Identification of bladder cancer subtypes and predictive signature for prognosis, immune features, and immunotherapy based on immune checkpoint genes.

Immunotherapy based on immune checkpoint genes (ICGs) has recently made significant progress in the treatment of bladder cancer patients, but many patients still cannot benefit from it. In the present study, we aimed to perform a comprehensive analysis of ICGs in bladder cancer tissues with the aim of evaluating patient responsiveness to immunotherapy and prognosis. We scored ICGs in each BLCA patient from TCGA and GEO databases by using ssGSEA and selected genes that were significantly associated with ICGs scores by using the WCGNA algorithm. NMF clustering analysis was performed to identify different bladder cancer molecular subtypes based on the expression of ICGs-related genes. Based on the immune related genes differentially expressed among subgroups, we further constructed a novel stratified model containing nine genes by uni-COX regression, LASSO regression, SVM algorithm and multi-COX regression. The model and the nomogram constructed based on the model can accurately predict the prognosis of bladder cancer patients. Besides, the patients classified based on this model have large differences in sensitivity to immunotherapy and chemotherapy, which can provide a reference for individualized treatment of bladder cancer.

Role of ferroptosis in fibrosis: From mechanism to potential therapy.

ABSTRACT: Fibrosis, which is a manifestation of the physiological response to injury characterized by excessive accumulation of extracellular matrix components, is a ubiquitous outcome of the repair process. However, in cases of repetitive or severe injury, fibrosis may become dysregulated, leading to a pathological state and organ failure. In recent years, a novel form of regulated cell death, referred to as ferroptosis, has been identified as a possible contributor to fibrosis; it is characterized by iron-mediated lipid peroxidation. It has garnered attention due to the growing body of evidence linking ferroptosis and fibrogenesis, which is believed to be driven by underlying inflammation and immune responses. Despite the increasing interest in the relationship between ferroptosis and fibrosis, a comprehensive understanding of the precise role that ferroptosis plays in the formation of fibrotic tissue remains limited. This review seeks to synthesize previous research related to the topic. We categorized the different direct and indirect mechanisms by which ferroptosis may contribute to fibrosis into three categories: (1) iron overload toxicity; (2) ferroptosis-evoked necroinflammation, with a focus on ferroptosis and macrophage interplay; and (3) ferroptosis-associated pro-fibrotic factors and pathways. Furthermore, the review considers the potential implications of these findings and highlights the utilization of ferroptosis-targeted therapies as a promising strategy for mitigating the progression of fibrosis. In conclusion, novel anti-fibrotic treatments targeting ferroptosis could be an effective treatment for fibrosis.

Identification of potential necroinflammation-associated necroptosis-related biomarkers for delayed graft function and renal allograft failure: a machine learning-based exploration in the framework of predictive, preventive, and personalized medicine.

Delayed graft function (DGF) is one of the key post-operative challenges for a subset of kidney transplantation (KTx) patients. Graft survival is significantly lower in recipients who have experienced DGF than in those who have not. Assessing the risk of chronic graft injury, predicting graft rejection, providing personalized treatment, and improving graft survival are major strategies for predictive, preventive, and personalized medicine (PPPM/3PM) to promote the development of transplant medicine. However, since PPPM aims to accurately identify disease by integrating multiple omics, current methods to predict DGF and graft survival can still be improved. Renal ischemia/reperfusion injury (IRI) is a pathological process experienced by all KTx recipients that can result in varying occurrences of DGF, chronic rejection, and allograft failure depending on its severity. During this process, a necroinflammation-mediated necroptosis-dependent secondary wave of cell death significantly contributes to post-IRI tubular cell loss. In this article, we obtained the expression matrices and corresponding clinical data from the GEO database. Subsequently, nine differentially expressed necroinflammation-associated necroptosis-related genes (NiNRGs) were identified by correlation and differential expression analysis. The subtyping of post-KTx IRI samples relied on consensus clustering; the grouping of prognostic risks and the construction of predictive models for DGF (the area under the receiver operating characteristic curve (AUC) of the internal validation set and the external validation set were 0.730 and 0.773, respectively) and expected graft survival after a biopsy (the internal validation set's 1-year AUC: 0.770; 2-year AUC: 0.702; and 3-year AUC: 0.735) were based on the least absolute shrinkage and selection operator regression algorithms. The results of the immune infiltration analysis showed a higher infiltration abundance of myeloid immune cells, especially neutrophils, macrophages, and dendritic cells, in the cluster A subtype and prognostic high-risk groups. Therefore, in the framework of PPPM, this work provides a comprehensive exploration of the early expression landscape, related pathways, immune features, and prognostic impact of NiNRGs in post-KTx patients and assesses their capabilities as.predictors of post-KTx DGF and graft loss,targets of the vicious loop between regulated tubular cell necrosis and necroinflammation for targeted secondary and tertiary prevention, andreferences for personalized immunotherapy. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00320-w.

