Kidney Cancer Patients Research Articles

Germline BRCA1 and BRCA2 mutations and the risk of bladder or kidney cancer in Poland

IntroductionThe role of the BRCA1 and BRCA2 genes in bladder and renal tumorigenesis is unclear. Our goal was to determine the prevalence of specific founder mutations genes BRCA1 (5328 insC, C61G and 4153 delA) and BRCA2 (C5972T) mutations in bladder and kidney cancer patients from Poland.Materials and methodsWe genotyped 1028 patients with bladder cancer and 688 cases with kidney cancer and two control groups.ResultsA BRCA1 mutation (all variants combined) was detected in peripheral blood leukocytes in 5 out of 1028 (0.5%) bladder cases and in 17 of 4000 controls (0.4%) (odds ratio [OR], (OR = 1.1; 95% CI 0.42–3.11; p = 1.0). Among 688 unselected kidney cancer cases a BRCA1 mutations was reported in three patients (0.4%) (OR = 1.0; 95% CI 0.29–3.51; p = 1.0). The mutation C5972T in BRCA2 was observed in 54 bladder cancer patients (5.2%) and in 159 of 2791 healthy controls (5.7%) (OR = 0.9; 95% CI 0.66–1.26; p = 0.6). Fifty kidney cancer cases carried a BRCA2 mutation (7.3%) (OR = 1.3; 95% CI 0.93–1.80; p = 0.1).ConclusionIn conclusion, we found no difference in the prevalence of BRCA1 and BRCA2 founder mutations between cases and healthy controls. The mutations BRCA1 and BRCA2 seem not to play a role in bladder and kidney cancer development in Polish patients.

361 Short Term Outcomes of Urological Cancers During COVID-19, an Analysis of the COVIDSurg-Cancer Study

AimWe assessed the short-term outcomes and characteristics of urological cancer patients operated on during the COVID-19 pandemic. This is the first time these outcomes are assessed in urological patients on a large scale.MethodAll bladder, kidney, and prostate cancer patients who underwent elective cancer surgery between March 2020 and July 2020 in the international COVIDSurg-Cancer collaborative database were included in the study. The primary outcome was 30-day mortality. Secondary outcomes were respiratory complications within 30-days and the factors associated with COVID-19 infection.ResultsA total of 1,902 patients were included in the study. A total of 21 (0.1%) mortalities and 40 (0.2%) respiratory complications (acute respiratory distress syndrome or pneumonia) were observed within 30-days of operation. Mortality was more likely in patients aged 80 or above, ASA grade 3 or 4, ECOG grade 1 or above, undergoing major surgery, and amongst patients who had concurrent COVID-19 infection (OR 31.9, 95%CI 12.4–81.42, p<0.001; univariable logistic regression). Respiratory complications were more likely in patients aged over 70, from an area with high community risk, with a revised cardiac risk index of 1 or higher or with a concurrent COVID-19 infection (OR 40.6, 95%CI 11.41–144.45, p<0.001; multivariate). A total of 42 (0.2%) patients were diagnosed with COVID-19 during their inpatient stay; designated COVID-19 sites were not associated with increased COVID-19 infections.ConclusionsMajor urological cancer surgeries are safe to perform during the COVID-19 pandemic on well-selected patients with appropriate risk-stratification. Concurrent COVID-19 infection is associated with a higher risk of mortality and respiratory complications.

Partial vs. radical nephrectomy in non-metastatic pT3a kidney cancer patients: a population-based study.

The aim of this study was to test for differences in cancer specific mortality (CSM) rates between radical nephrectomy (RN) and partial nephrectomy (PN) in pT3a nmRCC patients. Within the surveillance, epidemiology, and end results database (2005-2016), 13,177 pT3a patients treated with either PN or RN were identified. Before and after 1:2 ratio propensity score (PS)-match between PN and RN patients, cumulative incidence plot and competing risks regression (CRR) were used to test differences in CSM and other cause mortality (OCM) rates. Relative to PN (N.=1615, 22.5%), RN patients harbored higher tumor size (72 vs. 38 mm; >70 mm 51 vs.10%), of more aggressive histology, collecting duct (0.4 vs. 0.2%) and sarcomatoid (2.3 vs.0.8%), of higher grade (51.0 vs. 37.5%). After PS-matching and OCM adjustment, 5-year CSM was 3-fold higher after RN than PN (P<0.01). Similarly, after PS matching and CSM adjustment, also 5-year OCM rates were higher after RN (HR: 1.59, P=0.0003). PN does not appear to compromise the oncological outcomes in patients with pT3a or high-grade renal masses when compared with RN. Therefore, these concerns should not deter a surgeon from attempting PN when otherwise technically feasible.

