Wilms Tumor Patients Research Articles

Two-hit mutation causes Wilms tumor in an individual with FBXW7-related neurodevelopmental syndrome.

FBXW7 (F-box and WD-repeat domain-containing 7) is a tumor suppressor gene, and its germline variants have been causally linked to Wilms tumors. Furthermore, germline variants of FBXW7 have also been implicated in a neurodevelopmental syndrome. However, little is known regarding the occurrence of Wilms tumor in patients with FBXW7-related neurodevelopmental syndrome. We identified a novel constitutional pathogenic variant of FBXW7 in a patient with intellectual disability, who also developed Wilms tumor. The variant was derived from his apparently normal mother, and was also detected in his sister who exhibited developmental delay. Furthermore, we detected a somatic nonsense variant on the paternal allele of FBXW7 in the tumor DNA. These results suggest that the development of Wilms tumor along with FBXW7-related neurodevelopmental syndrome follows the two-hit model, which needs to be validated to establish appropriate follow-up management and tumor surveillance.

Stratification of Wilms tumor patients using physicochemical properties of the adaptive immune receptor polypeptides, IGL and TRG

Wilms tumor (WT) is the most common pediatric renal malignancy. Current guidelines that stratify WT risk and determine treatment courses are inadequate, as over 60% of WT survivors develop treatment-related complications. Recently, numerous advances in establishing patient sub-groups with different clinical features have been realized by evaluating the adaptive immune receptor (IR) complementarity determining region-3 (CDR3) amino acid (AA) sequences, a reasonable series of successes, given the prominent role of the CDR3 in antigen binding, including tumor antigen binding. However, the possibility that adaptive IR chemical variability correlates with distinct survival outcomes for WT has not yet been explored. The goal of this study was to isolate the T-cell receptor and B-cell receptor recombination, sequencing reads from WT RNAseq files, representing the actual tumor tissue, translate the sequences to AAs, identify the adaptive IR CDR3 domains, and determine whether the physicochemical properties of those CDR3 AA sequences correlated with survival probability distinctions. WT RNA-seq files were mined to obtain the CDR3 AAs for various adaptive IRs. The physicochemical properties of these CDR3s were examined for trends in how those properties correlated with survival probabilities for WT patients, using a Kaplan-Meier analyses, verified via several approaches. The above processes indicated the association of the (a) IGL CDR3s' instability index and the (b) TRG CDR3s' fraction disorder promoting features with better outcomes. Additionally, the IGL CDR3 data were assessed using the Predictor of Natural Disordered Regions web tool, which strengthened the evidence for the association with the IGL CDR3 instability index with a better outcome. The approaches described here indicate that greater adaptive IR CDR3 instability and flexibility may serve as prognostic indicators; and may indicate the flexibility of CDR3 domains provides for greater opportunity to bind tumor antigens. Further exploration and development of these approaches and findings may lead to new guidelines for more precise treatment regimens, or even watchful waiting periods, that could thereby decrease the lifetime occurrence of adverse events.

Survival characteristics of Wilms Tumor, a reference developed from a longitudinal cohort study