Perfusate Neutrophil Gelatinase-Associated Lipocalin, Kidney Injury Molecular-1, Liver-Type Fatty Acid Binding Protein, and Interleukin-18 as Potential Biomarkers to Predict Delayed Graft Function and Long-Term Prognosis in Kidney Transplant Recipients: A Single-Center Retrospective Study.

BACKGROUND Delayed graft function (DGF) caused by ischemia-reperfusion injury is a common pathophysiological process that should be monitored by specific biomarkers in addition to serum creatinine. Thus, this single-center retrospective study aimed to investigate the association between levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecular-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), and interleukin-18 (IL-18) in DGF associated with acute kidney injury in kidney transplant recipients (KTRs) and estimated glomerular filtration rate (eGFR) at 3 years post-transplant. MATERIAL AND METHODS A total of 102 KTRs [14(13.7%) of DGF and 88(86.3%) of NON-DGF] were enrolled. DGF was defined as "dialysis is needed within 1 week after kidney transplantation". NGAL, KIM-1, L-FABP, and IL-18 were obtained from perfusate samples of donation-after-cardiac-death (DCD) kidneys, and measured by ELISA. RESULTS Compared to the NON-DGF group, KTRs in the DGF group had a statistically significant increase in levels of NGAL (P<0.001) and KIM-1 (P<0.001). Multiple logistic regression analyses showed that NGAL (OR=1.204, 95% CI 1.057-1.372, P=0.005) and KIM-1 (OR=1.248, CI=1.065-1.463, P=0.006) could be regarded as independent risk factors. The accuracy of NGAL and KIM-1 was 83.3% and 82.1%, respectively, calculated using the area under the receiver operating characteristic curve. Furthermore, the eGFR at 3 years post-transplant had a moderate negative correlation with NGAL (r=-0.208, P=0.036) and KIM-1 (r=-0.260, P=0.008). CONCLUSIONS Our results support those from previous studies showing that perfusate levels of NGAL and KIM-1 are associated with DGF in KTRs and also with reduced eGFR at 3 years post-transplant.

STEAP3 can predict the prognosis and shape the tumor microenvironment of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urinary system characterized by poor prognosis and difficult treatment. It has been reported that iron metabolism dysregulation is a common phenomenon in ccRCC and is closely related to the process of ccRCC. But still now, the exact function and underlying mechanisms of iron metabolism dysregulation in ccRCC have not been fully elucidated. In this study, we comprehensively investigated the prognostic value and potential role of STEAP3 (an iron metabolism-related gene) in ccRCC. STEAP3 is significantly up-regulated in ccRCC. High STEAP3 expression is associated with gender, hemoglobin level, pathological grade, tumor stage and significantly predicts an unfavorable prognosis of ccRCC patients. Functional enrichment analysis and evaluation of the tumor microenvironment indicated that STEAP3 was involved in the remodeling of tumor extracellular matrix and the shaping of an immune-suppressive tumor microenvironment to promote tumor metastasis and evade immune killing. Besides, the expression of STEAP3 is also associated with the expression of various immune checkpoint molecules and the IC50 of targeted drugs. Finally, we verified STEAP3 by RT-qPCR and IHC staining. In conclusion, we found that STEAP3 can serve as a candidate prognostic biomarker for ccRCC, and targeting STEAP3 and its biological processes may provide new references for the individualized treatment of ccRCC.

