Efficacy and late kidney effects of nephron-sparing surgery in the management of unilateral Wilms tumor: a systematic review and meta-analysis.

To evaluate the efficiency and long-term renal function of nephron sparing surgery (NSS) in unilateral WT patients compared with radical nephrectomy (RN). The review was performed following Cochrane Handbook guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched five databases (Pubmed, Embase, Scopus, Web of Science and Cochrane) for studies reporting the efficiency and late renal function of NSS and/or RN on February 10, 2023. Comparative studies were evaluated by Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) and RoB 2.0. Assessed outcomes included survival rate, relapse rate, eGFR, renal dysfunction and hypertension. 26 studies involving 10322 unilateral WT cases underwent RN and 657 unilateral WT cases underwent NSS were enrolled. Overall effect estimates demonstrated that NSS significantly increased eGFR at follow-up (SMD, 0.38; 95% CI 0.05-0.72; p = 0.025) compared to that at diagnosis, and RN did not significantly decrease eGFR at follow-up (SMD, - 0.33; 95% CI - 0.77-0.11; p = 0.142) compared to that at diagnosis. Moreover, no significant difference was found in outcomes of survivability (OR, 1.38; 95% CI 0.82-2.32; p = 0.226), recurrence (OR, 0.62; 95% CI 0.34-1.12; p = 0.114), eGFR at follow-up (SMD, 0.16; 95% CI - 0.36-0.69; p = 0.538), renal dysfunction (OR, 0.36; 95% CI 0.07-1.73; p = 0.200) and hypertension (OR, 0.17; 95% CI 0.03-1.10; p = 0.063). Current evidence suggests that NSS is safe and effective for unilateral WT patients, because it causes better renal function and similar oncological outcomes compared with RN. Future efforts to conduct more high-quality studies and explore sources of heterogeneity is recommended.

Multiple transcriptome analysis of Piwil2-induced cancer stem cells, including piRNAs, mRNAs and miRNAs reveals the mechanism of tumorigenesis and development.

BACKGROUND: Cancer stem cells play important roles in the process of tumorigenesis. Our research group obtained cancer stem cell-like cells named Piwil2-iCSCs by reprogramming human preputial fibroblasts (FBs) with the PIWIL2 gene, but the mechanism of Piwil2-iCSCs is still unclear. METHODS: We sequenced the piRNAs, miRNAs and mRNAs of Piwil2-iCSCs and FBs, and analyzed the differences. Gene Ontology (GO) and, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and gene set enrichment analysis (GSEA) were performed on the differentially expressed (DE) mRNAs. In addition, we analyzed the variable shear events and fusion genes in the Piwil2-iCSCs. Target gene prediction and functional enrichment analysis were performed for the DE miRNAs. RESULTS: A total of 1119 DE mRNAs, 220 DE piRNAs, and 440 DE miRNAs were obtained between the Piwil2-iCSCs and FBs. Functional enrichment analysis showed that the genes with upregulated expression were mainly involved in DNA repair, mismatch repair, base excision repair, and nucleotide excision repair. Genes with downregulated expression were mainly involved in the TGF-ß receptor signaling pathway, senescence and autophagy in cancer. More frequent shear events occurred in Piwil2-iCSCs and FBs, especially in intron retention (IR) events. We also identified three fusion genes MCM3AP-C21orf58, LRRFIP2-CAV3 and TMEM184B-DMC1. Enrichment analysis of DE miRNAs showed that they were associated with apoptosis, the TGF-ß signaling pathway, and the stem cell regulatory signaling pathway. In particular, target gene prediction of the top three miRNAs with upregulated expression showed that they targeted SMAD, GREM1 and other genes to participate in the regulation of TGF-ß and other pathways. CONCLUSION: PIWIL2-induced cancer stem cells have significantly altered levels of miRNAs, piRNAs and mRNAs.TGF-ß, autophagy, apoptosis and other pathways may play an important role in stem cell development. The occurrence of alternative splicing and fusion genes may be related to the occurrence of cancer stem cells.

Development and validation of a nomogram to predict cancer-specific survival in elderly patients with papillary thyroid carcinoma: a population-based study.