BackgroundWilms tumor (WT) survival has been affected by the evolution in clinical and biological prognostic factors. Significant differences in survival rates indicate the need for further efforts to reduce these disparities. This study aims to evaluate the clinicopathological data impact on survival among patients after Wilm's diagnosis.MethodsThe study utilized the SEERStat Database to identify Wilms tumor patients, applying SEERStat software version 8.3.9.2 for data extraction. Selection criteria involved specific codes based on the International Classification of Diseases for Oncology (ICDO-3), excluding cases with unknown SEER stage, incomplete survival data, unknown size, or lymph node status. Statistical analyses, including Kaplan–Meier estimates and Cox regression models, were conducted using R software version 3.5. Standardized mortality ratios (SMR) were computed with SEER*Stat software, and relative and conditional survival analyses were performed to evaluate long-term survival outcomes.ResultsOf 2273 patients diagnosed with Wilms tumor, (1219 patients, 53.6% were females with an average age group of 3–8 years (50.2%). The overall mean survival after five years of diagnosis was 93.6% (2.6–94.7), and the overall mean survival rate was 92.5% (91.3–93.8) after ten years of diagnosis. Renal cancers were identified as the leading cause of death (77.3%), followed by nonrenal cancers (11%) and noncancer causes (11%). Additionally, robust relative survival rates of 98.10%, 92.80%, and 91.3% at one, five, and ten years, respectively, were observed, with corresponding five-year conditional survival rates indicating an increasing likelihood of survival with each additional year post-diagnosis. Univariate Cox regression identified significant prognostic factors: superior CSS for patients below 3 years (cHR 0.48) and poorer CSS for those older than 15 years (cHR 2.72), distant spread (cHR 10.24), regional spread (cHR 3.09), and unknown stage (cHR 4.97). In the multivariate model, age was not a significant predictor, but distant spread (aHR 9.22), regional spread (aHR 2.84), and unknown stage (aHR 4.98) were associated with worse CSS compared to localized tumors.ConclusionThis study delving into WT survival dynamics reveals a multifaceted landscape influenced by clinicopathological variables. This comprehensive understanding emphasizes the imperative for ongoing research and personalized interventions to refine survival rates and address nuanced challenges across age, stage, and tumor spread in WT patients.

Long-term outcomes and patterns of relapse in patients with bilateral Wilms tumor or bilaterally predisposed unilateral Wilms tumor, a report from the COG AREN0534 study.

The objective of this study is to report the long-term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event-free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre-specified groups. Two hundred and twenty-two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8-year EFS was 75% (95% confidence interval: 69%-83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow-up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post-chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis.

Increasing abdominal circumference in children – does it require diagnosis?

Introduction and purpose: Wilms tumor, also known as nephroblastoma, is the most prevalent malignant tumor of the kidney in the pediatric population. 90% of them are diagnosed in children before the age of 6. This tumor is more common in girls, and usually occurs unilaterally. The purpose of the study is to analyse and present the incidence of the patients with Wilms tumor in University Children’s Hospital in Lublin in comparison to other studies published on PubMed. Material and methods: The study included 34 patients with the Wilms tumor in the past medical history. They were selected among patients who had a computed tomography (CT) scan in the Department of Pediatric Radiology between November 2012 and October 2021. Results: The average diagnostic age of Wilms tumor patients was 3 years and 9 months. The unilateral occurrence of the tumor was more common, also, the presence of a tumor in the left kidney was more frequent than in the right one. Metastases were mainly located in the lungs and liver. The less common sites of metastasis were pleural recesses and paraaortic lymph nodes. Treatment was mostly based on nephrectomy and chemotherapy, and less frequently, on radiotherapy. In the majority of patients, treatment resulted in regression of cancer lesions. Only a few recurrences of the disease were reported. Conclusions: Successful treatment protocols for Wilms tumor (pre-operative chemotherapy and surgery) ensure a high survival rate. It is important to monitor the patient after treatment due to the risk of recurrence. During diagnostics, chest and abdominal CT should be considered because of the high incidence rate of lung and liver metastases.

Wilms tumor treatment protocol compliance and the influence on outcomes for children in Tanzania.

Standardized Wilms tumor treatment protocols exist for low- and middle-income countries, but outcomes equivalent to high-income countries are not achieved outside of clinical trials. As Wilms tumor treatment protocols in Africa shift with increasing resource capacity, it is not known how treatment compliance to each stage of therapy affects outcomes and where the critical breakpoints are for protocol adherence in clinical practice. We describe both treatment outcomes and treatment protocol adherence in a retrospective single-center cohort study of pediatric Wilms tumor patients at a zonal cancer referral hospital in Tanzania from 2016 to 2019, treated per the International Society of Paediatric Oncology standard (2016-2017) or Tanzania adapted (2018-2019) therapy protocols. A total of 69 patients were evaluated. The two-year overall survival and event-free survival rates were 40% and 29%, respectively. Only 29% of patients completed recommended chemotherapy per protocol, and completion of preoperative and postoperative chemotherapy was predictive of two-year overall survival (odds ratio [OR] 14.4, p<.001). There were delays at almost every stage of treatment, especially time from preoperative chemotherapy to surgery (56days), from surgery to pathology report (30days), and from surgery to initiation of postoperative chemotherapy (38days). Nonadherence with recommended Wilms tumor treatment guidelines due to key health system delays correlated to reduced overall survival rates, with chemotherapy nonadherence due to abandonment, lack of surgery, and deaths on therapy as the strongest contributors. Future interventions targeting health system delays and reducing deaths during therapy are critical to improving protocol compliance and increasing overall survival for pediatric Wilms tumor patients in low-resource settings.