Risk-group Classification by Recursive Partitioning Analysis of Patients Affected by Oligometastatic Renal Cancer Treated with Stereotactic Radiotherapy

AimsDue to the absence of consensus on metastases-directed treatment in kidney cancer, we conducted an analysis of patients treated with stereotactic radiotherapy (SRT) on cranial or extracranial metastases to classify them in survival class risk according to pre-treatment characteristics. Materials and methodsWe included oligometastatic kidney cancer patients treated with SRT on up to five metastases. Concomitant systemic treatment was allowed. End points included overall survival and the binary classification tree approach with recursive partitioning analysis was applied to stratify patients into overall survival risk groups. ResultsIn total, 129 patients were treated on 242 metastases. The brain was the most common site (34.71%), followed by lung (25.62%). With a median follow-up of 19.4 months, 1- and 3-year overall survival were 82.62 and 55.11%. The recursive partitioning analysis identified four prognostic classes. Class 1 included patients aged ≤ 65 years treated on extracranial metastases, with 3-year overall survival of 82.66%. Class 2 included patients aged > 65 years, without history of metastatic bone disease, treated on extracranial metastases, with a 3-year overall survival of 67.91%. Patients aged > 65 years and a history of bone disease, treated on extracranial metastases, were classified as class 3, with a 3-year overall survival of 37.50%. Class 4 included patients treated on brain metastases, with a 3-year overall survival of 9.70%. ConclusionWe produced a stratification model that can predict survival of oligometastatic kidney cancer patients treated with metastases-directed SRT. Site of disease, patient’s age and presence of bone disease can help clinicians in the decision-making process.

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

IntroductionThe 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 methods1418 patients with bladder cancer and 813 cases with kidney cancer and 4497 controls were genotyped for HOXB13 p.G84E.Resultsp.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.ConclusionHOXB13 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.

Examining the Relationship between Depression, Anxiety and Stress in Kidney Cancer Patients.

Cancer of the kidney is one of the 10 most common cancers found globally. Overall, it is the fourth most common cancer in men and the eighth most common cancer in women. Many kidney cancer patients experience psychologic problems and reactions. The present study examined relationship between anxiety, depression, and perceived stress symptoms in kidney cancer patients. Cross-sectional data were obtained from the patients diagnosed with kidney cancer. All participants completed sociodemographic form, Hospital Anxiety and Depression form, and Perceived Stress Scale. Statistical analysis was exercised using the Student's t-test, Chi-squared test (χ2), Fischer's exact test, ANOVA, Mann-Whitney U test, and Kruskal-Wallis one-way variance analysis. A total of 250 patients participated in the study. The mean age was 57.4 years (SD 6.4, range = 25-76 years). The majority of patients were males (73%) and married (218). Anxiety symptoms were determined in 91.2% patients, depression symptoms in 87.2% patients, and perceived stress symptoms in 93.6% patients. The mean scores of Hospital Depression and Anxiety Scale (HADS)-Anxiety, HADS-Depression, and HADS-Perceived Stress were significantly different between age (P < 0.05), gender (P < 0.05), and income groups (P < 0.001). Kidney cancer patients showed poorer psychologic health. The overall levels of anxiety, depression, and perceived stress symptoms were higher among the studied kidney cancer patients. Findings of the current study could improve both psychologic well-being of patients and health-related quality of life.

