 expression had a significantly positive correlation with NK infiltration as well as immunotherapy target TIM-3 (HAVCR2) expression. Collectively, our findings indicated that ABCC4 might be a predictive biomarker of selinexor sensitivity in MM patients, which could be enhanced if combined with immunotherapy drugs such as TIM-3 inhibitor.

Multi-omics analyses of tumor-associated immune-infiltrating cells with the novel immune checkpoint protein tyrosine phosphatase 1B (PTP1B) in extracellular matrix of brain-lower-grade-glioma (LGG) and uveal-melanoma (UVM).

Immune checkpoint inhibitors represented by PD-1 have greatly changed the way cancer is treated. In addition to PD-1, new immune checkpoints are constantly excavated to better treat cancer. Recently, protein tyrosine phosphatase 1B (PTP1B) was identified as a new immune checkpoint and played a critical role in the treatment of tumors by inhibiting the proliferation and cytotoxicity of T cells induced by tumor antigen. To explore the targeting role of PTP1B in precision tumor therapy, we deeply analyzed the expression and prognosis of PTP1B in all tumors. Survival analysis results indicated that PTP1B was highly expressed in most tumor tissues and indicated poor prognosis in acute-myeloid-leukemia (LAML), brain-lower-grade-glioma (LGG), kidney-renal clear-cell-carcinoma (KIRC) and uveal-melanoma (UVM). The methylation status of PTP1B in these four tumors exhibited hypomethylation and mutation landscape showed that PTP1B had its specific characteristics in genomic instability and heterogeneity. The homologous recombination deficiency (HRD) and loss of heterozygosity (LOH) were positive related to PTP1B expression in liver-hepatocellular-carcinoma (LIHC) and kidney-chromophobe (KICH), while the immunescore and immune infiltration displayed a significant positive correlation with PTP1B expression in LGG and UVM. Drug sensitivity tests showed that the PTP1B inhibitor MSI-1436 had a sensitivity effect suppressing tumor cell viability and suggested it enhanced the efficacy of PD-1 inhibitors in cancers.

[Differences of Gut Microbiota Diversity between Patients with Abdominal Aortic Aneurysm and Atherosclerosis].

Objective To investigate the differences of gut microbiota between patients with abdominal aortic aneurysm and atherosclerosis.Methods From December 2018 to June 2019,20 fresh stool samples were collected respectively from the patients with abdominal aortic aneurysm and atherosclerosis treated at the Department of Vascular Surgery,Peking Union Medical College Hospital.The 16S rDNA high-throughput sequencing was employed to compare the composition,abundance,and α and ß diversities of gut microbiota between the two disease groups,and further determine the significantly differential genera.Results The two groups had great similarities in the composition of gut microbiota.There was no statistical difference in α diversity.Although ß diversity did not have statistically significant difference,certain microbial taxa showed differences between the two groups.The LEfSe demonstrated that the abdominal aortic aneurysm group had higher relative abundance of Leuconostocaceae,Ruminococcaceae,Weissella,and Faecalibacterium while lower relative abundance of Firmicuteria,Selenomonadales,and Veillonellaceae.Conclusion The structure of gut microbiota has differences between patients with abdominal aortic aneurysm and atherosclerosis,and sample size should be enlarged to validate the results.

Toward the Cure of Acute Lymphoblastic Leukemia in Children in China.

This study explored results of therapy of children with acute lymphoblastic leukemia (ALL) in China, recent progress, and challenges. Included are a survey of therapy outcomes of ALL in Chinese children nationwide, comparison of these data with global ALL therapy outcomes, analyses of obstacles to improving outcomes, and suggestions of how progress can be achieved. Therapy outcomes at many Chinese pediatric cancer centers are approaching those of resource-rich countries. However, nationwide outcomes still need improvement. Obstacles include suboptimal clinical trials participation, children without adequate health care funding, human resource shortages, especially physicians expert in pediatric hematology and oncology, and social-economic disparities. We suggest how these obstacles have been and continue to be remedied including expanded access to protocol-based therapy, improved supportive care, health care reforms, recruitment of trained personnel, and international collaborations. China has made substantial progress treating children with ALL. We envision even better outcomes in the near future.