OBJECTIVE: Thyroid carcinoma (TC) is the most common endocrine tumor in the human body. Papillary thyroid carcinoma (PTC) accounts for more than 80% of thyroid cancers. Accurate prediction of elderly PTC can help reduce the mortality of patients. We aimed to construct a nomogram predicting cancer-specific survival (CSS) in elderly patients with PTC. METHODS: Patient information was downloaded from the Surveillance, Epidemiology, and End Results (SEER) program. Univariate and multivariate Cox regression models were used to screen the independent risk factors for patients with PTC. The nomogram of elderly patients with PTC was constructed based on the multivariate Cox regression model. We used the concordance index (C-index), the area under the receiver operating characteristic curve (AUC) and the calibration curve to test the accuracy and discrimination of the prediction model. Decision curve analysis (DCA) was used to test the clinical value of the model. RESULTS: A total of 14,138 elderly patients with PTC were included in this study. Patients from 2004 to 2015 were randomly divided into a training set (N = 7379) and a validation set (N = 3141), and data from 2016 to 2018 were divided into an external validation set (N = 3618). Proportional sub-distribution hazard model showed that age, sex, tumor size, histological grade, TNM stage, surgery and chemotherapy were independent risk factors for prognosis. In the training set, validation set and external validation set, the C-index was 0.87(95%CI: 0.852-0.888), 0.891(95%CI: 0.866-0.916) and 0.931(95%CI:0.894-0.968), respectively, indicating that the nomogram had good discrimination. Calibration curves and AUC suggest that the prediction model has good discrimination and accuracy. CONCLUSIONS: We constructed a new nomogram to predict CSS in elderly patients with PTC. Internal cross-validation and external validation indicate that the model has good discrimination and accuracy. The predictive model can help doctors and patients make clinical decisions.

Antitumor effect of Escherichia coli-derived outer membrane vesicles on neuroblastoma in vitro and in vivo.

Bacterial outer membrane vesicles (OMVs) are spherical microbubbles that contain biological content and are produced by gram-negative bacteria. The use of OMVs as adjuvants for cancer immunotherapy or as drug carriers for targeted therapies has attracted the interest of many scholars. However, it is unclear whether OMVs can exert direct antitumor effects and whether OMVs can inhibit pediatric tumors. Here, we explore the potential of Escherichia coli-derived OMVs to directly suppress neuroblastoma. Our results demonstrate the antitumor effects of OMVs in vitro and in vivo, and no serious adverse reactions were observed. OMV uptake into the cytoplasm and nucleus directly decreases cell stemness, DNA damage, apoptosis and cell cycle arrest, which may be the mechanisms by which OMVs suppress tumors. Our results demonstrate the potential of bacterial OMVs to be used as antitumor adjuvant therapies, increasing the number of candidates for the development of cancer therapies in the future. More relevant studies are urgently needed to demonstrate the efficacy and safety of OMVs.

Prognosis of testicular torsion orchiopexy.

The purpose of this study was to follow up patients who underwent testicular torsion orchiopexies in order to observe whether testicular atrophy had occurred and to identify any influencing factors regarding atrophy. Patient data collected in this study included age, symptom duration, pre-operative preparation time, cryptorchidism testicular torsion, spermatic cord torsion degree, ultrasound findings at least 6 months after orchiopexy, testicular atrophy, mean platelet volume (MPV), address and medical insurance. Twenty-nine patients with a mean age of 147 (126.5-163) months involved in our study. The duration of follow-up ranged from 6 to 33 months with a median follow-up duration of 12 (8.5-21) months. Only MPV was significantly different between the atrophy group and nonatrophic group (p = .022) and the receiver operating characteristic (ROC) curve revealed that the cut-off value for MPV atrophy was 9.9 fl, with a sensitivity of 81.8% and a specificity of 70.6%. In conclusion, we found that 41.4% patients eventually experienced testicular atrophy after performing the testicular salvage procedure. MPV might be used as an indicator of testicular atrophy after an operation; however, the accuracy of MPV needs to be confirmed using significant follow-up prospective studies.

Doxycycline hydrochloride inhibits the progress of malignant rhabdoid tumor of kidney by targeting MMP17 and MMP1 through PI3K-Akt signaling pathway.