Identifying homogeneous healthcare use profiles and treatment sequences by combining sequence pattern mining with care trajectory clustering in kidney cancer patients on oral anticancer drugs: A case study

We evaluated the ability of a coupled pattern-mining and clustering method to identify homogeneous groups of subjects in terms of healthcare resource use, prognosis and treatment sequences, in renal cancer patients beginning oral anticancer treatment. Data were retrieved from the permanent sample of the French medico-administrative database. We applied the CP-SPAM algorithm for pattern mining to healthcare use sequences, followed by hierarchical clustering on principal components (HCPC). We identified 127 individuals with renal cancer with a first reimbursement of an oral anticancer drug between 2010 and 2017. Clustering identified three groups of subjects, and discrimination between these groups was good. These clusters differed significantly in terms of mortality at six and 12months, and medical follow-up profile (predominantly outpatient or inpatient care, biological monitoring, reimbursement of supportive care drugs). This case study highlights the potential utility of applying sequence-mining algorithms to a large range of healthcare reimbursement data, to identify groups of subjects homogeneous in terms of their care pathways and medical behaviors.

Prevalence and Trends of Drinking Water Disinfection Byproducts-Related Cancers in Addis Ababa, Ethiopia

Background:Disinfection byproducts (DBPs) from chlorinated drinking water have been linked to an increased risk of cancer in the bladder, stomach, colon, and rectum. No studies showed the independent trends and prevalence of these cancers in Ethiopia. Therefore, this study aimed to determine the prevalence and trends of disinfection byproducts-related cancers in Addis Ababa, Ethiopia.Methods:Data were collected from the Addis Ababa Cancer Registry. Spatial data sets were produced and classified into households receiving chlorinated surface water and less chlorinated groundwater. The Cochran-Armitage trend test was used to evaluate whether there was a disinfection byproducts-related cancers (DBRCs) trend among communities receiving chlorinated water. Negative binomial regression was used to analyze the incidence rate.Results:A total of 11, 438 cancer cases were registered between 2012 and 2016, and DBRCs accounted for approximately 17%. The majority of the total cancer cases were female; 7,706 (67%). The prevalence of DBRCs was found to be higher in communities supplied with chlorinated water. From 2012 to 2016, the trend of colon cancer increased (β = 10.3, P value = .034); however, esophageal cancer decreased (β = −6.5, P value = .018). Approximately 56% of colorectal cancer patients and 53% of stomach cancer patients are known to be using chlorinated surface water for drinking regularly. In addition, approximately 57.1% and 54% of kidney and bladder cancer patients, respectively, used chlorinated surface water.Conclusion:The prevalence of DBRCs in this study was found to be high. The colon cancer trend increased substantially from 2012 to 2016. The prevalence of DBRCs was higher in communities supplied with chlorinated surface water. Similarly, the prevalence of DBRCs was higher among males than females. Further study is required to validate the association between DBRCs and water chlorination.

The method of extracorporeal resection of the kidney in conditions of pharmaco-cold ischemia in kidney cancer with orthotopic renal replantation

BACKGROUND: Increasing the effectiveness of the treatment of patients with kidney cancer is one of the main problems of oncourology. In its solution, great importance is attached to the development of new surgical technologies.&#x0D; AIM: The aim of the study to evaluate the results of extracorporeal kidney resection in conditions of pharmaco-cold ischemia with orthotopic renal replantation in kidney cancer patients. Our study is aimed at assessing the results of extracorporeal resection of the kidney under pharmaco-cold ischemia with orthotopic replantation of renal vessels in patients with kidney cancer.&#x0D; MATERIALS AND METHODS: 44 patients [of them, 70.5% (n = 31) men and 29.5% (n = 13) women] with kidney cancer were recruited in a study. All patients were treated between 2012 and 2021. The mean age of patients was 55.92 12.6 years. The stage was determined using the TNM system: pT1a-3bN0M0-1 G1-3. 75% (n = 33) of patients had stage pT1a1b; 11.4% (n = 5) pT2a2b, one patient was present with multiple lesions; 13.6% (n = 6) pT3a3b, one patient had up to 15 lesions in a single kidney. Two previously operated patients had cancer of a single kidney with intraluminal invasion. The mean R.E.N.A.L nephrometric score was 10.32 1.34.&#x0D; RESULTS: The duration of the surgery was 402.07 83.21 minutes. The duration of cold ischemia was 149.9 53.1 minutes. Blood loss 751.1 633.6 ml. Renal vascular replacement was performed in 13 patients. Postoperative complications II degree according to Clavien Dindo were detected in 36.6% (16) of patients. There was only one lethal outcome due to mesenteric thrombosis at day 4. Disease progressed in 6.8% (n = 3) of cases. The GFR level before surgery was on average 72.3 16.8 ml / (min 1.73 m2), in the early postoperative period 58.7 28.3 ml / (min 1.73 m2), 1 year after surgery 69.4 26.2 ml / (min 1.73 m2). One year after surgery it was 69.4 26.2 mol/l. The follow-up period ranged from 8 to 86 months (on average 58.7 19.1 months).&#x0D; CONCLUSIONS: This technique is effective in patients with multiple foci, centrally located and large tumors, for hard-to-reach localizations, as well as in patients with the impossibility of intracorporeal pharmaco-cold ischemia, peculiarities of organ blood supply.

