Kidney Cancer Patients Research Articles

Non-neoplastic Kidney Diseases in Adult Tumor Nephrectomy and Nephroureterectomy Specimens in a Southeast Asian Tertiary Medical Center

OBJECTIVE: Non-neoplastic kidney diseases are concurrently present in up to 15% of patients with renal and ureteral tumors, which have been most studied in the United States. This study was conducted to determine the prevalence and spectrum of renal parenchymal diseases in similar patients from a Southeast Asian academic institution.METHODS: We searched the database of the Department of Anatomical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University (2012–2022) and found 194 adult nephrectomy and nephroureterectomy specimens with renal, renal pelvis, and ureteral tumors. Additional stains included periodic acid-Schiff, methenamine silver, and Masson trichrome. Direct immunofluorescence microscopy was performed on the paraffin tissue sections for immunoglobulin (Ig) G, IgA, IgM, and kappa and lambda light chains. Clinical information, including age, gender, and co-morbidities, was obtained from the electronic medical records.RESULTS: Analysis of the 194 cases demonstrated the average age was 61 years (range: 17-89 years), with 126 males (65%) and 68 females (35%). After re-examination of the non-neoplastic renal parenchyma, 14 cases (7%) had diffused and/or nodular mesangial sclerosis. Diabetic nephropathy (12 cases) and idiopathic nodular glomerulosclerosis (2 cases) were diagnosed and associated with either stage 1 or 2 genitourinary cancers. Another case was diagnosed with atheroembolic renal disease. In all cases, the concurrent renal diseases were not identified during the initial evaluation.CONCLUSION: Examination of the non-neoplastic renal parenchyma is important to identify non-neoplastic kidney diseases, such as diabetic nephropathy, so early treatment may result in improved clinical outcomes for kidney and urothelial cancer patients.

Impact of Palliative Care Utilization among Kidney Cancer Patients in US Hospitals: A National-Scale Analysis

The objective of this study was to examine the characteristics and utilization patterns of palliative care among the kidney cancer patients using a large-scale representative population-based sample. We retrospectively analyzed National Inpatient Sample hospitalization data from January 2020 to December 2020 to explore disparities in delivering palliative care to deceased kidney cancer patients and assess its impact on healthcare usage, focusing on hospital costs and length of stay (LoS). We used ICD-10 CM codes (International Classification of Diseases-classifying diagnoses and reasons for visits in all healthcare settings) to categorize the study population. We conducted univariable and multivariable linear and logistic regression analyses to calculate coefficients and odds ratios, considering relevant variables and addressing potential confounding factors. We studied 1437 deceased kidney cancer patients, with 53.9% receiving palliative care. Those receiving palliative care had lower total costs ($99,804 vs. $1,34,731) and a shorter LoS (7.19 days vs. 7.66 days), compared to those who didn’t. No significant difference was discovered in LoS. Private insurance, higher income, and female patients were more likely to receive palliative care. Race, hospital teaching status, and hospital size showed no significant differences. This study revealed insights into palliative care use among deceased kidney cancer patients, with cost-saving benefits evident. Disparities showed that individuals with private insurance and higher income more likely accessed palliative care, and females received it more often than males. Physicians and policymakers must consider these findings for equitable resource allocation and improved access.

Downregulation of praja2 restrains endocytosis and boosts tyrosine kinase receptors in kidney cancer

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer in the adult population. Late diagnosis, resistance to therapeutics and recurrence of metastatic lesions account for the highest mortality rate among kidney cancer patients. Identifying novel biomarkers for early cancer detection and elucidating the mechanisms underlying ccRCC will provide clues to treat this aggressive malignant tumor. Here, we report that the ubiquitin ligase praja2 forms a complex with-and ubiquitylates the AP2 adapter complex, contributing to receptor endocytosis and clearance. In human RCC tissues and cells, downregulation of praja2 by oncogenic miRNAs (oncomiRs) and the proteasome markedly impairs endocytosis and clearance of the epidermal growth factor receptor (EGFR), and amplifies downstream mitogenic and proliferative signaling. Restoring praja2 levels in RCC cells downregulates EGFR, rewires cancer cell metabolism and ultimately inhibits tumor cell growth and metastasis. Accordingly, genetic ablation of praja2 in mice upregulates RTKs (i.e. EGFR and VEGFR) and induces epithelial and vascular alterations in the kidney tissue.In summary, our findings identify a regulatory loop between oncomiRs and the ubiquitin proteasome system that finely controls RTKs endocytosis and clearance, positively impacting mitogenic signaling and kidney cancer growth.

