Biostatistics of VHL-Gene Transfection in the Health Informatics Analysis of Renal Cell Carcinoma

Objective. In this paper, we study the role of the VHL gene in regulating the proliferation and apoptosis of renal cell carcinoma, as well as the safety and transfection efficiency of ultrasound microbubble gene transfection technology. Method. We use kidney cancer cell lines as an in vitro research object and apply ultrasound microbubble gene transfection technology to transfect the VHL gene into kidney cancer cell line (786-0). The proliferation and apoptosis of cells were measured to clarify the inhibitory effect of the VHL gene in renal cell carcinoma. After that, pEGFP-VHL was transfected using ultrasonic microbubble and liposome gene transfection techniques, respectively, and the transfection efficiency was measured by immunofluorescence. Results. Compared with untreated and 786-0 cells that are transfected with empty vector, the expression level of VHL gene mRNA in 786-0 cells that are transfected with pcDNA3.1-VHL was significantly increased, and the cell growth inhibition rate was significantly higher. The rate of apoptosis increased significantly. Transfection efficiency of the pEGFP-VHL gene after transfection of 786-0 cells for 48 h: control group 0, liposome group ( 35.55 ± 2.77 ) %, ultrasound microbubble group ( 18.27 ± 2.83 ) %, and two transfection methods on cells. There is no significant difference in the impact of vitality. Conclusion. VHL gene expression can significantly inhibit the proliferation ability of renal cancer cell line 786-0 and promote its apoptosis. VHL gene is a potential target for gene therapy of kidney cancer.

Kidney Cancer Risk Associated with Historic Groundwater Trichloroethylene Contamination

Trichloroethylene (TCE) is a well-documented kidney carcinogen based on a substantial body of evidence including mechanistic and animal studies, as well as reports from occupational settings. However, the cancer risks for those in residential exposures such as TCE contamination in groundwater are much less clear. The objective of this study was to perform a detailed spatio-temporal analysis of estimated residential TCE exposure in New Hampshire, US. We identified kidney cancer cases (n = 292) and age-, gender-matched controls (n = 448) from the Dartmouth-Hitchcock Health System and queried a commercial financial database for address histories. We used publically available data on TCE levels in groundwater measured at contaminated sites in New Hampshire and then modeled the spatial dispersion and temporal decay. We overlaid geospatial residential locations of cases and controls with yearly maps of estimated TCE levels to estimate median exposures over the 5, 10, and 15-year epochs before diagnosis. The 50th–75th percentile of estimated residential exposure over a 15-year period was associated with increased kidney cancer risk (adjusted Odds Ratio (OR) 1.78 95% CI 1.05–3.03), compared to <50th percentile. This finding supports the need for groundwater monitoring of TCE contaminated sites to identify potential public health risks.

Germline HOXB13 mutation p.G84E do not confer an increased bladder or kidney cancer risk in polish population

Introduction The role of HOXB13 in bladder and renal tumorigenesis is unclear. Our goal was to determine the prevalence of HOXB13 p.G84E mutation in bladder and kidney cancer patients from Poland. Materials and methods 1418 patients with bladder cancer and 813 cases with kidney cancer and 4497 controls were genotyped for HOXB13 p.G84E. Results p.G84E mutation of HOXB13 gene was detected in three of 1418 (0.2%) bladder cancer cases and in six of 4497 controls (odds ratio [OR], 1.6; 95% CI 0.39–6.36; p = 0.8). Among 813 kidney cancer cases HOXB13 mutations was reported in three patients (0,4%) (odds ratio [OR], (OR = 2,8; 95% CI 0.69–11.11; p = 0.3). In cases with mutations in the HOXB13 gene, the family history of cancer was negative. Conclusion HOXB13 mutation was not associated with bladder or kidney cancer. Mutation p.G84E in HOXB13 seem not to play a role in bladder and kidney cancer development in Polish patients.

High Expression of JMJD4 Is a Potential Diagnostic and Prognostic Marker of Renal Cell Carcinoma

Histone demethylase JMJD4 is a burgeoning tumor marker, which has been proven to be associated with colon cancer, but the role it plays in kidney cancer has not yet been investigated. In the present study, we evaluated whether JMJD4 can be a prognostic marker of patients with clear cell renal cell carcinoma (ccRCC) using data from public platform and in vitro experiments. Our results revealed that the expression of JMJD4 is higher in cancerous tissue than in normal tissues ( p < 0.001 ). High expression of JMJD4 is associated with a poor overall survival (OS) of ccRCC as compared with low expression of JMJD4 ( p = 0.015 ). JMJD4 showed significant relevance with M stage ( p = 0.016 ), gender ( p = 0.003 ), OS (0.018), disease-specific survival (DSS) (0.007), and percussion free interval (PFI) (0.041). Univariate and multivariate Cox analyses demonstrated that high JMJD4 expression had independent predictive value for OS in ccRCC patients ( hazard ratio HR = 1.563 , 95 % confidence interval CI = 1.055 ‐ 2.316 , and p = 0.026 ). Besides, in vitro experiments confirmed that high expression of JMJD4 can significantly promote the invasion ability ( p < 0.001 ), cloning ability ( p < 0.001 ), and proliferation ( p < 0.001 ) of renal cell carcinoma. In summary, high JMJD4 expression may be a prognostic marker in patients with kidney cancer.

The functional state of the kallikrein-kinin and renin-angiotensin-aldosterone systems in patients with localized kidney cancer

Introduction. The development of a malignant tumor naturally affects renal function. During tumor formation, the renal tissue is destructed either by direct invasion into the parenchyma, or by mechanical change in the renal architecture caused by compression of the renal parenchyma, collecting ducts, tubules, and nephrons. In addition, a tumor can secrete biologically active substances, which have an indirect negative influence the functional state of the organ. Currently, it has been established that kallikrein-kinin and renin-angiotensin-aldosterone systems play an important role in the development of nephropathy of various genesis. At the same time, these systems' role in the development of renal function disorders in the setting of tumor damage has not yet been studied.Purpose of the study. To study changes in the components of the kallikrein-kinin and renin-angiotensin-aldosterone systems in the case of localized kidney cancer.Materials and methods. Forty-five patients diagnosed with T1N0M0 kidney cancer and 13 relatively healthy patients without cancer were examined. The determination of the components of the systems under study was carried out by the kinetic method after chromatography of blood plasma and urine using DEAE-Sephadex A-50 (Amersham Biosciences Corp., Sweden). The indices of angiotensin-1, renin, aldosterone, and cortisol were studied by an indirect method of radioimmunoassay. Statistical processing was carried out using Statistica 8.0 software (StatSoft Inc., IBM Corp., USA) by means of the Student-Fisher test (p < 0.05).Results. The development of kidney cancer is accompanied by a 2.3-fold increase in the activity of kallikrein and other trypsin proteases with a significant deficiency of their inhibitors (p < 0,05). Against this background, there is a 1.3-fold decrease in the cortisol/renin ratio from a 2.9-fold and 2.3-fold increase in the values of the renin/angiotensin-I and cortisol/angiotensin-I interaction ratios, respectively, compared with the normal values of these indicators (p < 0,05).Conclusions. Renal cell carcinoma is accompanied by trespassing of local metabolism with the formation of tubulointerstitial dysfunction and a shift of the proteinase-inhibitory balance towards proteolytic activation.