Examining the Relationship between Depression, Anxiety and Stress in Kidney Cancer Patients

Cancer of the kidney is one of the 10 most common cancers found globally. Overall, it is the fourth most common cancer in men and the eighth most common cancer in women. Many kidney cancer patients experience psychologic problems and reactions. The present study examined relationship between anxiety, depression, and perceived stress symptoms in kidney cancer patients. Cross-sectional data were obtained from the patients diagnosed with kidney cancer. All participants completed sociodemographic form, Hospital Anxiety and Depression form, and Perceived Stress Scale. Statistical analysis was exercised using the Student’s t-test, Chi-squared test (χ2), Fischer’s exact test, ANOVA, Mann–Whitney U test, and Kruskal–Wallis one-way variance analysis. A total of 250 patients participated in the study. The mean age was 57.4 years (SD 6.4, range = 25–76 years). The majority of patients were males (73%) and married (218). Anxiety symptoms were determined in 91.2% patients, depression symptoms in 87.2% patients, and perceived stress symptoms in 93.6% patients. The mean scores of Hospital Depression and Anxiety Scale (HADS)-Anxiety, HADS-Depression, and HADS-Perceived Stress were significantly different between age (P < 0.05), gender (P < 0.05), and income groups (P < 0.001). Kidney cancer patients showed poorer psychologic health. The overall levels of anxiety, depression, and perceived stress symptoms were higher among the studied kidney cancer patients. Findings of the current study could improve both psychologic well-being of patients and health-related quality of life.

A Population-Based Study of Cardiovascular Disease Mortality in Italian Cancer Patients.

Simple SummaryResearch suggests that lengthening the prognosis in cancer patients (which is certainly a positive thing) requires greater attention to be paid to the onset of other pathologies. The increase in cardiovascular mortality in cancer patients (due to both exposure to risk factors and the side effects of cytotoxic drugs) requires greater collaboration between oncologists and cardiologists, and the integration of shared follow-up paths. Particular attention to the follow-up of cancer patients can reduce this risk: in the present study, patients presented an excessive risk of cardiovascular mortality only in the first two years from cancer diagnosis.The present research describes 25 years of cardiovascular mortality in a cohort of patients in Northern Italy. The study included patients with malignant cancer enrolled in the period of 1996–2019, and describes cardiovascular and cancer mortality in relation to sex, age, year of diagnosis, months of survivorship, tumor site, and standardized mortality ratio (SMR). Out of 67,173 patients, 38,272 deaths (57.7%) were recorded: 4466 from cardiovascular disease (CVD) (6.6%), and 28,579 (42.6%) from cancer. The proportion of CVD death increased from 4.5% in the first two years after diagnosis, to 7.3% after more than 10 years, while the proportion of deaths from cancer decreased from 70.5% to 9.4%. The CVD SMR comparing cancer patients with the general population was 0.87 (95% CI: 0.82–0.92) in 1996–1999, rising to 0.95 (95% CI: 0.84–1.08) in 2015–2019, without differences in terms of sex or age. The risk of dying from CVD was higher compared with the general population (SMR 1.31; 95% CI: 1.24–1.39) only in the first two years after diagnosis. The trend over time underscored that CVD deaths increased in patients with breast, bladder, prostate, and colorectal cancers, and, in the more recent period, for kidney cancer and melanoma patients. Our data confirmed that cardiovascular mortality is an important issue in the modern management of cancer patients, suggesting the need for an extensive interdisciplinary approach.