A dynamic visualization clinical tool constructed and validated based on the SEER database for screening the optimal surgical candidates for bone metastasis in primary kidney cancer

The implementation of primary tumor resection (PTR) in the treatment of kidney cancer patients (KC) with bone metastases (BM) has been controversial. This study aims to construct the first tool that can accurately predict the likelihood of PTR benefit in KC patients with BM (KCBM) and select the optimal surgical candidates. This study acquired data on all patients diagnosed with KCBM during 2010–2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was utilized to achieve balanced matching of PTR and non-PTR groups to eliminate selection bias and confounding factors. The median overall survival (OS) of the non-PTR group was used as the threshold to categorize the PTR group into PTR-beneficial and PTR-Nonbeneficial subgroups. Kaplan–Meier (K–M) survival analysis was used for comparison of survival differences and median OS between groups. Risk factors associated with PTR-beneficial were identified using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC), area under the curve (AUC), calibration curves, and decision curve analysis (DCA) were used to validate the predictive performance and clinical utility of the nomogram. Ultimately, 1963 KCBM patients meeting screening criteria were recruited. Of these, 962 patients received PTR and the remaining 1061 patients did not receive PTR. After 1:1 PSM, there were 308 patients in both PTR and non-PTR groups. The K–M survival analysis results showed noteworthy survival disparities between PTR and non-PTR groups, both before and after PSM (p < 0.001). In the logistic regression results of the PTR group, histological type, T/N stage and lung metastasis were shown to be independent risk factors associated with PTR-beneficial. The web-based nomogram allows clinicians to enter risk variables directly and quickly obtain PTR beneficial probabilities. The validation results showed the excellent predictive performance and clinical utility of the nomograms for accurate screening of optimal surgical candidates for KCBM. This study constructed an easy-to-use nomogram based on conventional clinicopathologic variables to accurately select the optimal surgical candidates for KCBM patients.

Secondary primary malignancies among patients with GU cancer.

98 Background: The risk of secondary primary malignancies (SPM) among the survivors of GU cancer is not well-established. In this study, we attempt to describe the patterns of SPMs in patients diagnosed with GU cancers. Methods: The Surveillance, Epidemiology, and End Results (SEER) database (SEER*Stat 8.4.2) was searched to obtain data on the incidence of SPM in adult patients (age &gt;18 years) diagnosed with GU cancers, including prostate, renal, and bladder cancer. Standardized incidence ratios (SIRs) with a 95% confidence interval (CI) were calculated. SIR was defined as the observed SPMS from each category divided by the expected number of SPMs in the age-matched US population for the same period. The data was further stratified by age (&lt;50y, 50-70y, &gt;70y), race (White, Black, Asian/Pacific Islander), ethnicity (Hispanic, non-Hispanic), chemotherapy, and radiotherapy exposure. Results: A total of 1,041,217 patients were included in this analysis. In patients diagnosed with GU cancer, the incidence of overall SPM was 11%. Particularly, patients with GU cancers were observed to have a high incidence of Endocrine system SPM (1.52; 1.45-1.59), and urinary system SPM (1.51; 1.49-1.53) These results were consistent by different sociodemographic groups. In patients diagnosed with prostate cancer, the incidence of thyroid SPM was increased (1.31; 1.23-1.39). Particularly, prostate cancer patients treated with radiation therapy had increased incidence rates of SPM in the peritoneum, omentum and mesentery (1.57; 0.79-2.81) and urinary bladder (1.36;1.32-1.40) was higher as compared to those with no exposure to radiation therapy (1.11;1.08-1.13 and 1.03;1-1.06 respectively). Bladder cancer patients had an overall increased incidence of SPM in the esophagus (1.21; 1.08-1.35), lung, bronchus, trachea, and other respiratory organs (1.97;1.92-2.01), prostate (3.50;3.4-3.6) and kidney (1.86;1.76-1.97). A higher incidence of renal pelvis, ureter and other urinary organ SPM (11.08;10.48-11.07) was also notable in this population. Similarly, kidney cancer patients had a higher incidence of the endocrine system (3.00;2.74-3.27), prostate (1.24;1.2-1.29) and bladder 1.78;1.68-1.79 SPMs. Conclusions: This population-based study shows an increased risk of SPM development in GU cancer survivors compared to the general population. Clinicians should keep a high index of suspicion for SPMs and initiate appropriate workups at early warning signs.