The role of extracellular traps in ischemia reperfusion injury.

In response to strong signals, several types of immune cells release extracellular traps (ETs), which are web-like structures consisting of DNA decorated with various protein substances. This process is most commonly observed in neutrophils. Over the past two decades, ET formation has been recognized as a unique mechanism of host defense and pathogen destruction. However, the role of ETs in sterile inflammation has only been studied extensively in recent years. Ischemia reperfusion injury (IRI) is a type of sterile inflammatory injury. Several studies have reported that ETs have an important role in IRI in various organs. In this review, we describe the release of ETs by various types of immune cells and focus on the mechanism underlying the formation of neutrophil ETs (NETs). In addition, we summarize the role of ETs in IRI in different organs and their effects on tumors. Finally, we discuss the value of ETs as a potential therapeutic target for organ IRI and present possible challenges in conducting studies on IRI-related ETs as well as future research directions and prospects.

TGF-ß Enhances Immunosuppression of Myeloid-Derived Suppressor Cells to Induce Transplant Immune Tolerance Through Affecting Arg-1 Expression.

Myeloid-derived suppressor cells (MDSCs) are a class of heterogeneous myeloid cells, which play an important role in immunosuppression. We intended to find an effective method that can produce MDSCs with significantly better efficiency and promote immune tolerance for transplant rejection through cell therapy. It has been reported that granulocyte and macrophage colony-stimulating factor (GM-CSF) could induce MDSCs in vitro to cause immunosuppression. In the present study, transforming growth factor ß (TGF-ß) was added to the induction system, and flow cytometry analysis was used to detect the phenotypes of induced MDSCs. Their potential immunosuppressive function and mechanisms were determined by co-culturing MDSCs with stimulated T cells in vitro and transferring MDSCs to the skin grafted C57BL/6J mouse models in vivo. It was found that the addition of TGF-ß could effectively cause bone marrow cells to differentiate into a group of cells with stronger immunosuppressive functions, thereby inhibiting the proliferation of stimulated T cells. The population of CD11b+Gr-1+ MDSCs also increased significantly as compared with GM-CSF alone treatment. While detecting for immunosuppressive effectors, we found that expression of arginase 1 (Arg-1) was significantly upregulated in these MDSCs, and inhibitor of Arg-1 significantly suppressed their immunosuppressive capabilities. Moreover, an adoptive transfer of these cells significantly prolonged survival of allo-skin and improved immune tolerance in vivo. These findings indicated that TGF-ß + GM-CSF could serve as an effective and feasible method to induce powerful immunosuppressive MDSCs in vitro. Thus, TGF-ß + GM-CSF-induced MDSCs may have a promising role in prevention of the graft rejection.

Metastatic Clear Cell Renal Cell Carcinoma to Pancreas and Distant Organs 24 Years After Radical Nephrectomy: A Case Report and Literature Review.

Background: Clear cell renal cell carcinoma (CCRCC) is a common urological neoplasm, and even though surgical resection is effective for localized CCRCC, the prognosis of metastatic CCRCC is poor. Currently, there is a paucity of recognized effective therapeutic protocols for metastatic CCRCC. Case presentation: A 76-year-old Asian man underwent radical left nephrectomy for CCRCC 26 years ago; this patient visited our hospital with abdominal pain due to multiple abdominal metastases 24 years after the nephrectomy. After metastasectomy, he underwent targeted therapy combined with a programmed death receptor-1 (PD-1) inhibitor, and the current imaging results indicate remarkable tumor remission. Conclusions: Metachronous pancreatic metastasis from CCRCC after nephrectomy is rare, but clinicians and patients should not ignore this possibility. The combination of targeted therapy and immunotherapy can result in satisfactory outcomes in cases where metastatic CCRCC continues to progress despite metastasectomy and targeted therapy. The combination of local and systemic therapy can be an effective therapeutic protocol for metastatic CCRCC, but there is no consensus on suitable therapeutics.

Tumor-Associated Inflammation: The Tumor-Promoting Immunity in the Early Stages of Tumorigenesis.