OBJECTIVE: To identify therapeutic targets for malignant rhabdoid tumors of kidney (MRTK) and to investigate the effects and underlying mechanism of doxycycline hydrochloride on these tumors. METHODS: Gene expression and clinical data of MRTK were retrieved from the TARGET database. Differentially expressed genes (DEGs) and prognostic-related genes (PRGs) were selected through a combination of statistical analyses. The functional roles of MMP17 and MMP1 were elucidated through RNA overexpression and intervention experiments. Furthermore, in vitro and in vivo studies provided evidence for the inhibitory effect of doxycycline hydrochloride on MRTK. Additionally, transcriptome sequencing was employed to investigate the underlying molecular mechanisms. RESULTS: 3507 DEGs and 690 PRGs in MRTK were identified. Among these, we focused on 41 highly expressed genes associated with poor prognosis and revealed their involvement in extracellular matrix regulatory pathways. Notably, MMP17 and MMP1 stood out as particularly influential genes. When these genes were knocked out, a significant inhibition of proliferation, invasion and migration was observed in G401 cells. Furthermore, our study explored the impact of the matrix metalloproteinase inhibitor, doxycycline hydrochloride, on the malignant progression of G401 both in vitro and in vivo. Combined with sequencing data, the results indicated that doxycycline hydrochloride effectively inhibited MRTK progression, due to its ability to suppress the expression of MMP17 and MMP1 through the PI3K-Akt signaling pathway. CONCLUSION: Doxycycline hydrochloride inhibits the expression of MMP17 and MMP1 through the PI3K-Akt signaling pathway, thereby inhibiting the malignant progression of MRTK in vivo and in vitro.

Survival benefits and challenges of adjuvant chemotherapy for high-grade osteosarcoma: a population-based study.

BACKGROUND: Osteosarcoma is the most prevalent primary malignant bone tumor. The primary treatment for osteosarcoma is a combination of chemotherapy and surgery. However, there has been no recent progress in the role of chemotherapy in improving the long-term survival of osteosarcoma patients. This study aims to analyze the factors that affect chemotherapy in patients with osteosarcoma and explore the challenges and survival benefits of chemotherapy. METHODS: Patient data were downloaded from The Surveillance, Epidemiology, and End Results database. Univariable and multivariable logistic regressions were used to analyze the factors affecting patients receiving chemotherapy. Kaplan-Meier (K-M) curve was used to analyze the survival benefit of chemotherapy in patients with osteosarcoma. Finally, we used annual percentage change (APC) to evaluate the annual changes in chemotherapy treatment rates and trends in 5-year survival rates in osteosarcoma patients. RESULTS: A total of 2157 osteosarcoma patients were included, of which 1887 patients received chemotherapy. Factors affecting patients receiving chemotherapy included age, primary tumor site, tumor size, N stage, M stage, and surgery. The K-M curve showed that older patients could benefit significantly from chemotherapy. The APC results showed no significant change in the chemotherapy treatment rate and 5-year overall survival rate of osteosarcoma patients. CONCLUSION: Chemotherapy is an irreplaceable treatment for patients with osteosarcoma. However, in recent years, there has been no significant progress in chemotherapy for osteosarcoma, and the long-term survival of patients has not improved significantly. New chemotherapeutic drugs or drug delivery systems are urgently needed to improve the prognosis of patients with osteosarcoma.

Development of a Machine Learning-Based Prediction Model for Chemotherapy-Induced Myelosuppression in Children with Wilms' Tumor.

Purpose: Develop and validate an accessible prediction model using machine learning (ML) to predict the risk of chemotherapy-induced myelosuppression (CIM) in children with Wilms' tumor (WT) before chemotherapy is administered, enabling early preventive management. Methods: A total of 1433 chemotherapy cycles in 437 children with WT who received chemotherapy in our hospital from January 2009 to March 2022 were retrospectively analyzed. Demographic data, clinicopathological characteristics, hematology and blood biochemistry baseline results, and medication information were collected. Six ML algorithms were used to construct prediction models, and the predictive efficacy of these models was evaluated to select the best model to predict the risk of grade ≥ 2 CIM in children with WT. A series of methods, such as the area under the receiver operating characteristic curve (AUROC), the calibration curve, and the decision curve analysis (DCA) were used to test the model's accuracy, discrimination, and clinical practicability. Results: Grade ≥ 2 CIM occurred in 58.5% (839/1433) of chemotherapy cycles. Based on the results of the training and validation cohorts, we finally identified that the extreme gradient boosting (XGB) model has the best predictive efficiency and stability, with an AUROC of up to 0.981 in the training set and up to 0.896 in the test set. In addition, the calibration curve and the DCA showed that the XGB model had the best discrimination and clinical practicability. The variables were ranked according to the feature importance, and the five variables contributing the most to the model were hemoglobin (Hgb), white blood cell count (WBC), alkaline phosphatase, coadministration of highly toxic chemotherapy drugs, and albumin. Conclusions: The incidence of grade ≥ 2 CIM was not low in children with WT, which needs attention. The XGB model was developed to predict the risk of grade ≥ 2 CIM in children with WT for the first time. The model has good predictive performance and stability and has the potential to be translated into clinical applications. Based on this modeling and application approach, the extension of CIM prediction models to other pediatric malignancies could be expected.