Bone marrow infiltrated natural killer cells predicted the anti-leukemia activity of MCL1 or BCL2 inhibitors in acute myeloid leukemia.

Acute myeloid leukemia (AML) is still incurable due to its heterogeneity and complexity of tumor microenvironment. It is imperative therefore to understand the molecular pathogenesis of AML and identify leukemia-associated biomarkers to formulate effective treatment strategies. Here, we systematically analyzed the clinical characters and natural killer (NK) cells portion in seventy newly-diagnosis (ND) AML patients. We found that the proportion of NK cells in the bone marrow of ND-AML patients could predict the prognosis of patients by analyzing the types and expression abundance of NK related ligands in tumor cells. Furthermore, MCL1 inhibitor but not BCL2 inhibitor combined with NK cell-based immunotherapy could effectively improve the therapeutic efficiency via inhibiting proliferation and inducing apoptosis of AML primary cells as well as cell lines in vitro. There results provide valuable insights that could help for exploring new therapeutic strategies for leukemia treatment.

An Immune Risk Score Predicts Survival of Patients with Acute Myeloid Leukemia Receiving Chemotherapy.

PURPOSE: Prediction models for acute myeloid leukemia (AML) are useful, but have considerable inaccuracy and imprecision. No current model includes covariates related to immune cells in the AML microenvironment. Here, an immune risk score was explored to predict the survival of patients with AML. EXPERIMENTAL DESIGN: We evaluated the predictive accuracy of several in silico algorithms for immune composition in AML based on a reference of multi-parameter flow cytometry. CIBERSORTx was chosen to enumerate immune cells from public datasets and develop an immune risk score for survival in a training cohort using least absolute shrinkage and selection operator Cox regression model. RESULTS: Six flow cytometry-validated immune cell features were informative. The model had high predictive accuracy in the training and four external validation cohorts. Subjects in the training cohort with low scores had prolonged survival compared with subjects with high scores, with 5-year survival rates of 46% versus 19% (P < 0.001). Parallel survival rates in validation cohorts-1, -2, -3, and -4 were 46% versus 6% (P < 0.001), 44% versus 18% (P = 0.041), 44% versus 24% (P = 0.004), and 62% versus 32% (P < 0.001). Gene set enrichment analysis indicated significant enrichment of immune relation pathways in the low-score cohort. In multivariable analyses, high-risk score independently predicted shorter survival with HRs of 1.45 (P = 0.005), 2.12 (P = 0.004), 2.02 (P = 0.034), 1.66 (P = 0.019), and 1.59 (P = 0.001) in the training and validation cohorts, respectively. CONCLUSIONS: Our immune risk score complements current AML prediction models.

Effects of Alternative Splicing Events on Acute Myeloid Leukemia.

As suggested by an increasing amount of evidence, there is alternative splicing (AS) modification within malignancy, which is related to cancer occurrence and development. AS within acute myeloid leukemia (AML) has not yet been systematically analyzed yet. This study analyzed the transcriptomic profiling and corresponding clinical data from AML cases based on The Cancer Genome Atlas (TCGA). In addition, the prediction model, along with the splicing network, was used to analyze the prognosis for AML patients according to the seven different AS event types. Among the 34,984 AS events across the 8830 genes, 2896 AS events were detected among 1905 genes, showing marked correlation with the overall survival of patients. The risk scoring model based on all AS event types was the most efficient in identifying the prognosis for AML patients. Meanwhile, the area under the curve at 1-, 3-, 5-year were 0.852, 0.935, 0.955, respectively. At the same time, the splicing regulating network, which was constituted by 21 splicing factor genes as well as 32 AS events related to survival, was characterized. In conclusion, our predictive model constructed based on the AS events accurately predicts the survival for AML patients. In addition, the network between AS events and splicing factor is established, which may serve as a potential mechanism.

Prognosis and regulation of an adenylyl cyclase network in acute myeloid leukemia.

