BackgroundRenal cell carcinoma accounts for 2–3% of all cancers and metastasis increased the malignancy of renal cancer. However, the role of methylation in metastasis of renal cancer is poorly understood.MethodsWe performed targeted gene array to compare the differential expressions of methylation regulated genes in metastatic and primary renal cancer tissues. Quantitative methylation specific PCR was performed to examine the CpG methylation levels of Runt related transcription factor 3 (RUNX3) and transforming growth factor (TGF)-β. Western blot was performed to detect the expression of target genes. Murine xenograft renal cancer model was established to assay gene expression, methylation level, tumor growth and animal survival in vivo.ResultsRUNX3 and TGF-β levels were decreased in metastatic renal cancer tissues as a result of their CpG methylation. Metastatic xenograft model displayed decreased expression levels of RUNX3 and TGF-β and higher CpG methylation levels, bigger tumor size and shorter survival time, all which were restored by treatment with a methylation inhibitor.ConclusionsHypermethylation in CpG islands promotes metastasis of renal cancer and is associated with TGF-β and RUNX3 inhibition.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0554-7) contains supplementary material, which is available to authorized users.
Objective: The roles of long non-coding RNAs (lncRNAs) in the diagnosis of clear cell renal cell carcinoma (ccRCC) are still not well-defined. We aimed to identify differentially expressed lncRNAs and mRNAs in plasma of ccRCC patients and health controls systematically.Methods: Expression profile of plasma lncRNAs and mRNAs in ccRCC patients and healthy controls was analyzed based on microarray assay. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based approaches were used to investigate biological function and signaling pathways mediated by the differentially expressed mRNAs. SOCS2-AS1 was selected for validation using Real-Time PCR. The differentially expressed lncRNAs and mRNAs were further compared with E-MTAB-1830 datasets using Venn and the NetworkAnalyst website. The GEPIA and ULCAN websites were utilized for the evaluation of the expression level of differentially expressed mRNA and their association with overall survival (OS).Results: A total of 3,664 differentially expressed lncRNAs were identified in the plasma of ccRCC patients, including 1,511 up-regulated and 2,153 down-regulated lncRNAs (fold change ≥2 and P < 0.05), respectively. There were 2,268 differentially expressed mRNAs, including 932 up-regulated mRNAs and 1,336 down-regulated mRNAs, respectively (fold change ≥2 and P < 0.05). Pathway analysis based on deregulated mRNAs was mainly involved in melanogenesis and Hippo signaling pathway (P < 0.05). In line with the lncRNA microarray findings, the SOCS2-AS1 was down-regulated in ccRCC plasma and tissues, as well as in cell lines. Compared with the E-MTAB-1830 gene expression profiles, we identified 18 lncRNAs and 87 mRNAs differently expressed in both plasma and neoplastic tissues of ccRCC. The expression of 10 mRNAs (EPB41L4B, CCND1, GGT1, CGNL1, CYSLTR1, PLAUR, UGT3A1, PROM2, MUC12, and PCK1) was correlated with the overall survival (OS) rate in ccRCC patients based on the GEPIA and ULCAN websites.Conclusions: We firstly reported differentially expressed lncRNAs in ccRCC patients and healthy controls systemically. Several differentially expressed lncRNAs and mRNAs were identified, which might serve as diagnostic or prognostic markers. The biological function of these lncRNAs and mRNAs should be further validated. Our study may contribute to the future treatment of ccRCC and provide novel insights into cancer biology.
To evaluate the effect of glandular differentiation (GD) on tumor recurrence and progression of pT1 bladder urothelial carcinoma (UC). We performed a retrospective analysis of 82 bladder urothelial carcinoma with glandular differentiation (UCGD) patients which was pathologically diagnosed as pT1, 166 patients of pT1 UC of bladder without histologic variants served as controls. Patients of UCGD were more likely to have higher recurrence (P = 0.002) rate and higher progression rate (P < 0.001). Moreover, UCGD and a poor 5 -year overall survival (OS) (P = 0.02) while there was no difference in cancer-specific survival (CSS) (P = 0.062) between two groups. According to univariate analysis, largest tumor size (HR 1.502, CI 1.158–1.861, P = 0.029), UCGD (HR 1.787, CI 1.298–2.552, P = 0.001), lymphovascular invasion (LVI) (HR 1.226, CI 1.013–1.945, P = 0.039). UCGD (HR 1.367, CI 1.115–1.853, P = 0.038) and LVI (HR 1.416, CI 1.120–2.254, P = 0.013) were prognostic factors associated with disease recurrence and progression, respectively. Additionally, Additionally, UCGD significantly influence disease recurrence (HR 1.871, CI 1.338–2.589, P < 0.001) and progression (HR 1.462, CI 1.138–2.393, p = 0.007). Similarly, LVI significantly influence disease recurrence (HR 1.356, CI 1.053–2.174, P = 0.042) and progression (HR 1.348, CI 1.052–1.944, p = 0.022) in multivariate analysis. UCGD is significantly associated with higher recurrence and progression rate in patients with newly diagnosed pT1. Recurrent cases should be performed radical cystectomy (RC) earlier.