BI-D1870 Induces Mitotic Dysfunction and Apoptosis in Neuroblastoma by Regulating the PI3K-Akt-mTORC1 Signal Axis.

Introduction: Neuroblastoma (NB) is one of the most common extracranial solid malignant tumors in children. The 5-year survival rate of high-risk or refractory NB is less than 50%. Therefore, developing new effective therapeutics for NB remains an urgent challenge. Materials and Methods: Based on the NB dataset TARGET-NBL in the TCGA database, the prognosis-related genes were analyzed using univariate cox regression (p < 0.01). The protein network interaction of prognostic genes was analyzed using STRING to obtain 150 hub genes with HR > 1 and 150 hub genes with HR < 1. The Connectivity Map database was used to predict a therapeutic drug: BI-D1870, a ribosomal S6 kinase inhibitor. The inhibitory effect of BI-D1870 on NB was investigated through in vivo and in vitro experiments, and its inhibitory mechanism was explored. Results: Both the in vivo and in vitro experiments showed that BI-D1870 could inhibit tumor proliferation and induce tumor apoptosis. Furthermore, we proved that BI-D1870 caused G2/M phase arrest and mitosis damage in cells. RNA-seq of cells showed that BI-D1870 may inhibit the growth of NB by inhibiting the PI3K-Akt-mTOR axis. Western blot and immunofluorescence testing showed that BI-D1870 inhibited the PI3K-Akt-mTORC1 signal pathway to regulate the phosphorylation of RPS6 and 4E BP1 proteins, inhibit protein translation, and inhibit microtubule formation, thus preventing mitotic proliferation and inducing apoptosis. Conclusions: This study provides strong support that BI-D1870 may be a potential adjuvant therapy for NB.

The PI3K-AKT-mTOR signaling pathway mediates the cytoskeletal remodeling and epithelial-mesenchymal transition in bladder outlet obstruction.

Objective: Partial bladder outlet obstruction(pBOO) is the most common cause of lower urinary tract symptoms (LUTS) and significantly affects the quality of life. Long-term pBOO can cause changes in bladder structure and function, referred to as bladder remodeling. The pathogenesis of pBOO-induced bladder remodeling has yet to be fully understood, so effective treatment options are lacking. Our study aimed to explore how pBOO-induced bladder remodeling brings new strategies for treating pBOO. Methods: A rat model of pBOO was established by partial ligation of the bladder neck, and the morphological changes and fibrosis changes in the bladder tissues were detected by H&E and Masson trichrome staining. Furthermore, EMT(epithelial-mesenchymal transition) related indicators and related pathway changes were further examined after TGF- ß treatment of urothelial cells SV-HUC-1. Finally, the above indicators were tested again after using the PI3K inhibitor. Subsequently, RNA sequencing of bladder tissues to identify differential genes and related pathways enrichment and validated by immunofluorescence and western blotting analysis. Results: The pBOO animal model was successfully established by partially ligating the bladder neck. H&E staining showed significant changes in the bladder structure, and Masson trichrome staining showed significantly increased collagen fibers. RNA sequencing results significantly enriched in the cytoskeleton, epithelial-mesenchymal transformation, and the PI3K-AKT-mTOR signaling pathway. Immunofluorescence and western blotting revealed EMT and cytoskeletal remodeling in SV-HUC-1 cells after induction of TGF- ß and in the pBOO bladder tissues. The western blotting showed significant activation of the PI3K-AKT-mTOR signaling pathway in SV-HUC-1 cells after induction of TGF-ß and in pBOO bladder tissues. Furthermore, EMT and cytoskeletal damage were partially reversed after PI3K pathway inhibition using PI3K inhibitors. Conclusions: In the pBOO rat model, the activation of the PI3K-AKT-mTOR signaling pathway can mediate the cytoskeletal remodeling and the EMT to induce fibrosis in the bladder tissues. PI3K inhibitors partially reversed EMT and cytoskeletal damage.