Telemedicine in urologic oncology care: Will telemedicine exacerbate disparities?

IntroductionDisparities in prostate, bladder, and kidney cancer outcomes are associated with access to care. Telemedicine can improve access but may be underutilized by certain patient populations. Our objective was to determine if the patient populations who suffer worse oncologic outcomes are the same as those who are less likely to use telemedicine. MethodsUsing an institutional database, we identified all prostate, bladder and kidney cancer encounters from March 14, 2020 to October 31, 2021 (n = 15,623; n = 4, 14; n = 3,830). Telemedicine was used in 13%, 8%, and 12% of these encounters, respectively. We performed random effects modeling analysis to examine patient and provider characteristics associated with telemedicine use. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were reported as measures of association. ResultsAmong prostate, bladder, and kidney cancer patients, Black patients had lower odds of a telemedicine encounter (OR 0.51, 95% CI 0.37–0.69; OR 0.22, 95% CI 0.07–0.70; OR 0.46, 95% CI 0.24–0.86), and patients residing in small and isolated small rural towns areas had higher odds of a telemedicine encounter (OR 1.44, 95% CI 1.09–1.91; OR 2.12, 95% CI 1.14–3.94; OR 1.89, 95% CI 1.12–3.19). Compared to providers in practice ≤5 years, providers in practice for 6 to 15 years had significantly higher odds of a telemedicine encounter for prostate and bladder cancer patients (OR 4.10, 95% CI 1.4511.58; OR 3.42, 95% CI 1.09–10.77). ConclusionThe lower rates of telemedicine use among Black patients could exacerbate pre-existing disparities in prostate, bladder, and kidney cancer outcomes.

Racial disparities in GU cancer metastasis: A comprehensive analysis from 2010-2018.

30 Background: Patterns of metastatic spread vary between bladder, kidney, and prostate metastasis. Of these cancers, kidney cancer often spreads to the brain, while prostate cancer is most likely to spread to bone, for example. Sites of metastasis can influence prognosis and in some instances may even direct therapy. The knowledge gap on racial disparities in metastatic patterns merits further investigation. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified bladder, kidney, and prostate cancer patients (2010-2018) in White (W) and Black (B) races. Data on metastasis to the lungs, liver, bones, and brain at diagnosis were extracted. The relative risk (RR) was calculated to compare the metastatic patterns between Black and White patients. P-value, and confidence interval were computed using SPSS 28.0. Results: 3.95% of Black and 1.65% of White patients had metastasis at diagnosis. Black patients had metastasis prevalence of 3.2% lung, 1.8% liver, 4.4% bone, and 0.3% brain. Comparatively, White patients had 1.3%, 0.8%, 3.2%, and 0.3% respectively. For bladder cancer, Black patients had a 60% higher risk for bone and lung metastasis and double the risk for liver metastasis compared to White patients. In kidney cancer, Black patients had a 90% higher brain metastasis risk but 20% lower for bone and lung than White patients. For prostate, Black patients had comparatively heightened risks of bone, lung, and liver metastases by 10%, 20%, and 30%, respectively. Conclusions: Racial disparities are evident in GU cancer metastatic patterns at time of diagnosis. Black patients especially have higher liver metastasis, often associated with poor prognosis. Further studies are vital to unravel biological, socioeconomic, and other contributing factors. [Table: see text]