Factors Associated with Survival in Wilms Tumor Patients

Introduction: Wilms tumor is the second most common abdominal tumor in the pediatric age group and accounts for more than 90% of renal tumors in pediatrics. Even though the described survival rate is greater than 90%, we found that it only reaches 70% among our patients. Therefore, we aim to evaluate which are the factors associated with these unfavorable results, in order to implement measures to improve the survival of our patients. Methods: An observational, cross-sectional study was conducted in two high-level care centers, which included a sample of 84 patients under 15 years of age, diagnosed with Wilms tumor. Results: Factors significantly associated with an increased likelihood of death were failure to complete the chemotherapy protocol (odds ratio [OR] = 34; 95% confidence interval [CI] = 3.7–312; P = 0.000) and tumor recurrence (OR = 35.7; 95% CI = 6.9–184; P = 0.000). Other minor factors with certain impact were bilateral presentation (OR = 4.1; 95% CI = 0.6–5.5; P = 0.147), surgical complications (OR = 3.2; 95% CI = 0.7–14.6; P = 0.136), lymph node involvement on CT scan (OR 2.4; 95% CI 0.7­–8.4; P = 0.139), and distant metastases (OR = 2.5; 95%CI = 0.7–9; P = 0.143). Discussion: The survival of our patients with Wilms tumor is lower than that reported in literature is associated with factors like failure to complete chemotherapy, recurrence, and the need for bilateral surgery.

Radiologic versus Segmentation Measurements to Quantify Wilms Tumor Volume on MRI in Pediatric Patients.

Wilms tumor is a common pediatric solid tumor. To evaluate tumor response to chemotherapy and decide whether nephron-sparing surgery is possible, tumor volume measurements based on magnetic resonance imaging (MRI) are important. Currently, radiological volume measurements are based on measuring tumor dimensions in three directions. Manual segmentation-based volume measurements might be more accurate, but this process is time-consuming and user-dependent. The aim of this study was to investigate whether manual segmentation-based volume measurements are more accurate and to explore whether these segmentations can be automated using deep learning. We included the MRI images of 45 Wilms tumor patients (age 0-18 years). First, we compared radiological tumor volumes with manual segmentation-based tumor volume measurements. Next, we created an automated segmentation method by training a nnU-Net in a five-fold cross-validation. Segmentation quality was validated by comparing the automated segmentation with the manually created ground truth segmentations, using Dice scores and the 95th percentile of the Hausdorff distances (HD95). On average, manual tumor segmentations result in larger tumor volumes. For automated segmentation, the median dice was 0.90. The median HD95 was 7.2 mm. We showed that radiological volume measurements underestimated tumor volume by about 10% when compared to manual segmentation-based volume measurements. Deep learning can potentially be used to replace manual segmentation to benefit from accurate volume measurements without time and observer constraints.