Background: We aimed to evaluate the prognostic significance of high expression of the miR-200 family of microRNAs in bladder cancer. Methods: Studies on the correlation between the miR-200 family and prognosis in patients with bladder cancer were searched in databases. Combined hazard ratios (HRs) were calculated based on HRs and 95% confidence intervals (CIs) for overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS). Cochranes Q test and the I 2 statistic were utilized to assess heterogeneity across the included studies. Potential publication bias was analyzed by Begg and Egger tests. The meta-analysis was conducted using RevMan 5.3 and Stata SE12.0. Results: Data from a total of 1150 patients from 8 studies were extracted. The meta-analysis revealed that high expression of the miR-200 family was correlated with better OS (pooled hazard ratio: 0.50, 95% confidence interval: 0.40–0.62), CSS (pooled hazard ratio: 0.36, 95% confidence interval: 0.22–0.59) and RFS (pooled hazard ratio: 0.48, 95% confidence interval: 0.36–0.65). Both Begg test and Egger test verified no publication bias within the included cohorts. Conclusion: The high expression of the miR-200 family is strongly associated with better prognosis in bladder cancer patients, which will improve bladder cancer management in clinical practice.
Background: The prognostic role of squamous differentiation in upper urinary tract urothelial carcinoma (UTUC) is still unclear. This article describes the impact of squamous differentiation on prognosis and intravesical recurrence of patients with primary UTUC treated with radical nephroureterectomy (RNU). Methods: Totally, we retrieved (I) 669 histologically confirmed UTUC patients without histologic variants; (II) 101 UTUC patients with squamous differentiation in our institution, dating from April 2003 to April 2016. The clinical pathological characteristics and survival outcomes were compared between these two cohorts. Results: In our study, 13% UTUC patients were detected with squamous differentiation. The mean age of all the patients examined was 66, of whom 70% were males. Squamous differentiation significantly associated with tumor stage, tumor grade and lymphovascular invasion. The Kaplan-Meier and Cox regression analyses showed that presence of squamous differentiation was correlated with shorter cancer specific survival of UTUC patients. The 5-year cancer specific survival rates were 47% for squamous differentiation-present patients and 63% for squamous differentiation-absent patients. UTUC patients with squamous differentiation showed a higher frequency of high-grade disease in advanced stage (pT2/pT3/ pT4), while the discrepancy was not shown in early stage (pTa/pT1). Intravesical recurrence was observed in 27% patients. We found that intravesical recurrence had little impact on the cancer specific survival of squamous differentiation-present patients, yet it tended to decrease cancer specific survival among squamous differentiation-absent patients. Conclusions: The presence of squamous differentiation in UTUC patients was a vital prognostic factor for cancer specific survival and correlated with intravesical recurrence after receiving RNU.
Rationale:Extramedullary plasmacytoma (EMP) a rare plasma cell disorder and is frequently associated with plasma cell bone marrow infiltration. Most EMPs involve mucosal lymphoid tissue, especially in the nasopharyngeal area, respiratory tract, and head and neck region. Primary involvement of the kidney is exceedingly rare.Patient Concerns:A 14-year-old girl was admitted in our hospital with intermittent right upper quadrant pain for 1 month and recent (1 day) progressive deterioration. There was a mass found by ultrasonography in the right kidney and subsequent abdominal computed tomography scan revealed a 3 cm mass within the right kidney.Diagnoses:Pathology revealed typical histology of plasmacytoma and immunohistochemistry revealed the expression of CD138, CD45, vimentin, and Kappa light chain.Interventions:The patient successfully underwent radical nephrectomy with an uneventful recovery. She received no chemotherapy or radiotherapy after surgery.Outcomes:There was no recurrence or metastasis during a 22-month follow-up.Lessons:Our case study demonstrated that renal EMP with a relatively indolent clinical course, if detected at an early stage, can be treated by radical nephrectomy without adjuvant therapy. Generally, the clinical outcome and prognosis of EMP are favorable
Many studies have evaluated the correlation between peptidylarginine deiminase 4 (PADI4) -92C/G polymorphism and rheumatoid arthritis (RA), but the results remain inconclusive. Therefore, we performed a meta-analysis in the Chinese population to provide comprehensive data on the association between PADI4 -92C/G polymorphism and RA. Eligible studies published before May 2016 were identified in PubMed and Chinese databases. The strengths of these associations were assessed by pooled odds ratios (OR) and 95% confidence interval (CI). Eight studies documenting a total of 1351 RA cases and 1585 controls were included in this meta-analysis. In the overall analysis, a significant association between the PADI4 -92C/G polymorphism and RA was found in the Chinese population (G vs C: OR=1.32, 95%CI=1.02–1.71; GG+CG vs CC: OR=1.75, 95%CI=1.20–2.53). The subgroup analyses stratified by geographic area(s) and source of controls revealed significant results in South China, in hospital-based studies and population-based studies. In summary, this meta-analysis suggested that PADI4 -92C/G polymorphism may be associated with the RA incidence in the Chinese population, especially for South China. Further studies conducted on other ethnic groups are required for definite conclusions.
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