Activation of the p53 signaling pathway by piRNA-MW557525 overexpression induces a G0/G1 phase arrest thus inhibiting neuroblastoma growth.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children. Due to drug resistance to radiotherapy and chemotherapy, mainly due to the existence of cancer stem cells (CSCs), some children still have a poor prognosis. Therefore, researchers have focused their attention on CSCs. Our research group successfully constructed cancer stem cell-like cells named Piwil2-iCSCs by reprogramming human preputial fibroblasts (FBs) with the PIWIL2 gene in the early stage, and Piwil2-iCSCs were confirmed to induce the formation of embryonic tumors. PiRNAs, noncoding small RNAs that interact with PIWI proteins, play important roles in a variety of tumors. Therefore, our study aimed to explore the role of differentially expressed (DE) piRNAs derived from sequencing of Piwil2-iCSCs in NB. METHODS: The DE piRNAs in Piwil2-iCSCs were screened using high-throughput sequencing and further verified in NB tissues and cells. An unknown piRNA, named piRNA-MW557525, showed obvious downregulation in NB. Thus we studied the effect of piRNA-MW557525 on the biological behavior of NB through in vitro and in vivo experiments. On this basis, we successfully constructed a stably transfected NB cell line overexpressing piRNA-MW557525 and performed transcriptome sequencing to further explore the mechanism of piRNA-MW557525 in NB. RESULTS: In vitro, piRNA-MW557525 inhibited NB cell proliferation, migration and invasion and induced apoptosis; in vivo, piRNA-MW557525 significantly reduced the volume and weight of tumors and inhibited their proliferation, migration and invasion. piRNA-MW557525 overexpression induced G0/G1 phase arrest in NB cells via activation of the P53-P21-CDK2-Cyclin E signaling pathway thus inhibiting NB growth. CONCLUSIONS: Our findings show that piRNA-MW557525 functions as a tumor suppressor gene in NB and may serve as an innovative biomarker and possible therapeutic target for NB.

BKM120 inhibits malignant rhabdoid tumor of the kidney through induction of apoptosis and G0/G1 phase arrest.

Malignant rhabdoid tumor of the kidney (MRTK) has an inferior prognosis and is insensitive to radiotherapy and chemotherapy. Search for novel, potent medicinal agents is urgent. Herein, data on the gene expression and clinical characteristics of malignant rhabdoid tumors (MRT) were retrieved from the TARGET database. Prognosis-related genes were identified by differential analysis and one-way cox regression analysis, and prognosis-related signalling pathways were identified by enrichment analysis. The prognosis-related genes were imported into the Connectivity Map database for query, and BKM120 was predicted and screened as a potential therapeutic agent for MRTK. A combination of high-throughput RNA sequencing and Western blot verified that the PI3K/Akt signaling pathway is associated with MRTK prognosis and is overactivated in MRTK. Our results outlined that BKM120 inhibited the proliferation, migration, and invasion ability of G401 cells and induced apoptosis and cell cycle G0/G1 phase arrest. In vivo, BKM120 inhibited tumor growth and had no significant toxic side effects. Western blot and immunofluorescence results confirmed that BKM120 could reduce the expression of PI3K and p-AKT, critical proteins of the PI3K/Akt signaling pathway. BKM120 inhibits MRTK by inhibiting PI3K/Akt signalling pathway to induce apoptosis and cell cycle G0/G1 phase arrest, which is anticipated to give the clinical treatment of MRTK a new direction.

Development of a loop-mediated isothermal amplification assay for detection of Cronobacter spp. (Enterobacter sakazakii).

Contamination of Cronobacter spp. (Enterobacter sakazakii) in infant formulas and other food products is a severe problem. Here a loop-mediated isothermal amplification (LAMP) assay was developed for rapidly detecting Cronobacter spp. in powdered infant formula. Sequences of 16S/23S rDNA internal intergenic spacer of Cronobacter spp. were used as the target template to design LAMP primers. The detection outcome can be evaluated by the white precipitate or the fluorescence intensity under ultraviolet irradiation, both visible to naked eyes. The sensitivity and specificity of the LAMP assay was further analyzed in comparison with that of regular PCR and real time quantitative PCR. The results showed that all of Cronobacter spp. strains display positive reaction to the detections while all of the non-Cronobacter spp. strains were negative, and that the LAMP assay exhibits a high sensitivity of 9.1 fg/µL (The sensitivity of regular PCR and real time quantitative PCR is 91 and 9.1 pg/µL, respectively.). The amplified reaction could be accomplished in about 1 h, with the results visible to naked eyes. Hence, the LAMP assay developed by this study can provide a rapid and simple approach for the detection of Cronobacter spp. in infant formula.

A Nomogram for Predicting Cancer-Specific Survival in Children With Wilms Tumor: A Study Based on SEER Database and External Validation in China.