Tumorigenesis is a multistage progressive oncogenic process caused by alterations in the structure and expression level of multiple genes. Normal cells are continuously endowed with new capabilities in this evolution, leading to subsequent tumor formation. Immune cells are the most important components of inflammation, which is closely associated with tumorigenesis. There is a broad consensus in cancer research that inflammation and immune response facilitate tumor progression, infiltration, and metastasis via different mechanisms; however, their protumor effects are equally important in tumorigenesis at earlier stages. Previous studies have demonstrated that during the early stages of tumorigenesis, certain immune cells can promote the formation and proliferation of premalignant cells by inducing DNA damage and repair inhibition, releasing trophic/supporting signals, promoting immune escape, and activating inflammasomes, as well as enhance the characteristics of cancer stem cells. In this review, we focus on the potential mechanisms by which immune cells can promote tumor initiation and promotion in the early stages of tumorigenesis; furthermore, we discuss the interaction of the inflammatory environment and protumor immune cells with premalignant cells and cancer stem cells, as well as the possibility of early intervention in tumor formation by targeting these cellular mechanisms.

A promising Prognostic risk model for advanced renal cell carcinoma (RCC) with immune-related genes.

BACKGROUND: Renal cell carcinoma (RCC) is a third most common tumor of the urinary system. Nowadays, Immunotherapy is a hot topic in the treatment of solid tumors, especially for those tumors with pre-activated immune state. METHODS: In this study, we downloaded genomic and clinical data of RCC samples from The Cancer Genome Atlas (TCGA) database. Four immune-related genetic signatures were used to predict the prognosis of RCC by Cox regression analysis. Then we established a prognostic risk model consisting of the genes most related to prognosis from four signatures to value prognosis of the RCC samples via Kaplan-Meier (KM) survival analysis. An independent data from International Cancer Genome Consortium (ICGC) database were used to test the predictive stability of the model. Furthermore, we performed landscape analysis to assess the difference of gene mutant in the RCC samples from TCGA. Finally, we explored the correlation between the selected genes and the level of tumor immune infiltration via Tumor Immune Estimation Resource (TIMER) platform. RESULTS: We used four genetic signatures to construct prognostic risk models respectively and found that each of the models could divide the RCC samples into high- and low-risk groups with significantly different prognosis, especially in advanced RCC. A comprehensive prognostic risk model was constructed by 8 candidate genes from four signatures (HLA-B, HLA-A, HLA-DRA, IDO1, TAGAP, CIITA, PRF1 and CD8B) dividing the advanced RCC samples from TCGA database into high-risk and low-risk groups with a significant difference in cancer-specific survival (CSS). The stability of the model was verified by independent data from ICGC database. And the classification efficiency of the model was stable for the samples from different subgroups. Landscape analysis showed that mutation ratios of some genes were different between two risk groups. In addition, the expression levels of the selected genes were significantly correlated with the infiltration degree of immune cells in the advanced RCC. CONCLUSIONS: Sum up, eight immune-related genes were screened in our study to construct prognostic risk model with great predictive value for the prognosis of advanced RCC, and the genes were associated with infiltrating immune cells in tumors which have potential to conduct personalized treatment for advanced RCC.

Ferroptosis-Mediated Formation of Tumor-Promoting Immune Microenvironment.

Ferroptosis is a newly proposed programmed cell death that has great potential in limiting tumor progression and malignancies that are resistant to conventional therapies. However, recent reports have shown that ferroptosis in the tumor microenvironment can provide a favorable environment to promote tumor survival and progression, which is induced by the infiltration and polarization of pro-tumor immune cells and the dysfunction of anti-tumor immunity. In this mini-review, we introduce the mechanisms of ferroptosis, describe the crosstalk between ferroptosis and cancer, demonstrate the potential ways in which ferroptosis shapes the pro-tumor immune microenvironment, and present our thoughts on ferroptosis-based cancer therapies.

A Ferroptosis-Related Genes Model Allows for Prognosis and Treatment Stratification of Clear Cell Renal Cell Carcinoma: A Bioinformatics Analysis and Experimental Verification.