Direct correlation of MRI with histopathology in pediatric renal tumors through the use of a patient-specific 3-D-printed cutting guide: a feasibility study

BackgroundPediatric renal tumors are often heterogeneous lesions with variable regions of distinct histopathology. Direct comparison between in vivo imaging and ex vivo histopathology might be useful for identification of discriminating imaging features.ObjectiveThis feasibility study explored the use of a patient-specific three-dimensional (3D)-printed cutting guide to ensure correct alignment (orientation and slice thickness) between magnetic resonance imaging (MRI) and histopathology.Materials and methodsBefore total nephrectomy, a patient-specific cutting guide based on each patient’s preoperative renal MRI was generated and 3-D printed, to enable consistent transverse orientation of the histological specimen slices with MRI slices. This was expected to result in macroscopic slices of 5 mm each. The feasibility of the technique was determined qualitatively, through questionnaires administered to involved experts, and quantitatively, based on structured measurements including overlap calculation using the dice similarity coefficient.ResultsThe cutting guide was used in eight Wilms tumor patients receiving a total nephrectomy, after preoperative chemotherapy. The median age at diagnosis was 50 months (range: 4–100 months). The positioning and slicing of the specimens were rated overall as easy and the median macroscopic slice thickness of each specimen ranged from 5 to 6 mm. Tumor consistency strongly influenced the practical application of the cutting guide. Digital correlation of a total of 32 slices resulted in a median dice similarity coefficient of 0.912 (range: 0.530–0.960).ConclusionWe report the feasibility of a patient-specific 3-D-printed MRI-based cutting guide for pediatric renal tumors, allowing improvement of the correlation of MRI and histopathology in future studies.

Patient-specific hydrogel phantoms for the preoperative simulation of nephron-sparing surgery in Wilms’ tumor patients: A feasibility study

Nephron-sparing surgery (NSS) for Wilms Tumor patients has a positive surgical margin rate of 15.7–36.4%. Innovative approaches may reduce the occurrence of positive surgical margins in NSS and prevent these children from having additional radiotherapy and chemotherapy. The feasibility of performing mock surgery on patient-specific hydrogel phantoms of the kidney, tumor, and arterial vasculature for preoperative simulation of NSS was assessed in two patients. The development of patient-specific phantoms allowed the surgeon to practice surgery. Moreover, phantom specimens were assessed using MRI to understand the location and size of the smallest surgical margin. Surgeons reported that simulation surgery helped perform NSS safely and improved intraoperative tumor localization and resection planning. The technique is considered feasible and useful when preparing for NSS. In the future, this technique may further help to achieve negative surgical margins in NSS and may also allow the use of NSS in patients typically regarded as ineligible for this procedure.

Downregulated TICAM1 is a prognostic biomarker and associated with immune tolerance of Wilms tumor patients

BackgroundTIR domain containing adaptor molecule 1 (TICAM1) is a coding gene participating in immune and inflammation responses to malignant cells. However, the role of TICAM1 in Wilms tumor (WT) is rarely known.Materials and methodsThe expression level of TICAM1 was calculated in the WT TARGET cohort and validated using the GSE66405 cohort. The Kaplan–Meier method was employed to investigate the potential clinical value of TICAM1 and the association between its expression level and clinical features. The influence of TICAM1 on immune infiltration was examined by ESTIMATE, CIBERSORT and MCPcounter algorithms. IC50 of chemotherapeutic drugs was calculated by “pRRophetic” R package.ResultsTICAM1 was downregulated in WT patients with worse prognosis and a more advanced clinical stage. Moreover, a low expression level of TICAM1 contributed to less immune cell infiltration, few protective immune cells and more antitumor immune cells.ConclusionsTICAM1 exerts a significant impact on the prognosis, progression and immune infiltration condition of WT.

The clinical impact of observer variability in lung nodule classification in children with Wilms tumour.