Background: Wilms tumor (WT) is the most common tumor in children. We aim to construct a nomogram to predict the cancer-specific survival (CSS) of WT in children and externally validate in China. Methods: We downloaded the clinicopathological data of children with WT from 2004 to 2018 in the SEER database. At the same time, we used the clinicopathological data collected previously for all children with WT between 2013 and 2018 at Children's Hospital of Chongqing Medical University (Chongqing, China). We analyzed the difference in survival between the patients in the SEER database and our hospital. Cox regression analysis was used to screen for significant risk factors. Based on these factors, a nomogram was constructed to predict the CSS of children with WT. Calibration curve, concordance index (C-index), the area under the receiver operating curve (AUC) and decision curve analysis (DCA) was used to evaluate the accuracy and reliability of the model. Results: We included 1,045 children with WT in the SEER database. At the same time, we collected 112 children with WT in our hospital. The Kaplan-Meier curve suggested that children in China with WT had a higher mortality rate than those in the United States. Cox regression analysis revealed that age, lymph node density (LND), and tumor stage were significant prognostic factors for the patients in the SEER database. However, the patients in our hospital only confirmed that the tumor stage and the number of positive regional lymph nodes were significant factors. The prediction model established by the SEER database had been validated internally and externally to prove that it had good accuracy and reliability. Conclusion: We have constructed a survival prognosis prediction model for children with WT, which has been validated internally and externally to prove accuracy and reliability.

DNA Hypermethylation-Regulated CX3CL1 Reducing T Cell Infiltration Indicates Poor Prognosis in Wilms Tumour.

Objective: To investigate the role of chemokines in Wilms tumours, especially their chemotaxis to immune cells and the role of DNA methylation in regulating the expression level of chemokines. Methods: RNAseqV2 gene expression and clinical data were downloaded from the TARGET database. DNA methylation data were downloaded from the GEO and cBioPortal database. The difference analysis and Kaplan-Meier(KM) analysis of chemokines were performed by edgeR package. Then predictive model based on chemokines was constructed by lasso regression and multivariate COX regression. ROC curve, DCA curve, Calibration curve, and Nomogram were used to evaluate the prognostic model. MCPcounter and Cibersort algorithm was used to calculate the infiltration of immune cells in Wilms tumour and para-tumour samples. Then the difference analysis of the immune cells was performed. The relationship between chemokines and immune cells were calculated by Pearson correlation. In addition, DNA methylation differences between Wilms tumour and para-tumour samples was performed. The correlation between DNA methylation and mRNA expression was calculated by Pearson correlation. Western blot(WB)and immunofluorescence were used to confirm the differential expression of CX3CL1 and T cells, and the correlation between them. Results: A total of 16 chemokines were differentially expressed in tumour and para-tumour samples. A total of seven chemokines were associated with survival. CCL2 and CX3CL1 were positively correlated with prognosis, while high expression of CCL3, CCL8, CCL15, CCL18 and CXCL9 predicted poor prognosis. By lasso regression and multivariate COX regression, CCL3, CCL15, CXCL9 and CX3CL1 were finally included to construct a prediction model. The model shows good prediction ability. MCPcounter and Cibersort algorithm both showed that T cells were higher in para-tumour tissues than cancer tissues. Correlation analysis showed that CX3CL1 had a strong correlation with T cells. These were verified by Weston blot and immunofluorescence. DNA methylation analysis showed that various chemokines were different in para-tumours and tumours. CX3CL1 was hypermethylated in tumours, and the degree of methylation was negatively correlated with mRNA expression. Conclusion: 1. There is low T cell infiltration in nephroblastoma. 2. Chemokines such as CX3CL1 indicate a favourable prognosis and positively correlate with the number of T cells. 3. chemokines such as CX3CL1 are negatively regulated by DNA hypermethylation.

Development and Validation of a Competitive Risk Model in Elderly Patients With Chromophobe Cell Renal Carcinoma: A Population-Based Study.