INTRODUCTION: Clear cell renal cell carcinoma (ccRCC) is a malignant tumor characterized by poor prognosis and difficult treatment. Ferroptosis is a relatively new form of programmed cell death that involved in cancer development and therapy resistance. Studies have shown that targeted ferroptosis may be a novel option for the treatment of ccRCC, but key genes and their roles between ferroptosis and ccRCC are limited so far. This study aims to develop a ccRCC stratified model based on ferroptosis-related genes to provide a reference for the prognosis prediction and the individualized treatment of ccRCC. MATERIALS AND METHODS: The mRNAs expression data of ccRCC and FRGs were obtained from TCGA and FerrDb database, respectively. Through multiple analysis, a 4-FRG based prognostic stratified model was constructed and its predictive performance was validated through various methods. Then, a nomogram based on the model was constructed and ccRCC patients stratified by the model were analyzed for tumor microenvironment, immune infiltration, sensitivity for immune checkpoint inhibitors (ICIs)/traditional anti-tumor therapy and tumor mutation burden (TMB). Functional enrichment analysis was performed to explore potential biological pathways. Finally, we verified our model by RT-qPCR, siRNA transfection, scratch assay and CCK-8 assay. RESULTS: In this study, the stratified model and a model-based nomogram can accurately predict the prognosis of ccRCC patients in TCGA database. The patients stratified by the model showed different tumor microenvironments, immune infiltration, TMB, resistance to traditional and ICIs therapy, and sensitivity to ferroptosis. Functional enrichment analysis suggested several biological pathways related to the process and prognosis of ccRCC. RT-qPCR confirmed the differential expression of ferroptosis-related genes. Scratch assay and CCK-8 assay indicated the promotion effects of CD44 on the proliferation and migration of ccRCC. CONCLUSION: In this study, we established a novel ccRCC stratified model based on FRGs, which can accurately predict the prognosis of ccRCC patients and provide a reference for clinical individualized treatment.

Nephrogenic adenoma of the renal pelvis: A rare case report and review of the literature.

RATIONALE: Nephrogenic adenoma (NA) is a rare benign lesion of the urinary tract, which rarely occurs in the renal pelvis. Only 19 cases have been reported in the literature. However, there is no detailed report on the clinicopathological features of NA of the renal pelvis. PATIENT CONCERNS: This case report describes a 46-year-old male patient who was admitted to the hospital for one month because of painless gross hematuria with blood clots. He had a history of hyperuricemia and a family history of gastric cancer. DIAGNOSES: NA of the renal pelvis was diagnosed pathologically and immunohistochemical. INTERVENTIONS: The patient underwent laparoscopic nephroureterectomy. OUTCOMES: The patient recovered well after the operation with no discomfort. In addition, we followed up with the patient regularly post-discharge (approximately 20 months). There were no obvious abnormalities in the results of routine urine culture, computed tomography scan of the abdomen, and cystoscopy during the follow-up period, and the symptoms disappeared completely and did not recur. LESSONS: NA of the renal pelvis is extremely rare in the clinic, which can be easily misdiagnosed and overtreated. However, for pathological diagnosis of this disease, specific immunohistochemical staining for preoperative biopsy was reported to be significant, which should be considered by the urologists and pathologists.

A Novel miRNA-Based Model Can Predict the Prognosis of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal malignant cancer, whose survival rate and quality of life of patients are still not satisfactory. Nevertheless, the TNM staging system currently used in clinical cannot make accurate survival predictions and precise treatment decisions for ccRCC patients. Therefore, there is an urgent need for more reliable biomarkers to identify high-risk subgroups of ccRCC patients to guide timely intervention and treatment. Recently, MiRNAs have been shown to be closely related to the procession of a variety of tumors, and they have high stability in various tissues, which makes them suggested to have the potential as a prognostic biomarker of ccRCC. In this study, by analyzing and processing the miRNAs expression profile of ccRCC patients from the TCGA database, we finally constructed an excellent miRNAs signature and verified it through a variety of methods. In order to build a more accurate and reliable clinical predictive model, we integrated the miRNAs signature with other prognostic-related clinical parameters to construct a nomogram. Functional enrichment analysis showed that miRNAs in the signature may regulate the genes involved in the Hippo signaling pathway, Tight junction, and Wnt signaling pathway to cause different prognoses of ccRCC patients, which may provide a reference for subsequent basic research and targeted therapy. To conclude, our study constructed a useful miRNAs signature, which allows the prognosis stratification for ccRCC patients and thereby guides the timely and effective interventions on high-risk patients. At the same time, this study also found the potential biological pathways involved in the procession of ccRCC.