Total polyphenols of Cydonia oblonga inhibited proliferation and migration of renal cancer cells by PI3K/Akt/mTOR pathway

The mechanism of total polyphenols of Cydonia oblonga Miller(TPCOM) against kidney cancer was elucidated through a combination of network pharmacology, bioinformatics, and experimental verification. The active polyphenolic compounds from C. oblonga were screened by network pharmacological techniques and kidney cancer-related targets were collected through the database. The differential gene expression analysis was performed on RNA sequencing data from tumor tissue and normal tissue of kidney cancer patients obtained from the Gene Expression Omnibus(GEO) database. The results of network pharmacology predictions and differential gene expression analysis were used to identify the core genes targeted by TPCOM in kidney cancer. Survival analysis was conducted to identify key targets that could impact patient survival, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) enrichment analyses. Cell proliferation and activity experiments(cell counting kit-8) were conducted using TPCOM at concentrations ranging from 20 to 640 μg·mL~(-1) on 786-O and Renca cells. Additionally, TPCOM at concentrations of 40, 80, and 160 μg·mL~(-1) was applied to kidney cancer cells to assess its effect on cell migration and its regulation of protein expression levels related to the protein kinase B(Akt), mammalian target of rapamycin(mTOR), and phosphoinositide 3-kinase(PI3K) signaling pathways. Network pharmacology predicted eight active polyphenolic compounds from C. oblonga. Survival analysis revealed 15 significantly differentially expressed genes in kidney cancer that were affected by TPCOM and had a significant impact on patient survival. KEGG and GO analysis results indicated that these 15 targets were primarily associated with the PI3K/Akt signaling pathway, cell migration, and proliferation. The results showed that TPCOM could inhibit the proliferation of 786-O and Renca cells, with IC_(50) values of 121.4 and 137.9 μg·mL~(-1), respectively. TPCOM was also found to inhibit the migration of these cells and suppress the PI3K/Akt/mTOR signaling pathway. TPCOM may exert its anti-kidney cancer effects by inhibiting the activation of the PI3K/Akt/mTOR signaling pathway, thereby restraining the proliferation and migration of kidney cancer cells. This study provides a foundation for the research on the anti-tumor effects of natural product C. oblonga, particularly in Xinjiang, and holds significance for further promoting its development and utilization.

The global, regional, and national burden and quality of care index of kidney cancer; a global burden of disease systematic analysis 1990-2019.

Kidney cancer (KC) is a prevalent cancer worldwide. The incidence and mortality rates of KC have risen in recent decades. The quality of care provided to KC patients is a concern for public health. Considering the importance of KC, in this study, we aim to assess the burden of the disease, gender and age disparities globally, regionally, and nationally to evaluate the quality and inequities of KC care. The 2019 Global Burden of Disease study provides data on the burden of the KC. The secondary indices, including mortality-to-incidence ratio, disability-adjusted life years -to-prevalence ratio, prevalence-to-incidence ratio, and years of life lost-to-years lived with disability ratio, were utilized. These four newly merged indices were converted to the quality-of-care index (QCI) as a summary measure using principal component analysis. QCI ranged between 0 and 100, and higher amounts of QCI indicate higher quality of care. Gender disparity ratio was calculated by dividing QCI for females by males to show gender inequity. The global age-standardized incidence and mortality rates of KC increased by 29.1% (95% uncertainty interval 18.7-40.7) and 11.6% (4.6-20.0) between 1990 and 2019, respectively. Globally, the QCI score for KC increased by 14.6% during 30 years, from 71.3 to 81.6. From 1990 to 2019, the QCI score has increased in all socio-demographic index (SDI) quintiles. By 2019, the highest QCI score was in regions with a high SDI (93.0), and the lowest was in low SDI quintiles (38.2). Based on the World Health Organization regions, the QCI score was highest in the region of America, with Canada having the highest score (99.6) and the lowest in the African Region, where the Central African Republic scored the lowest (17.2). In 1990, the gender disparity ratio was 0.98, and in 2019, it was 0.97 showing an almost similar QCI score for females and males. Although the quality of care for KC has improved from 1990 to 2019, there is a significant gap between nations and different socioeconomic levels. This study provides clinicians and health authorities with a global perspective on the quality of care for KC and identifies the existing disparities.