We explored the roles of adenylyl cyclases (ADCYs) in acute myeloid leukemia (AML). Expression ADCYs in AML and their effect on prognosis was analyzed using data from Oncomine, GEPIA and cBioPortal databases. Frequently altered neighbor genes (FANGs) of ADCYs were detected using the 3D Genome Browser, after which the functions of these FANGs were predicted using Metascape tools. Cell viability and apoptosis were assessed using CCK-8 and Annexin V-FITC/PI kits. Expression levels of ADCYs were higher in AML cells lines and in bone marrow-derived mononuclear cells from AML patients than in control cells, and were predictive of a poor prognosis. A total of 58 ADCY FANGs were identified from the topologically associating domains on the basis of the Hi-C data. Functional analysis of these FANGs revealed abnormal activation of the MAPK signaling pathway. Drug sensitivity tests showed that fasudil plus trametinib or sapanisertib had a synergistic effect suppressing AML cell viability and increasing apoptosis. These findings suggest that dysregulation of ADCY expression leads to altered signaling in the MAPK pathway in AML and that the ADCY expression profile may be predictive of prognosis in AML patients.

The Pull-Through Technique for Recanalization of Transjugular Intrahepatic Portosystemic Shunt Dysfunction.

PURPOSE: To evaluate the technical efficacy and safety of the pull-through technique in recanalization of transjugular intrahepatic portosystemic shunt (TIPS) when standard transjugular approach is inaccessible. MATERIALS AND METHODS: A retrospective review of patients underwent TIPS revision via the pull-through technique was performed. Transhepatic directly punctured stent was conducted if the portal vein could not be accessed via standard transjugular approach. Technical success was defined by recanalization of shunt. Clinical success was defined as bleeding interruption and ascites regression without pharmacological support. All patients were followed up by clinical evaluation and Doppler ultrasound. RESULTS: Between January 2010 and December 2016, a total of 63 patients underwent TIPS revision, and 14 of them could not be accessed via standard transjugular approaches owing to stenosis or occlusion of the hepatic vein. The pull-through technique was successful in 13 patients, and one patient underwent parallel TIPS. No procedure-related complication was observed. One patient died of liver failure one week after the procedure. During the follow-up, three patients developed hepatic encephalopathy, and one patient developed TIPS dysfunction again and experienced variceal bleeding. The primary patency rate after TIPS revision was 92% (11/12) at 12 months. CONCLUSION: The pull-through technique was effective and safe for recanalization of TIPS inaccessible via standard transjugular approach.

Systematic Construction and Validation of a Metabolic Risk Model for Prognostic Prediction in Acute Myelogenous Leukemia.

Background: Acute myelogenous leukemia (AML) is a heterogeneous disease with recurrent gene mutations and variations in disease-associated gene expression, which may be useful for prognostic prediction. Methods: RNA matrix and clinical data of AML were downloaded from GEO, TCGA, and TARGET databases. Prognostic metabolic genes were identified by LASSO analysis to establish a metabolic model. Prognostic accuracy of the model was quantified by time-dependent receiver operating characteristic curves and the area under the curve (AUC). Survival analysis was performed by log-rank tests. Enriched pathways in different metabolic risk statuses were evaluated by gene set enrichment analyses (GSEA). Results: We identified nine genes to construct a prognostic model of shorter survival in the high-risk vs. low-risk group. The prognostic model showed good predictive efficacy, with AUCs for 5-year overall survival of 0.78 (0.73-0.83), 0.76 (0.62-0.89), and 0.66 (0.57-0.75) in the training, adult external, and pediatric external cohorts, respectively. Multivariable analysis demonstrated that the metabolic signature had independent prognostic value with hazard ratios of 2.75 (2.06-3.66), 1.89 (1.09-3.29), and 1.96 (1.00-3.84) in the training, adult external, and pediatric external cohorts, respectively. Combining metabolic signatures and classic prognostic factors improved 5-year overall survival prediction compared to the prediction by classic prognostic factors (p < 0.05). GSEA revealed that most pathways were metabolism-related, indicating potential mechanisms. Conclusion: We identified dysregulated metabolic features in AML and constructed a prognostic model to predict the survival of patients with AML.