Emotional state and cancer-related self-efficacy as affecting resilience and quality of life in kidney cancer patients: a cross-sectional study.

To assess the relationship between resilience and quality of life (QOL) of kidney cancer patients, including influencing factors. Based on a cross-sectional study design, participants (N = 103) were recruited from patients who were admitted to the urology clinic of a medical center in Taiwan between April 2020 and January 2021. Data collection was accomplished via a questionnaire. The study variables included demographic information, disease attributes, happiness level, depression, cancer-related self-efficacy, resilience, and QOL. One-way analysis of variance, Pearson correlation coefficients, independent-sample t-tests, hierarchical regression, and process analysis were the statistical methods used to analyze the data. Kidney cancer patients who were less depressed exhibited better cancer-related self-efficacy and have better resilience. In non-depressed individuals, higher levels of happiness and better resilience resulted in better QOL. Resilience is a mediator that affects the relationship between depression and QOL. Patients with better emotional state experience better resilience and QOL. Patients' better cancer-related self-efficacy is related to better resilience while better resilience is associated with better QOL. Clinical care providers need to evaluate and improve cancer-related self-efficacy, emotional state, and resilience of kidney cancer patients, which will improve their resilience and QOL.

Hereditary kidney cancer - easily clarified and diagnosed with ToSCaNA

In recent years great improvements in the diagnosis and differentiation of hereditary syndroms with predisposition for kidney cancer have been achieved. It has been assumed that 5-8% of all kidney cancer have a hereditary origin. In reality, this number will probably be much higher as many genetic aspects of kidney cancer are still not entirely known. Hereditary kidney cancer usually shows two characteristic properties: While the median age of diagnosis of sporadic renal cell carcinoma is 64 years, patients with a hereditary tumor predisposition are about 20 years younger at the time of diagnosis. Additionally, their tumors often occur multifocal/bilateral. Therefore, a special management with extended diagnostics is necessary for these young kidney cancer patients. In literature many reports on hereditary syndromes with kidney cancer predisposition exist. Though, these papers usually put their focus on single syndromes rather than on the aspects of kidney cancer. The goal of this article is to present the practicing urologist with a compact overview of the most important hereditary syndromes with kidney cancer predisposition and by this improve the primary diagnostic and treatment of renal cancer patients and their relatives. We conducted a literature search on the five most important hereditary syndromes with kidney cancer association and summarized the results in a chart. Additionally, we formed the acronym ToSCaNA combining the most important extrarenal manifestations of the syndromes. Based on this data, a diagnostic workflow and treatment path was established. All in all, hereditary kidney cancer is a rare entity, which nonetheless could present as a significant number in high-volume centers. For doctors who scarcely get in contact with these types of tumors, the acronym and workflow could pose a valuable asset for their clinical diagnostic portfolio. An early identification and diagnostic work-up of affected patients and their relatives is crucial for appropriate treatment and surveillance and allows the identification/treatment of additionally affected relatives. In patients with young age of onset and multifocal/bilateral occurrence of kidney cancer, hereditary syndromes should always be considered. The initial suspicion of a hereditary genesis of the cancer can be further evaluated by the acronym ToSCaNA and the presented workflow.