Identification and Validation of Cytotoxicity-Related Features to Predict Prognostic and Immunotherapy Response in Patients with Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a renal cortical malignancy with a complex pathogenesis. Identifying ideal biomarkers to establish more accurate promising prognostic models is crucial for the survival of kidney cancer patients. Seurat R package was used for single-cell RNA-sequencing (scRNA-seq) data filtering, dimensionality reduction, clustering, and differentially expressed genes analysis. Gene coexpression network analysis (WGCNA) was performed to identify the cytotoxicity-related module. The independent cytotoxicity-related risk model was established by the survival R package, and Kaplan-Meier (KM) survival analysis and timeROC with area under the curve (AUC) were employed to confirm the prognosis and effectiveness of the risk model. The risk and prognosis in patients suffering from ccRCC were predicted by establishing a nomogram. A comparison of the level of immune infiltration in different risk groups and subtypes using the CIBERSORT, MCP-counter, and TIMER methods, as well as assessment of drug sensitivity to conventional chemotherapeutic agents in risk groups using the pRRophetic package, was made. Eleven ccRCC subpopulations were identified by single-cell sequencing data from the GSE224630 dataset. The identified cytotoxicity-related T-cell cluster and module genes defined three cytotoxicity-related molecular subtypes. Six key genes (SOWAHB, SLC16A12, IL20RB, SLC12A8, PLG, and HHLA2) affecting prognosis risk genes were selected for developing a risk model. A nomogram containing the RiskScore and stage revealed that the RiskScore contributed the most and exhibited excellent predicted performance for prognosis in the calibration plots and decision curve analysis (DCA). Notably, high-risk patients with ccRCC demonstrate a poorer prognosis with higher immune infiltration characteristics and TIDE scores, whereas low-risk patients are more likely to benefit from immunotherapy. A ccRCC survival prognostic model was produced based on the cytotoxicity-related signature, which had important clinical significance and may provide guidance for ccRCC treatment.

The influence of sex hormones on renal cell carcinoma.

Kidney cancer is a common malignancy that constitutes around 5% of all cancer cases. Males are twice as likely to acquire renal cell carcinoma (RCC) compared to females and experience a higher rate of mortality. These disparities indicate that sex hormone (SH)-dependent pathways may have an impact on the aetiology and pathophysiology of RCC. Examination of SH involvement in conventional signalling pathways, as well as genetics and genomics, especially the involvement of ribonucleic acid, reveal further insights into sex-related differences. An understanding of SHs and their influence on kidney cancer is essential to offer patients individualized medicine that would better meet their needs in terms of prevention, diagnosis and treatment. This review presents the understanding of sex-related differences in the clinical manifestation of kidney cancer patients and the underlying biological processes.

Mitochondrial DNA Variants at Low-Level Heteroplasmy and Decreased Copy Numbers in Chronic Kidney Disease (CKD) Tissues with Kidney Cancer.

The human mitochondrial genome (mtDNA) is a circular DNA molecule with a length of 16.6 kb, which contains a total of 37 genes. Somatic mtDNA mutations accumulate with age and environmental exposure, and some types of mtDNA variants may play a role in carcinogenesis. Recent studies observed mtDNA variants not only in kidney tumors but also in adjacent kidney tissues, and mtDNA dysfunction results in kidney injury, including chronic kidney disease (CKD). To investigate whether a relationship exists between heteroplasmic mtDNA variants and kidney function, we performed ultra-deep sequencing (30,000×) based on long-range PCR of DNA from 77 non-tumor kidney tissues of kidney cancer patients with CKD (stages G1 to G5). In total, this analysis detected 697 single-nucleotide variants (SNVs) and 504 indels as heteroplasmic (0.5% ≤ variant allele frequency (VAF) < 95%), and the total number of detected SNVs/indels did not differ between CKD stages. However, the number of deleterious low-level heteroplasmic variants (pathogenic missense, nonsense, frameshift and tRNA) significantly increased with CKD progression (p < 0.01). In addition, mtDNA copy numbers (mtDNA-CNs) decreased with CKD progression (p < 0.001). This study demonstrates that mtDNA damage, which affects mitochondrial genes, may be involved in reductions in mitochondrial mass and associated with CKD progression and kidney dysfunction.