To investigate the extent to which observer variability of computed tomography (CT) lung nodule assessment may affect clinical treatment stratification in Wilms tumour (WT) patients, according to the recent Société Internationale d'Oncologie Pédiatrique Renal Tumour Study Group (SIOP-RTSG) UMBRELLA protocol. I: CT thoraces of children with WT submitted for central review were used to estimate size distribution of lung metastases. II: Scans were selected for blinded review by five radiologists to determine intra- and inter-observer variability. They assessed identical scans on two occasions 6months apart. III: Monte Carlo simulation (MCMC) was used to predict the clinical impact of observer variation when applying the UMBRELLA protocol size criteria. Lung nodules were found in 84 out of 360 (23%) children with WT. For 21 identified lung nodules, inter-observer limits of agreement (LOA) for the five readers were ±2.4 and ±1.4mm (AP diameter), ±1.9 and ±1.8mm (TS diameter) and ±2.0 and ±2.4mm (LS diameter) at assessments 1 and 2. Intra-observer LOA across the three dimensions were ±1.5, ±2.2, ±3.5, ±3.1 and ±2.6mm (readers 1-5). MCMC demonstrated that 17% of the patients with a 'true' nodule size of ≥3mm will be scored as <3mm, and 21% of the patients with a 'true' nodule size of <3mm will be scored as being ≥3mm. A significant intra-inter observer variation was found when measuring lung nodules on CT for patients with WT. This may have significant implications on treatment stratification, and thereby outcome, when applying a threshold of ≥3mm for a lung nodule to dictate metastatic status.

White paper: Oncofertility in pediatric patients with Wilms tumor.

The survival of childhood Wilms tumor is currently around 90%, with many survivors reaching reproductive age. Chemotherapy and radiotherapy are established risk factors for gonadal damage and are used in both COG and SIOP Wilms tumor treatment protocols. The risk of infertility in Wilms tumor patients is low but increases with intensification of treatment including the use of alkylating agents, whole abdominal radiation or radiotherapy to the pelvis. Both COG and SIOP protocols aim to limit the use of gonadotoxic treatment, but unfortunately this cannot be avoided in all patients. Infertility is considered one of the most important late effects of childhood cancer treatment by patients and their families. Thus, timely discussion of gonadal damage risk and fertility preservation options is important. Additionally, irrespective of the choice for preservation, consultation with a fertility preservation (FP) team is associated with decreased patient and family regret and better quality of life. Current guidelines recommend early discussion of the impact of therapy on potential fertility. Since most patients with Wilms tumors are prepubertal, potential FP methods for this group are still considered experimental. There are no proven methods for FP for prepubertal males (testicular biopsy for cryopreservation is experimental), and there is just a single option for prepubertal females (ovarian tissue cryopreservation), posing both technical and ethical challenges. Identification of genetic markers of susceptibility to gonadotoxic therapy may help to stratify patient risk of gonadal damage and identify patients most likely to benefit from FP methods.

Wilms tumour treatment in Sudan: A 10-year single-centre experience.

In Sudan, the survival of Wilms tumour was reported as 11% in a 2008 study. The impact of establishing paediatric oncology service on survival is studied, and the obstacles of treating Wilms tumour patients were identified. This study investigates Wilms tumour treatment outcomes over 10 years at Khartoum Oncology Hospital (KOH). All Wilms tumour patients from 2005 to 2014 were analysed retrospectively. Patients received treatment based on the NWTS IV protocol. Patients were analysed for overall survival, and event-free survival and these outcomes were correlated with age, sex, stage at presentation, and histology. We analysed 143 files of Wilms tumour patients. The male to female ratio is 1.75. The mean age of patients at diagnosis is 3.5 years. The follow-up period is 5 years. Most patients (83%) had advanced disease stage 3, and 4. There is a very high abandonment rate 61 (42.6%). The event-free survival among patients who completed treatment is 75.6%, and is 43.4% for all the (143) patients. "After initiation of the paediatric oncology service, the survival of Wilms tumour in Sudan is 43%. Abandonment of treatment remains high. Opportunity remains to reduce abandonment and establish a surgical paediatric oncology service to improve outcomes further."

Virtual Resection: A New Tool for Preparing for Nephron-Sparing Surgery in Wilms Tumor Patients.