A zinc finger protein gene signature enables bladder cancer treatment stratification.

Bladder cancer (BC) is a commonly occurring malignant tumor affecting the urinary tract. Zinc finger proteins (ZNFs) constitute the largest transcription factor family in the human genome and are therefore attractive biomarker candidates for BC prognosis. In this study, we profiled the expression of ZNFs in The Cancer Genome Atlas (TCGA) BC cohort and developed a novel prognostic signature based on 7 ZNF-coding genes. After external validation of the model in the GSE48276 dataset, we integrated the 7-ZNF-gene signature with patient clinicopathological data to construct a nomogram that forecasted 1-, 2-, and 3-year OS with good predictive accuracy. We then accessed The Genomics of Drug Sensitivity in Cancer database to predict the therapeutic drug responses of signature-defined high- and low-risk BC patients in the TCGA cohort. Greater sensitivity to chemotherapy was revealed in the low-risk group. Finally, we conducted gene set enrichment analysis of the signature genes and established, by applying the ESTIMATE algorithm, distinct correlations between the two risk groups and the presence of stromal and immune cell types in the tumor microenvironment. By allowing effective risk stratification of BC patients, our novel ZNF gene signature may enable tailoring more intensive treatment for high-risk patients.

IFI16 Can Be Used as a Biomarker for Diagnosis of Renal Cell Carcinoma and Prediction of Patient Survival.

The incidences of renal cell carcinoma (RCC) increase in number each year and account for about 2-3% of all malignant tumors. Many patients have metastasis by the time of diagnosis, and their prognosis is poor. Therefore, it is essential that new diagnostic and prognostic markers for kidney cancer are identified. In this study, we assessed the potential of IFI16 as a diagnostic and prognostic marker for RCC. We analyzed the TCGA and UALCAN databases and found IFI16 to be highly expressed in ccRCC. In addition, high IFI16 levels positively correlated with lymphatic metastasis, tumor stage, and histopathological grade. Kaplan-Meier curve analysis showed that IFI16 expression was related to the prognosis of patients, and high IFI16 expression indicated a worse overall survival (p = 5.1E-0.7). Receiver operating characteristic curve analysis showed that a combination of IFI16 expression and histopathological grade improved predictive accuracy (AUC = 0.697; 95%CI: 0.628-0.765, P < 0.001). Finally, the relative levels of IFI16 in ACHN and Caki-1 cells were higher than that of HK-2 cells by western blotting analysis and RT-PCR. Functional tests showed that knocking down IFI16 expression inhibited migration and invasion in vitro. Therefore, IFI16 is a potential biomarker for the diagnosis and prognosis of RCC patients.

The characteristics of regulatory macrophages and their roles in transplantation.

Regulatory macrophages (Mregs) are a subtype of macrophages that are involved in regulating immune responses and inhibiting activated T lymphocyte proliferation. With advances in our basic understanding of Mregs and the revelation of their biological characteristics, Mregs have become a focus of research. In addition to promoting malignant tumor progression, Mregs also play an immunosuppressive role in inflammatory diseases and transplantation. Recent studies have shown that Mregs are closely associated with the induction of transplantation immune tolerance. Immune regulatory cell treatment as an adjunct immunosuppressive therapy offers new insights into the mechanism by which transplantation immune tolerance is established. The application of Mreg-based cellular immunotherapy has shown promise in clinical solid organ transplantation. Here, we provide a comprehensive overview of Mreg morphology, phenotype, induction and negative immunoregulatory function and discuss the role of Mregs in different transplantation models as well as their potential application value in clinical organ transplantation.