Clinical significance of clinicopathological features in predicting surgical treatment and risk of complications in renal cancer with venous tumor thrombosis

Aim. To study and analyze the surgical results and prognostic factors accompanying radical nephrectomy combined with venous thrombectomy in renal cancer patients with venous tumor thrombosis.Materials and methods. Retrospective analysis of clinical data of patients with renal cancer and venous tumor thrombosis who underwent surgical treatment at the Clinic of Cardiovascular Surgery and the Clinic of Urology of the I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University) from May 2010 to February 2023. Kaplan–Meier analysis was used to obtain overall survival curves and log-rank tests were used for statistical comparisons; Cox regression models were used for multivariate analysis of survival and complications to find independent risk factors affecting prognosis.Results. A total of 42 patients were included, 15 patients with grade 0–II tumor thrombosis and 27 patients with grade III–IV thrombosis. There were 3 perioperative deaths. The 5-year postoperative survival rate of patients was 68 %. Cox regression analysis: stage Т: HR = 0.515, 95 % confidential interval (CI) 0.111–2.393, p = 0.397; stage N: HR = 1.430, 95 % CI 0.380–5.457, p = 0.592; stage М: HR = 3.312, 95 % CI 0.811–4.561, p = 0,138; time of operation: HR = 1.001, 95 % CI 0.997–1.004, p = 0.771.Conclusion. Kidney cancer patients with venous tumor thrombosis have better surgical treatment results, which may significantly improve their prognosis compared with non-operated patients. Stage N and stage M were important factors directly affecting patients’ survival (HR &gt;1), but the level of tumor thrombosis could not be a factor affecting patients’ survival (HR = 1), but p &gt;0.05, so it was not statistically significant. The level of tumor thrombosis and the duration of surgery affect the intraoperative blood loss, and the greater the intraoperative blood loss, the higher the stage of early postoperative complications and the worse the patient’s prognosis.

Investigation of active peptides from natural products that induce ER-stress-mediated apoptosis in cancer as potential therapeutics for kidney cancer, common in some genetic diseases: An in silico approach

Background: Endoplasmic reticulum (ER) stress initiates an unfolded protein response (UPR) to re-establish ER homeostasis as an adaptive pathway in cancer. However, persistent ER stress triggers the apoptotic pathway usually observed in kidney cancer (KC). The term KC actually refers to a number of distinct cancers. Kidney cancer is generally observed in a number of genetic diseases. Treatment options for KC have changed greatly over the years. The most commonly used tyrosine kinase inhibitors, TKI, show conflicting results regarding their beneficial effects on patients, as demonstrated in different KC patient cohort studies, indicating that the underlying molecular mechanisms involved in KC are more complex and likely need combined therapies able to modulate the activity of endoplasmic reticulum. Methods: The purpose of this research was to generate peptides from natural products in sillico that might be used as kidney cancer potential modulators. For this aim, several methods were used: Target prediction, protein hydrolysis, and protein-peptide molecular docking have all been used as techniques. Results: The network of critical KC genes is composed of C3AR1, CSNK2A2, ACE, DPP4, CAPN1, FPR2, HLA-A, and MMP2, together with predicted kinases such as RPS6KA5, MAPK14, CSNK2A1, PRKCD, CDK1, and HIPK2, in addition to transcription factors such as IRF8, TCF3, ERG, CREB1, EZH2, SPI1, IRF1, and SUZ12. The identified molecular targets of the isolated peptides are: HLA class I histocompatibility antigen A-3, lipoxin A4, dipeptidyl peptidase IV, angiotensinconverting enzyme, cyclooxygenase-2, C3a anaphylatoxin chemotactic receptor, melanocortin receptor 4, neurotensin receptor 1, mu opioid receptor, delta opioid receptor, and calpain 1. Conclusion: Overall, the results showed that GVSK, PGP, WQR, YGGF, and IF peptides are promising candidates for further study. Future work would be needed to test the therapeutic properties of these hydrolysate peptides using in vitro and in vivo approaches.