Plasma lipidomic profiles of kidney, breast and prostate cancer patients differ from healthy controls

Early detection of cancer is one of the unmet needs in clinical medicine. Peripheral blood analysis is a preferred method for efficient population screening, because blood collection is well embedded in clinical practice and minimally invasive for patients. Lipids are important biomolecules, and variations in lipid concentrations can reflect pathological disorders. Lipidomic profiling of human plasma by the coupling of ultrahigh-performance supercritical fluid chromatography and mass spectrometry is investigated with the aim to distinguish patients with breast, kidney, and prostate cancers from healthy controls. The mean sensitivity, specificity, and accuracy of the lipid profiling approach were 85%, 95%, and 92% for kidney cancer; 91%, 97%, and 94% for breast cancer; and 87%, 95%, and 92% for prostate cancer. No association of statistical models with tumor stage is observed. The statistically most significant lipid species for the differentiation of cancer types studied are CE 16:0, Cer 42:1, LPC 18:2, PC 36:2, PC 36:3, SM 32:1, and SM 41:1 These seven lipids represent a potential biomarker panel for kidney, breast, and prostate cancer screening, but a further verification step in a prospective study has to be performed to verify clinical utility.

Association of Health-Related Quality of Life with Overall Survival in Older Americans with Kidney Cancer: A Population-Based Cohort Study.

Background: Our purpose was to evaluate associations between health-related quality of life (HRQoL) and overall survival (OS) in a population-based sample of kidney cancer (KC) patients in the US. Methods: We analyzed a longitudinal cohort (n = 188) using the Surveillance, Epidemiology, and End Results (SEER) database linked with the Medicare Health Outcomes Survey (MHOS; 1998–2014). We included KC patients aged ≥65 years, with a completed MHOS during baseline (pre-diagnosis) and another during follow-up (post-diagnosis). We reported HRQoL as physical component summary (PCS) and mental component summary (MCS) scores and OS as number of months from diagnosis to death/end-of-follow-up. Findings were reported as adjusted hazard ratios (aHRs (95% CI)) from Cox Proportional Hazard models. Results: The aHRs associated with a 3-point lower average (baseline and follow-up) or a 3-point within-patient decline (change) in HRQoL with OS were: (a) baseline: PCS (1.08 (1.01–1.16)) and MCS (1.09 (1.01–1.18)); (b) follow-up: PCS (1.21 (1.12–1.31)) and MCS (1.11 (1.04–1.19)); and (c) change: PCS (1.10 (1.02–1.18)) and MCS (1.02 (0.95–1.10)). Conclusions: Reduced HRQoL was associated with worse OS and this association was strongest for post-diagnosis PCS, followed by change in PCS and pre-diagnosis PCS. Findings highlight the prognostic value of HRQoL on OS, emphasize the importance of monitoring PCS in evaluating KC prognosis, and contribute additional evidence to support the implementation of patient-reported outcomes in clinical settings.

The Impact of Metformin Use with Survival Outcomes in Urologic Cancers: A Systematic Review and Meta-Analysis.

Background Conflicting results exist between the potential protective effects of metformin and the prognosis of urologic cancers. This meta-analysis summarized the effects of metformin exposure on the recurrence, progression, cancer-specific survival (CSS), and overall survival (OS) of the three main urologic cancers (kidney cancer, bladder cancer, and prostate cancer). Methods We systematically searched PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases (January 2010 to December 2019), which identified studies regarding metformin users and nonusers with urologic cancers and extracted patient data. A random effect model or fixed effect model was used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs). Results Among the 1883 confirmed studies, 27 eligible studies were identified, including 123,212 participants. In prostate cancer, patients using metformin have significant benefits for recurrence (HR = 0.74; 95% CI: 0.61-0.90; P = 0.007; I2 = 56%), CSS (HR = 0.74; 95% CI: 0.61-0.91; P = 0.002; I2 = 79%), and OS (HR = 0.76; 95% CI: 0.65-0.90; P < 0.001; I2 = 86%). Moreover, further subgroup analysis showed that the beneficial effects of metformin may be more significant for patients receiving radical radiotherapy. For kidney cancer, metformin was beneficial for progression (HR = 0.80; 95% CI: 0.65-0.98; P = 0.14; I2 = 46%). Analysis revealed that the effect of metformin on the overall survival of kidney cancer patients may be related to nationality (American: HR = 0.76; 95% CI: 0.59-0.98; P = 0.88; I2 = 0%). For bladder cancer, no obvious benefits of metformin use were identified. However, subgroup analysis indicated that metformin may improve the recurrence of bladder cancer, but this improvement was only found in patients with a median follow-up time of more than 4 years (HR = 0.43; 95% CI: 0.28-0.67; P = 0.61; I2 = 0%).