Interferon-inducible protein 16 may be a biomarker and prognostic factor in renal cell carcinoma by bioinformatics analysis.

BACKGROUND: Renal cell carcinoma (RCC) accounts for 2% to 3% of all human malignancies and is the 9th most common malignancy in Western countries. Due to the development of surgical procedures and the use of novel drugs, survival has been significantly prolonged. However, current challenges include how to diagnose RCC earlier and how to overcome drug resistance. Methods: We explored the relationship between the transcription level of IFI16 and clinical data in RCC through various online databases, including ONCOMINE, GEPIA, HPA, Timer and COEXPEDIA. RESULTS: In comparison with corresponding normal tissues, IFI16 mRNA expression levels were higher in kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) tissues. In KIRC, the higher expression of IFI16 was associated with lower overall survival (P = .037). In KIRP, the higher expression IFI16 was associated with lower disease-free survival and overall survival (P = .037 and P = .011). In contrast, the IFI16 expression was negatively correlated with tumor purity in kidney chromophobe, KIRC and KIRP (all P < .05). In KIRC and KIRP, the expression of IFI16 was positively correlated with tumor-infiltrating immune cells (TIICs) (all P < .05), except macrophages in KIRP. In KIRC, the main TIICs were B cells, CD4+T cells, neutrophils, and dendritic cells, while the main TIICs in the high amplification state were macrophage (all P < .0001). Functional enrichment analysis by gene ontology and Kyoto Encyclopedia of Genes and Genomes highlighted enrichment of neutrophil degranulation, phagocytosis and vesicle-mediated transport regulation, and pathways including tuberculosis, toxoplasmosis, phagosome, leishmaniasis, and Fc gamma R-mediated. CONCLUSIONS: IFI16 is overexpressed in RCC and may be an important oncogene in the progression of kidney. In addition, IFI16 may a marker for RCC diagnosis and prognosis, which may be related to immune infiltration.

Advances of miRNAs in kidney graft injury.

Kidney transplantation is the preferred treatment for patients with end-stage renal disease. However, various types of kidney graft injury after transplantation are still key factors that affect the survival of the kidney graft. Therefore, exploring the underlying mechanisms involved is very important. Current diagnostic measures for kidney graft injury (including needle biopsy, blood creatinine, eGFR, etc.) have many limiting factors such as invasiveness, insufficient sensitivity and specificity, so they cannot provide timely and effective information to clinicians. As for kidney grafts that have occurred injury, the traditional treatment has a little efficacy and many side effects. Therefore, there is an urgent need for developing new biomarkers and targeted treatment for kidney graft injury. Recently, studies have found that miRNAs are involved in the regulation of the progression of kidney graft injury. At the same time, it has high stability in blood, urine, and other body fluids, so it is suggested to have the potential as a biomarker and therapeutic target for kidney graft injury. Here, we reviewed the miRNAs involved in the pathophysiology of kidney graft injury such as ischemia/reperfusion injury, acute rejection, drug-induced nephrotoxicity, chronic allograft dysfunction, BK virus infection, and the latest advances of miRNAs as biomarkers and therapeutic targets of kidney graft injury, then summarized the specific data of miRNAs expression level in kidney graft injury, which aims to provide a reference for subsequent basic research and clinical transformation.

Myeloid-derived suppressor cells in transplantation tolerance induction.

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells derived from bone marrow. These cells are developed from immature myeloid cells and have strong negative immunomodulatory effects. In the context of pathology (such as tumor, autoimmune disease, trauma, and burns), MDSCs accumulate around tumor and inflammatory tissues, where their main role is to inhibit the function of effector T cells and promote the recruitment of regulatory T cells. MDSCs can be used in organ transplantation to regulate the immune responses that participate in rejection of the transplanted organ. This effect is achieved by increasing the production of MDSCs in vivo or transfusion of MDSCs induced in vitro to establish immune tolerance and prolong the survival of the graft. In this review, we discuss the efficacy of MDSCs in a variety of transplantation studies as well as the induction of immune tolerance to prevent transplant rejection through the use of common clinical immunosuppressants combined with MDSCs.