Nephron-sparing surgery (NSS) in Wilms tumor (WT) patients is a surgically challenging procedure used in highly selective cases only. Virtual resections can be used for preoperative planning of NSS to estimate the remnant renal volume (RRV) and to virtually mimic radical tumor resection. In this single-center evaluation study, virtual resection for NSS planning and the user experience were evaluated. Virtual resection was performed in nine WT patient cases by two pediatric surgeons and one pediatric urologist. Pre- and postoperative MRI scans were used for 3D visualization. The virtual RRV was acquired after performing virtual resection and a questionnaire was used to assess the ease of use. The actual RRV was derived from the postoperative 3D visualization and compared with the derived virtual RRV. Virtual resection resulted in virtual RRVs that matched nearly perfectly with the actual RRVs. According to the questionnaire, virtual resection appeared to be straightforward and was not considered to be difficult. This study demonstrated the potential of virtual resection as a new planning tool to estimate the RRV after NSS in WT patients. Future research should further evaluate the clinical relevance of virtual resection by relating it to surgical outcome.

Improvement of survival in Wilms Tumor patients at the paediatric oncology unit, KATH

BackgroundWilms Tumor (WT) is one of the common and curable cancer types targeted by the World Health Organization (WHO) Global initiative for childhood cancer (GICC). Although, survival in high income countries is good, the same cannot be said of survival in low- and middle-income countries (LMIC) like Ghana. The main aim of this study was to determine the clinical presentation and survival of patients with WT presenting at the Komfo Anokye Teaching Hospital MethodsThis research is a 5-year (2016 - 2020) prospective hospital based cross sectional study. Patient characteristics, tumor characteristics and outcome were described, and survival analysis was done. The survival was compared to a historical cohort (2011- 2013) which was evaluated in 2015 where 18.5% of patients survived. ResultsA total of 51 patients were seen over the 5-year period with a male to female ratio of 1.2:1. The median age of presentation was 3years. Majority of patients (56.5%) presented with a left sided renal mass. A significant proportion presented with Stage III (37.1%) and Stage IV (20.98%) disease. The commonest site of metastasis was the liver with 19.4% of patients presenting with it. Thirty three percent (33%) of the patients died with 8(47%) occurring before initiation of treatment. Mortality was highest amongst patients with advanced disease with a p-value of 0.19. The 3-year event free survival with abandonment as an event in patients seen from 2016 - 2019 was 55.6% (p-0.026). ConclusionPatients with high stage tumors (Stage III and IV) were at a higher risk of death as compared to the patients with lower stage tumors. Early detection and treatment of patients with WT can lead to a favorable outcome.

Evaluation of Interstitial Cells of Cajal-Like Cells at the Pelviureteric Junction in Children with Pelviureteric Junction Obstruction: A Prospective Study and Review of Literature.

Introduction:The etiopathogenesis of pelviureteric junction obstruction (PUJO) has been debated. Recently, the role of interstitial cells of Cajal-like cells (ICC-LC)has been studied and reported to be the cause of this functional obstruction. We studied the histopathology and ICC-LC density at PUJ and compared it with that of PUJ of the control group and distal ureteric margin of the study group.Methods:A prospective study was conducted which included PUJO patients in the study group and the renal tumor patients in the control group. Histopathological examination (muscle hypertrophy and fibrosis) and immunohistochemistry (ICC-LC density) were done. The muscle hypertrophy, fibrosis, and ICC-LC density at the PUJ in both the groups were compared. A similar comparison was performed between the findings at the PUJ and the distal margin in the study group.Results:The study and control groups included 37 PUJO patients and 13 Wilms tumor patients. The ICC-LC density at PUJ in the study group was significantly lower than that in the control group (P < 0.001) and that at the distal resected margin of the study group (P < 0.001). Significantly increased muscle hypertrophy (P < 0.001) and fibrosis (P = 0.002) were seen at PUJ in the study group compared to the control group. No significant association was noted between the ICC-LC density and muscle hypertrophy at PUJ and the distal resected margin in the study group.Conclusion:A significant decrease in the density of ICC-LC and increased fibrosis and muscle hypertrophy at PUJ in children with PUJO play a role in the etiopathogenesis of the disease.