The RNA N6-Methyladenosine Methyltransferase METTL3 Promotes the Progression of Kidney Cancer via N6-Methyladenosine-Dependent Translational Enhancement of ABCD1.

The role of N6-methyladenosine (m6A)-modifying proteins in cancer progression depends on the cell type and mRNA affected. However, the biological role and underlying mechanism of m6A in kidney cancer is limited. Here, we discovered the variability in m6A methyltransferase METTL3 expression was significantly increased in clear cell renal cell carcinoma (ccRCC) the most common subtype of renal cell carcinoma (RCC), and high METTL3 expression predicts poor prognosis in ccRCC patients using a dataset from The Cancer Genome Atlas (TCGA). Importantly, knockdown of METTL3 in ccRCC cell line impaired both cell migration capacity and tumor spheroid formation in soft fibrin gel, a mechanical method for selecting stem-cell-like tumorigenic cells. Consistently, overexpression of METTL3 but not methyltransferase activity mutant METTL3 can promote cell migration, spheroid formation in cell line and tumor growth in xenograft model. Transcriptional profiling of m6A in ccRCC tissues identified the aberrant m6A transcripts were enriched in cancer-related pathways. Further m6A-sequencing of METTL3 knockdown cells and functional studies confirmed that translation of ABCD1, an ATP-binding cassette (ABC) transporter of fatty acids, was inhibited by METTL3 in m6A-dependent manner. Moreover, knockdown of ABCD1 in ccRCC cells decreased cancer cell migration and spheroid formation, and upregulation of ABCD1 acts as an adverse prognosis factor of kidney cancer patients. In summary, our study identifies that METTL3 promotes ccRCC progression through m6A modification-mediated translation of ABCD1, providing an epitranscriptional insight into the molecular mechanism in kidney cancer.

Survival of bladder or renal cancer in patients with CHEK2 mutations.

PurposeThe purpose of this study was to compare the clinical characteristics and the survival of CHEK2 mutation positive and CHEK2 mutation negative patients diagnosed with bladder or kidney cancer.Materials and methods1016 patients with bladder and 402 cases with kidney cancer and 8302 controls were genotyped for four CHEK2 variants: 1100delC, del5395, IVS2+1G>A and I157T. Predictors of survival were determined among CHEK2 pathogenic variant carriers using the Cox proportional hazards model. The median follow-up was 17.5 years. Covariates included age (≤60; >61 years), sex (female; male), clinical characteristics (stage: TNM, grade, histopathological type), smoking status (non-smoking; smoking) and cancer family history (negative; positive).ResultsWe found no impact of CHEK2 mutations on bladder or kidney cancer survival. However, we observed a possible increased survival in the subgroup of patients with stage T1 bladder cancer with CHEK2 mutations but this did not meet statistical significance (HR = 0.14; 95% CI 0.02–1.04; p = 0.055). Moreover, we observed that the missense mutations were more frequent in the low grade invasive bladder cancer patient group (OR = 7.9; 95% CI 1.50–42.1; p = 0.04) and in patients with bladder cancer with stage Ta (OR = 2.4; 95% CI 1.30–4.55; p = 0.006). The different results where missense mutations occurs less often we observed among patients with high grade invasive bladder cancer (OR = 0.12; 95% CI 0.02–0.66; p = 0.04) and those with stage T1 disease (OR = 0.2; 95% CI 0.07–0.76; p = 0.01). Our investigations revealed that any mutation in CHEK2 occurs more often among patients with stage Ta bladder cancer (OR = 2.0; 95% CI 1.19–3.47; p = 0.01) and less often in patients with stage T1 disease (OR = 0.31; 95% CI 0.12–0.78; p = 0.01). In the kidney cancer patients, truncating mutations were present more often in the group with clear cell carcinoma GII (OR = 8.0; 95% CI 0.95–67.7; p = 0.05). The 10-year survival for all CHEK2 mutation carriers with bladder cancer was 33% and for non-carriers 11% (p = 0.15). The 10-year survival for CHEK2 mutation carriers with kidney cancer 34% and for non-carriers 20% (p = 0.5).ConclusionCHEK2 mutations were not associated with any change in bladder or kidney cancer survival regardless of their age, sex, smoking status and family history. We observed a potentially protective effect of CHEK2 mutations on survival for patients with stage T1 bladder cancer. CHEK2 missense mutations were more common among patients with low grade invasive bladder cancer and in patients with stage Ta diease. The frequencies of the I157T CHEK2 pathogenic variant were less in patients with high grade invasive bladder cancer and those with stage T1 disease. Among patients with bladder cancer with stage Ta disease, the OR for any mutation in CHEK2 was 2.0 but for those with stage T1 disease, the OR was 0.3. We observed truncating CHEK2 mutations were associated with kidney cancer patients with GII clear cell carcinoma.