Background: Renal cell carcinoma (RCC) is the most common renal malignancy in adults, and chromophobe renal cell carcinoma (chRCC) is the third most common subtype of RCC. We aimed to construct a competitive risk model to predict cancer-specific survival (CSS) in elderly patients with chRCC. Methods: The clinicopathological information of the patients was downloaded from the SEER database, and the patients were randomly divided into the training and validation cohorts. Patients' risk factors for cancer-specific death (CSM) were analyzed using proportional subdistribution hazard (SH). We constructed a competitive risk model to predict the CSS of elderly chRCC patients. Consistency index (C-index), the area under receiver operating curve (AUC), and a calibration curve were used to validate the model's accuracy. Decision curve analysis (DCA) was used to test the clinical value of the model. Results: A total of 3,522 elderly patients with chRCC were included in the analysis. Patients were randomly assigned to either the training cohort (N = 2,474) or the validation cohort (N = 1,048). SH analysis found that age, race, T, N, and M stage, tumor size, and surgery were risk factors for CSM. We constructed a competitive risk model to predict patients' CSS. In the training set, the model predicted patients' 1-, 3-, and 5-year CSS with C-indices of 82.2, 80.8, and 78.2, respectively. The model predicted patient 1-, 3-, and 5-year CSS in the validation cohort with C-indices of 84.7, 83.4, and 76.9, respectively. The calibration curve showed that the model's predicted value is almost consistent with the observed value, which indicated that the model has good accuracy. The AUC of the training set and validation queue also suggested that the model has good discrimination. The clinical utility of the DCA model in predicting patients' CSS is higher than that of traditional TNM staging. Conclusions: We constructed a competitive risk model to predict CSS in elderly patients with chRCC. The model has good accuracy and reliability, which can help doctors and patients to make clinical decisions and follow-up strategies.

Development and Validation of Nomograms to Predict Cancer-Specific Survival and Overall Survival in Elderly Patients With Prostate Cancer: A Population-Based Study.

Objective: Prostate cancer (PC) is the most common non-cutaneous malignancy in men worldwide. Accurate predicting the survival of elderly PC patients can help reduce mortality in patients. We aimed to construct nomograms to predict cancer-specific survival (CSS) and overall survival (OS) in elderly PC patients. Methods: Information on PC patients aged 65 years and older was downloaded from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression models were used to determine independent risk factors for PC patients. Nomograms were developed to predict the CSS and OS of elderly PC patients based on a multivariate Cox regression model. The accuracy and discrimination of the prediction model were tested by the consistency index (C-index), the area under the subject operating characteristic curve (AUC), and the calibration curve. Decision curve analysis (DCA) was used to test the clinical value of the nomograms compared with the TNM staging system and D'Amico risk stratification system. Results: 135183 elderly PC patients in 2010-2018 were included. All patients were randomly assigned to the training set (N=94764) and the validation set (N=40419). Univariate and multivariate Cox regression model analysis revealed that age, race, marriage, histological grade, TNM stage, surgery, chemotherapy, radiotherapy, biopsy Gleason score (GS), and prostate-specific antigen (PSA) were independent risk factors for predicting CSS and OS in elderly patients with PC. The C-index of the training set and the validation set for predicting CSS was 0.883(95%CI:0.877-0.889) and 0.887(95%CI:0.877-0.897), respectively. The C-index of the training set and the validation set for predicting OS was 0.77(95%CI:0.766-0.774)and 0.767(95%CI:0.759-0.775), respectively. It showed that the proposed model has excellent discriminative ability. The AUC and the calibration curves also showed good accuracy and discriminability. The DCA showed that the nomograms for CSS and OS have good clinical potential value. Conclusions: We developed new nomograms to predict CSS and OS in elderly PC patients. The models have been internally validated with good accuracy and reliability and can help doctors and patients to make better clinical decisions.

Amputation Predisposes to Higher Cancer-Specific Mortality Than Limb Salvage Surgery in Pediatric Patients With Osteosarcoma of the Limbs: A Propensity Matching Analysis.

OBJECTIVE: With the development of osteosarcoma treatment, limb salvage surgery is gradually replacing amputation as the primary surgical option. Most pediatric osteosarcomas of the limbs undergo limb-salvage surgery. We aimed to use propensity score matching (PSM) analysis test the difference in cancer-specific mortality (CSM) between amputation and limb-salvage surgery in pediatric patients with Osteosarcoma of the limbs. PSM is a statistical method used to deal with data from an Observational Study. The PSM method is designed to reduce the influence of biases and confounding variables to make a more reasonable comparison between experimental and control groups. METHODS: Patient information was downloaded from the SEER (surveillance, epidemiology, and End Results) database from 2004 to 2018. We included all primary pediatric osteosarcoma patients who underwent limb salvage or amputation. Multivariate logistic regression models were used to explore the factors influencing patient choice of amputation. Differences in CSM and other causes of mortality (OSM) between limb salvage and amputation were analyzed using cumulative incidence plots and competitive risk regression tests after 1:1 proportional propensity score matching. RESULTS: A total of 1,058 pediatric patients with limbs Osteosarcoma were included. Patients who underwent amputations were more likely to be male (OR 1.4, P = 0.024) and more likely to have distant metastasis (OR 2.1, P < 0.001). Before propensity matching, CSM was 1.4 times higher in patients undergoing amputation than in patients undergoing limb salvage (P = 0.017) and 3.4 times higher in OSM (P = 0.007). After adjustment for propensity matching, CSM was 1.5 times higher in patients undergoing amputation than in patients undergoing limb salvage (P = 0.028), but there was no significant difference in OSM (HR 3.2, P = 0.078). CONCLUSIONS: Our results suggested that amputation is associated with a 1.5-fold increase in CSM in pediatric patients with limbs Osteosarcoma. Therefore, in the surgical selection of pediatric patients with Osteosarcoma, limb salvage surgery should be the first choice in the absence of other contraindications.