Identification of a metabolic gene panel to predict the prognosis of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is clonal disease featured by ineffective haematopoiesis and potential progression into acute myeloid leukaemia (AML). At present, the risk stratification and prognosis of MDS need to be further optimized. A prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis for MDS patients based on the identified metabolic gene panel in training cohort, followed by external validation in an independent cohort. The patients with lower risk had better prognosis than patients with higher risk. The constructed model was verified as an independent prognostic factor for MDS patients with hazard ratios of 3.721 (1.814-7.630) and 2.047 (1.013-4.138) in the training cohort and validation cohort, respectively. The AUC of 3-year overall survival was 0.846 and 0.743 in the training cohort and validation cohort, respectively. The high-risk score was significantly related to other clinical prognostic characteristics, including higher bone marrow blast cells and lower absolute neutrophil count. Moreover, gene set enrichment analyses (GSEA) showed several significantly enriched pathways, with potential indication of the pathogenesis. In this study, we identified a novel stable metabolic panel, which might not only reveal the dysregulated metabolic microenvironment, but can be used to predict the prognosis of MDS.

Resection vs. ablation for lesions characterized as resectable-ablative within the colorectal liver oligometastases criteria: a propensity score matching from retrospective study.

BACKGROUND: There has been no prospective or retrospective studies reporting the comparison outcome between surgery and ablation for resectable-ablative (lesions could be treated by resection or complete ablation) colorectal liver oligometastases (CLOM). The purpose of this study was to compare the efficacy and prognostic difference in patients who underwent R0 resection vs. complete ablation within the resectable-ablative CLOM criteria. METHODS: From January 2008 to May 2018, a total of 2,367 patients diagnosed with colorectal liver metastases were included in this observational study. The metastasis was characterized by only limited to liver with number ≤5, size ≤5 cm, and resectable-ablative (lesions could be treated by resection or complete ablation). The evaluated indications, including liver progression-free survival (LPFS), overall survival (OS), survival rates, pattern and number of recurrences, and complications, were compared by using propensity score matching (PSM). The Kaplan-Meier curves were generated, and a log-rank test was performed. The Cox regression model was used for univariate and multivariate analyses to identify predictors of outcomes. RESULTS: A total of 421 consecutive patients were eligible for this study, with 250 and 171 undergoing R0 resection and complete ablation, respectively. PSM identified 145 patients from each group. The 1-, 3-, 5- and 8-year OS rates in the resection group and the ablation group were 95.8% vs. 95.0%, 69.8% vs. 60.1%, 53.6% vs. 42.5%, and 45.1% vs. 32.9% (p = 0.075), respectively. The median LPFS in the resection group was significantly longer than that in the ablation group (35 months vs. 15 months, p = 0.011). No statistical difference was found in LPFS between the two groups when comparing ≤3 cm liver metastases. For liver metastasis >3 cm, the median LPFS in the resection group and ablation group was 11 months and 5 months, respectively (p = 0.001). In terms of high risk of clinical risk score (CRS), the resection group showed longer LPFS than the ablation group (median 18 months vs. 10 months, p = 0.043). CONCLUSION: For patients within the CLOM criteria suggesting that liver metastases were resectable as well as ablative, resection could result in longer liver recurrence-free survival than ablation in cases with size >3 cm or high risk of CRS. But for ≤3 cm liver metastases, their treatment efficacies were comparable.

The Role of the HOXA Gene Family in Acute Myeloid Leukemia.

The HOXA gene family is associated with various cancer types. However, the role of HOXA genes in acute myeloid leukemia (AML) have not been comprehensively studied. We compared the transcriptional expression, survival data, and network analysis of HOXA-associated signaling pathways in patients with AML using the ONCOMINE, GEPIA, LinkedOmics, cBioPortal, and Metascape databases. We observed that HOXA2-10 mRNA expression levels were significantly upregulated in AML and that high HOXA1-10 expression was associated with poor AML patient prognosis. The HOXA genes were altered in ~18% of the AML samples, either in terms of amplification, deep deletion, or elevated mRNA expression. The following pathways were modulated by HOXA gene upregulation: GO:0048706: embryonic skeletal system development; R-HSA-5617472: activation of HOX genes in anterior hindbrain development during early embryogenesis; GO:0060216: definitive hemopoiesis; hsa05202: transcriptional mis-regulation in cancer; and GO:0045638: negative regulation of myeloid cell differentiation, and they were significantly regulated due to alterations affecting the HOXA genes. This study identified HOXA3-10 genes as potential AML therapeutic targets and prognostic markers.