Macrophages and monocytes mediated activation of oxidative phosphorylation implicated the prognosis and clinical therapeutic strategy of Wilms tumour

Wilms tumour is the fourth leading cause of paediatric malignancy, but the detailed relationship between the tumour microenvironment and prognosis remains largely unclear. In this research, gene expression profile and clinical information from TARGET and the First Affiliated Hospital of Anhui Medical University were collected. After comparing the prognostic value of the associated immune cells, we established a nomogram to predict the prognosis of Wilms tumour based on monocyte infiltration, macrophage infiltration, stage, and sex. Further results showed that the most significant relationship between matrix metallopeptidase 9 and prognosis or macrophage infiltration. Meanwhile, by gene set enrichment or variation analyses and immunohistochemistry staining, we demonstrated that the most highly enriched hub genes were closely related to the activated oxidative phosphorylation pathway. Finally, through tumour immune dysfunction and an exclusion algorithm, the satisfactory discriminative performance of our nomogram was revealed for predicting the response to clinical therapy. Anti-PD1 therapy is more suitable for Wilms tumour patients with high nomogram points, and chemotherapies are more effective for patients with low nomogram score.

DNA Methylation Data-Based Classification and Identification of Prognostic Signature of Children With Wilms Tumor.

Background: As an epigenetic alteration, DNA methylation plays an important role in early Wilms tumorigenesis and is possibly used as marker to improve the diagnosis and classification of tumor heterogeneity. Methods: Methylation data, RNA-sequencing (RNA-seq) data, and corresponding clinical information were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. The prognostic values of DNA methylation subtypes in Wilms tumor were identified. Results: Four prognostic subtypes of Wilms tumor patients were identified by consensus cluster analysis performed on 312 independent prognostic CpG sites. Cluster one showed the best prognosis, whereas Cluster two represented the worst prognosis. Unique CpG sites identified in Cluster one that were not identified in other subtypes were assessed to construct a prognostic signature. The prognostic methylation risk score was closely related to prognosis, and the area under the curve (AUC) was 0.802. Furthermore, the risk score based on prognostic signature was identified as an independent prognostic factor for Wilms tumor in univariate and multivariate Cox regression analyses. Finally, the abundance of B cell infiltration was higher in the low-risk group than in the high-risk group, based on the methylation data. Conclusion: Collectively, we divided Wilms tumor cases into four prognostic subtypes, which could efficiently identify high-risk Wilms tumor patients. Prognostic methylation risk scores that were significantly associated with the adverse clinical outcomes were established, and this prognostic signature was able to predict the prognosis of Wilms tumor in children, which may be useful in guiding clinicians in therapeutic decision-making. Further independent studies are needed to validate and advance this hypothesis.

Roles of hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha, a lipid metabolism enzyme, in Wilms tumor patients.

Wilms tumor is a common pediatric malignant tumor that accounts for approximately 95% of kidney tumors in children. The role of lipid metabolism in tumors has attracted increased attention in recent years. We examined the role of hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA), a lipid metabolism enzyme, in the pathogenesis of Wilms tumor. In a previous study, we screened Wilms tumors and adjacent normal tissues for differentially expressed proteins by mass spectrometry and verified the results by western blot analysis. The Oncomine database and quantitative reverse transcription-polymerase chain reaction were used to verify the expression of HADHA at the genetic level. Immunohistochemistry and immunofluorescence were also used to validate the differential expression of the HADHA protein. The relationship between histopathological typing, clinical pathology, and HADHA expression was analyzed in 65 paraffin-embedded specimens from pediatric Wilms tumor patients. Kaplan-Meier survival curves were used to analyze the relationship between the expression of HADHA and patient prognosis. HADHA was expressed at low levels in Wilms tumor tissue compared with the corresponding normal tissue. The expression of HADHA was closely associated with histopathological typing (P = 0.030). The prognostic analysis of 65 children with Wilms tumor showed that high expression of HADHA was closely associated with poor prognosis (P = 0.046). HADHA expression is downregulated in Wilms tumor tissues, but high expression in tumor tissues is associated with clinical stage and the prognosis of children with this tumor.