PD45-04 OUTCOMES OF GENITOURINARY MALIGNANCY IN SOLID ORGAN TRANSPLANT RECIPIENTS

You have accessJournal of UrologyRenal Transplantation & Vascular Surgery II (PD45)1 Sep 2021PD45-04 OUTCOMES OF GENITOURINARY MALIGNANCY IN SOLID ORGAN TRANSPLANT RECIPIENTS Song Jiang, Brent Cleveland, and Christopher Warlick Song JiangSong Jiang More articles by this author , Brent ClevelandBrent Cleveland More articles by this author , and Christopher WarlickChristopher Warlick More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002059.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The management of genitourinary (GU) malignancy in transplant recipients is challenging and remains controversial, often based on historical practices that fail to take into account recent progress in both genitourinary cancer diagnosis and management, as well as immunosuppression protocols used by modern transplant teams. Data regarding rates and outcomes of GU malignancy in the solid organ transplant (SOT) population is lacking, and studies that exist have small numbers of patients. The purpose of this study is to examine the incidence, disease characteristics, and clinical course of bladder and kidney cancer diagnosed in a large solid organ transplant cohort. METHODS: The University of Minnesota SOT database, curated based on UNOS data collected from 1984–2019, was queried for SOT recipients who subsequently developed bladder cancer and renal neoplasm. A retrospective chart review of available electronic medical records was performed based on the results of this query to obtain patient characteristics, pathology, treatment, and outcomes. RESULTS: In our cohort of SOT recipients, 42 patients were subsequently diagnosed with bladder cancer. High grade and advanced disease (T2 or greater) were present in 27 (64.3%) and 16 (38.1%) of patients, respectively. Recurrences occurred in 17 patients with 6 (35%) of these being progression in disease. Bladder cancer-related deaths occurred in 8 patients (19.1%). The mean overall survival after initial diagnosis was 2.8 (±3.3) years. 111 SOT patients developed a renal neoplasm in the native kidney, whereas 33 developed a neoplasm in a graft kidney. The large majority of renal masses were localized and treated with radical nephrectomy. 2 patients developed progression of disease after radical surgery with evidence of metastasis, while 3 patients had evidence of metastasis on presentation. CONCLUSIONS: Previously, we have described cumulative incidence of genitourinary malignancy in a large cohort of renal transplant recipients at the University of Minnesota. Herein, we present a study of the broader solid organ transplant population and present disease characteristics and outcomes of bladder and kidney cancer patients, which revealed that those diagnosed with de novo bladder malignancy after their transplant had increased rates of high grade and advanced disease (T2 or greater) at initial diagnosis compared to commonly cited rates for the general population, whereas in the case of renal cell cancer we noted an increased rate of diagnosis, but rates of disease progression and metastasis largely in line with the general population. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e743-e743 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Song Jiang More articles by this author Brent Cleveland More articles by this author Christopher Warlick More articles by this author Expand All Advertisement Loading ...

Review of Plasma Lipidomic Profiles of Kidney, Breast, and Prostate Cancer Patients Differ from Healthy Controls

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