A Nomogram for Predicting Cancer-Specific Survival of Osteosarcoma and Ewing's Sarcoma in Children: A SEER Database Analysis.

BACKGROUND: Osteosarcoma (OSC) and Ewing's sarcoma (EWS) are children's most common primary bone tumors. The purpose of the study is to develop and validate a new nomogram to predict the cancer-specific survival (CSS) of childhood OSC and EWS. METHODS: The clinicopathological information of all children with OSC and EWS from 2004 to 2018 was downloaded from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analyses were used to screen children's independent risk factors for CSS. These risk factors were used to construct a nomogram to predict the CSS of children with OSC and EWS. A series of validation methods, including calibration plots, consistency index (C-index), and area under the receiver operating characteristic curve (AUC), were used to validate the accuracy and reliability of the prediction model. Decision curve analysis (DCA) was used to validate the clinical application efficacy of predictive models. All patients were divided into low- and high-risk groups based on the nomogram score. Kaplan-Meier curve and log-rank test were used to compare survival differences between the two groups. RESULTS: A total of 2059 children with OSC and EWS were included. All patients were randomly divided into training cohort 60% (N = 1215) and validation cohort 40% (N = 844). Univariate and multivariate analysis suggested that age, surgery, stage, primary site, tumor size, and histological type were independent risk factors. Nomograms were established based on these factors to predict 3-, 5-, and 8-years CSS of children with OSC and EWS. The calibration plots showed that the predicted value was highly consistent with the actual value. In the training cohort and validation cohort, the C-index was 0.729 (0.702-0.756) and 0.735 (0.702-0.768), respectively. The AUC of the training cohort and the validation cohort also showed similar results. The DCA showed that the nomogram had good clinical value. CONCLUSION: We constructed a new nomogram to predict the CSS of OSC and EWS in children. This predictive model has good accuracy and reliability and can help doctors and patients develop clinical strategies.

Doxycycline Hydrochloride Regulates Cytoskeletal Rearrangement and Epithelial-To-Mesenchymal Transition in Malignant Rhabdoid Tumour of the Kidney.

Objective: As a highly malignant tumour, malignant rhabdoid tumours of the kidney (MRTK) are prone to metastasis and invasion, while tumour metastasis and invasion are inseparable from matrix metalloproteinases (MMPs) and epithelial-mesenchymal transformation (EMT). Moreover, the key to EMT is remodelling of the cytoskeleton. Therefore, our study is aimed at investigating whether doxycycline hydrochloride (DCH), an inhibitor of MMPs, could reverse EMT in MRTK to exert an antitumour effect by regulating MMPs and the cytoskeleton. Methods: The existence of EMT in MRTK cells was verified by bioinformatics analysis, immunofluorescence, and western blotting (WB). In vitro, the proliferation, migration, and invasion abilities of G401 cells were examined by Cell Counting Kit-8 (CCK-8), scratch, and Transwell assays, respectively. The effect of DCH on tumour growth in tumour-bearing mice was explored in in vivo experiments, and the expression of MMP2 and MMP9 and EMT correlation indexes was measured by immunofluorescence and WB, and the changes in cytoskeletal F-actin and ß-tubulin were measured by fluorescence. Results: The altered extracellular matrix (ECM) composition, EMT, and high expression of MMP2 and MMP9 existed in MRTK. DCH inhibited the proliferation, migration, and invasion of G401 cells in vitro. In vivo, DCH inhibited tumour growth in mice, downregulated the expression of MMP2 and MMP9, and partially reversed EMT. Alternatively, DCH resulted in cytoskeletal rearrangements of G401 cells. Conclusions: DCH, as an MMP inhibitor, is used for the first time in MRTK research, showing good antitumour effects by reversing EMT and potentially providing new therapeutic measures for MRTK treatment.