Desensitization protocol to nivolumab without corticosteroid use in a kidney cancer patient

Desensitization protocol to nivolumab without corticosteroid use in a kidney cancer patient

Hands-Free Proteomic Profiling of Urinary Extracellular Vesicles with a High-Throughput Automated Workflow.

Extracellular vesicles (EVs) have emerged as a promising source of disease biomarkers for noninvasive early stage diagnoses, but a bottleneck in EV sample processing restricts their immense potential in clinical applications. Existing methods are limited by a low EV yield and integrity, slow processing speeds, low sample capacity, and poor recovery efficiency. We aimed to address these issues with a high-throughput automated workflow for EV isolation, EV lysis, protein extraction, and protein denaturation. The automation can process clinical urine samples in parallel, resulting in protein-covered beads ready for various analytical methods, including immunoassays, protein quantitation assays, and mass spectrometry. Compared to the standard manual lysis method for contamination levels, efficiency, and consistency of EV isolation, the automated protocol shows reproducible and robust proteomic quantitation with less than a 10% median coefficient of variation. When we applied the method to clinical samples, we identified a total 3,793 unique proteins and 40,380 unique peptides, with 992 significantly upregulated proteins in kidney cancer patients versus healthy controls. These upregulated proteins were found to be involved in several important kidney cancer metabolic pathways also identified with a manual control. This hands-free workflow represents a practical EV extraction and profiling approach that can benefit both clinical and research applications, streamlining biomarker discovery, tumor monitoring, and early cancer diagnoses.

Predictors of disease recurrence in high-risk non-metastatic renal cell carcinoma patients post-surgical resection A single-center, retrospective study.

Approximately 20-40% of kidney cancer patients treated for localized disease experience post-surgical recurrence. Several prognostic models exist to help clinicians determine the risk of distant recurrence, but these models vary in criteria and endpoints. We aimed to examine the recurrence rate and clinicopathologic factors as predictors of recurrence in high-risk renal cell carcinoma (RCC) patients. We conducted a single-center, retrospective chart review of pT3 RCC patients who underwent a nephrectomy between January 2000 and December 2015. Patients registered in clinical trials for adjuvant therapy and those with fewer than three years of followup were excluded. Kaplan-Meier survival analysis and univariate and multivariate Cox regression were performed to identify the rate and predictors of disease recurrence. Eighty-eight pT3 RCC patients were included, and 39 patients had recurrence with a median of 23.5 months (range 1.6-127.5). Nine patients had disease recurrence beyond 58 months. Kaplan-Meier log-rank tests identified patients with negative surgical margins and low Fuhrman nuclear grades had greater recurrence-free survival. Univariate Cox regression revealed positive surgical margins, high Fuhrman nuclear grade, and large tumor sizes were significant predictors. In the multivariate Cox regression model, high Fuhrman nuclear grade and positive surgical margins were significant predictors of recurrence. Disease recurrence occurred in 44% of pT3-staged patients. High Fuhrman nuclear grade and positive surgical margins were associated with time to recurrence. Physicians should use prognostic models to facilitate conversations about disease recurrence and continue to monitor high-risk patients beyond the recommended five-year followup period. We recommend monitoring pT3 resected patients for up to 10 years post-surgery.

STK4 is a prognostic biomarker correlated with immune infiltrates in clear cell renal cell carcinoma.