The Effect of Puncture Sites of Portal Vein in TIPS with ePTFE-Covered Stents on Postoperative Long-Term Clinical Efficacy.

PURPOSE: To evaluate the effect of puncture sites of the portal vein in transjugular intrahepatic portosystemic shunt (TIPS) on long-term clinical efficacy. METHODS: A retrospective review was performed, including consecutive 171 patients who underwent TIPS with ePTFE-covered stents. All patients were divided into 3 groups according to the puncture site of the portal vein: intrahepatic bifurcation of the portal vein (group A, n = 88), right branch of the portal vein (group B, n = 48), and left branch of the portal vein (group C, n = 35). The Kaplan-Meier analysis was performed to assess the effect of different puncture sites on primary patency, the incidence of hepatic encephalopathy (HE), and survival. RESULTS: The primary restenosis rate was 29.8% (51/171). The total HE rate was 31.6% (54/171). The cumulative death rate was 19.3% (33/171). The Kaplan-Meier analysis showed that group C versus group A, group C versus group B, and group A versus group B were significantly different on the primary restenosis rate, respectively (χ 2 = 11.49, P = 0.001; χ 2 = 4.54, P = 0.033; and χ 2 = 4.12, P = 0.046), and group C is better than the other two groups. What is more, group C versus group A and group C versus group B were significantly different on the incidence of HE, respectively (χ 2 = 8.07, P = 0.004; χ 2 = 9.44, P = 0.002), and group C is better than the other two groups. There was no significant difference on survival. CONCLUSION: Choosing the left branch of the portal vein as the puncture site to create the shunt in TIPS with ePTFE-covered stents may decrease the incident of primary restenosis and HE significantly.

PRMT5 Circular RNA Promotes Metastasis of Urothelial Carcinoma of the Bladder through Sponging miR-30c to Induce Epithelial-Mesenchymal Transition.

PURPOSE: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial-mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells' EMT and explored their regulatory mechanisms and clinical significance in UCBs. EXPERIMENTAL DESIGN: We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells' EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes, SNAIL1 and E-cadherin, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA). RESULTS: We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis. CONCLUSIONS: CircPRMT5 exerts critical roles in promoting UCB cells' EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.

A Genomic-clinicopathologic Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Bladder Cancer.

Preoperative lymph node (LN) status is important for the treatment of bladder cancer (BCa). Here, we report a genomic-clinicopathologic nomogram for preoperatively predicting LN metastasis in BCa. In the discovery stage, 325 BCa patients from TCGA were involved and LN-status-related mRNAs were selected. In the training stage, multivariate logistic regression analysis was used to developed a genomic-clinicopathologic nomogram for preoperative LN metastasis prediction in the training set (SYSMH set, n=178). In the validation stage, we validated the nomogram using two independent sample sets (SYSUCC set, n=142; RJH set, n=104) with respect to its discrimination, calibration and clinical usefulness. As results, we identified five LN-status-related mRNAs, including ADRA1D, COL10A1, DKK2, HIST2H3D and MMP11. Then, a genomic classifier was developed to classify patients into high- and low-risk groups in the training set. Furthermore, a nomogram incorporating the five-mRNA-based classifier, image-based LN status, transurethral resection (TUR) T stage, and TUR lymphovascular invasion (LVI) was constructed in the training set, which performed well in the training and validation sets. Decision curve analysis demonstrated the clinical value of our nomogram. Thus, our genomic-clinicopathologic nomogram shows favorable discriminatory ability and may aid in clinical decision-making, especially for cN-patients.