Mammalian STE20-like kinase 1 (MST1/STK4/KRS2) is a highly conserved serine/threonine kinase and a central member of the Hippo signaling pathway. STK4 has been reported to play important roles in various tumors, but a systematic and comprehensive study of its function in clear cell renal cell carcinoma (ccRCC) has not been conducted. In this study, we used immunohistochemistry (IHC), western blot (WB), quantitative real-time PCR (qPCR) experiments, and bioinformatics analysis to comprehensively analyze the expression, prognostic value, and immune infiltration of STK4 in ccRCC. Analysis of the TCGA database showed that the expression level of the STK4 gene in ccRCC patients depended on tumor stage, grade, and distant lymphatic metastasis. This was further confirmed by the results of IHC, WB, and qPCR. In addition, we used the receiver operating characteristic curve (ROC curve) to elucidate the diagnostic value of STK4 in ccRCC patients. According to the findings of the TIMER database, the high expression of STK4 is significantly associated with the survival of kidney cancer (including ccRCC) patients (p < 0.001), suggesting that STK4 is a reliable prognostic predictor. We then used gene set enrichment analysis (GSEA) to explore the mechanisms behind STK4 function in ccRCC. We found that STK4 may play a role in immune regulation interactions. Subsequently, we performed immune infiltration analysis of STK4. The results showed that STK4 may regulate the development of ccRCC by affecting the immune infiltration of NK and pDC cells. STK4 may be a prognostic marker for ccRCC and may help identify new strategies for treating ccRCC patients.

Artificial intelligence in urologic oncology: the actual clinical practice results of IBM Watson for Oncology in South Korea

BackgroundArtificial intelligence (AI) is changing our life, including the medical field. Repeated machine learning using big data made various fields more predictable and accurate. In medicine, IBM Watson for Oncology (WFO), trained by Memorial Slone Kettering Cancer Center (MSKCC), was first introduced and applied in 14 countries worldwide.Our study was designed to assess the feasibility of WFO in actual clinical practice. We aimed to investigate the concordance rate between WFO and multidisciplinary tumor board (MTB) in Urologic cancer patients. Materials and methodsWe reviewed retrospectively collected data for consecutive patients who underwent WFO and MTB simultaneously in the diagnosis of urologic malignancy before determining further treatment between August 2017 and September 2020. We compared the recommendation of the AI system, WFO (IBM Watson Health, Cambridge, MA), with the opinion of MTB for further managing all patients diagnosed with urologic malignancies such as prostate, bladder, and kidney cancer. ResultsA total of 55 patients were enrolled in our study. The number of patients with prostate cancer was 48. The number of bladder and kidney cancer patients was 5 and 2, respectively. The overall concordance rate between WFO and MTB was 92.7%. Three patients could not suggest proper treatment options using WFO, and the recommended choice of WFO was not feasible in the Korean Health Insurance Review and Assessment Service. ConclusionsThe decision of WFO showed a high concordance rate with a multidisciplinary tumor board for urologic oncology. However, some recommendations of WFO were not feasible in actual practice, and WFO still has some points to improve and modify. Interestingly, applying WFO is likely to facilitate a multidisciplinary team approach.

Prevalence of primary and secondary hypertension among hospitalized patients with cancer in the United States.

Hypertension is the most common comorbidity in patients with cancer. We aimed to estimate the prevalence of hypertension by demographic characteristics and cancer type among hospitalized patients with cancer. Hospitalized cancer patients were included using 2016-2018 National Inpatient Sample data. The independent variable was the presence of hypertension, which was further classified as primary, secondary, and other hypertension. Patient characteristics were grouped by age, sex, race/ethnicity, and the 12 most common cancer types. Multinomial logistic regression was used. Among 638,670 hospitalized patients with cancer, 56.8% had hypertension. The predicted percentages of having any hypertension were higher with age, male gender, and black race. The predicted percentages of any hypertension were the highest in kidney cancer patients across all age and race/ethnicity groups. Uterine cancer was associated with the highest percentages of primary hypertension, followed by kidney cancer. Leukemia was associated with the highest percentages of secondary hypertension, followed by non-Hodgkin lymphoma. Kidney cancer patients had the highest predicted percentage of hypertension overall, while uterine cancer and leukemia had the highest percentages of primary and secondary hypertension, respectively. This study provides evidence for identifying cancer patients who need more attention for the prevention and management of hypertension.