circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4.

Background: Clear cell renal cell carcinoma (ccRCC) represents the most prevalent subtype, accounting for nearly 80% of all RCC cases. Recent research has shown that high expression of circular non-coding RNA (circRNA) is associated with poor prognosis in patients with renal clear cell carcinoma (ccRCC), however, the underlying mechanism remains unclear.

Methods: After analysing self-sequenced renal cancer and paracancer circRNA sequencing data and comparing it with the GEO public database, we discovered that circASAP1 expression was significantly up-regulated in renal cancers.

Methionine-driven YTHDF1 expression facilitates bladder cancer progression by attenuating RIG-I-modulated immune responses and enhancing the eIF5B-PD-L1 axis.

The impact of amino acids on tumor immunotherapy is gradually being uncovered. In this study, we screened various essential and non-essential amino acids and found that methionine enhances mRNA methylation and reduced the activation of Type I interferon pathway in bladder cancer. Through RNA sequencing, point mutations, MB49 mouse tumor models, and single-cell RNA sequencing, we demonstrated that high methionine levels elevate the expression of mA reader YTHDF1, promoting the degradation of RIG-I, thereby inhibiting the RIG-I/MAVS-mediated IFN-I pathway and reducing the efficacy of tumor immunotherapy.

Machine learning-derived natural killer cell signature predicts prognosis and therapeutic response in clear cell renal cell carcinoma.

Background: Natural killer cells, interconnected with patient prognosis and treatment response, play a pivotal role in the tumor immune microenvironment and may serve as potential novel predictive biomarkers for renal cell carcinoma.

Methods: Clear cell renal cell carcinoma transcriptome data and the corresponding clinical data were obtained from the Cancer Genome Atlas (TCGA) database. Single-cell sequencing data were sourced from the Gene Expression Omnibus (GEO) database.

Altered tumor microenvironment heterogeneity of penile cancer during progression from non-lymphatic to lymphatic metastasis.

Background: Lymphatic metastasis is the major challenge in the treatment of penile cancer. The prognosis of individuals with lymphatic metastasis is extremely poor. Therefore, early identification of disease progression and lymphatic metastasis is an urgent task for researchers in penile cancer worldwide.

Nuclear translocation of ISG15 regulated by PPP2R2B inhibits cisplatin resistance of bladder cancer.

Cisplatin resistance is a major challenge for systemic therapy against advanced bladder cancer (BC). Little information is available on the regulation of cisplatin resistance and the underlying mechanisms require elucidation. Here, we detected that downregulation of the tumor suppressor, PPP2R2B (a serine/threonine protein phosphatase 2 A regulatory subunit), in BC promoted cell proliferation and migration.

Exploring the oncogenic potential of circSOD2 in clear cell renal cell carcinoma: a novel positive feedback loop.

Background: Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated.

Methods: Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation.

A nomogram based on TFE3 IHC results and clinical factors as a preliminary screening scheme for TFE3-rearranged renal cell carcinoma.

Background: TFE3 immunohistochemistry (TFE3-IHC) is controversial in the diagnosis of TFE3-rearranged renal cell carcinoma (TFE3-rearranged RCC). This study is to investigate the accuracy and sensitivity of IHC and establish a predictive model to diagnose TFE3-rearranged RCC.

Methods: Retrospective analysis was performed by collecting IHC and fluorescence in situ hybridization (FISH) results from 228 patients.

LRP1 induces anti-PD-1 resistance by modulating the DLL4-NOTCH2-CCL2 axis and redirecting M2-like macrophage polarisation in bladder cancer.

The tumour microenvironment (TME) drives bladder cancer (BLCA) progression. Targeting the TME has emerged as a promising strategy for BLCA treatment in recent years. Furthermore, checkpoint blockade therapies are only beneficial for a minority of patients with BLCA, and drug resistance is a barrier to achieving significant clinical effects of anti-programmed cell death protein-1 (PD-1)/programmed death protein ligand-1 (PD-L1) therapy.

PABPC1L Induces IDO1 to Promote Tryptophan Metabolism and Immune Suppression in Renal Cell Carcinoma.

Unlabelled: The tumor microenvironment (TME) in renal cell carcinomas (RCC) is marked by substantial immunosuppression and immune resistance despite having extensive T-cell infiltration. Elucidation of the mechanisms underlying immune evasion could help identify therapeutic strategies to boost the efficacy of immune checkpoint blockade (ICB) in RCC. This study uncovered a mechanism wherein the polyadenylate-binding protein PABPC1L modulates indoleamine 2,3-dioxygenase 1 (IDO1), a prospective target for immunotherapy.

Human papillomavirus infection affects treatment outcomes and the immune microenvironment in patients with advanced penile squamous cell carcinoma receiving programmed cell death protein 1 inhibitor-based combination therapy.

Background: Penile squamous cell carcinoma (PSCC) is a human papillomavirus (HPV)-associated malignancy. Immunotherapy is emerging as a potential treatment for advanced PSCC. In this study, the authors analyzed the association of HPV status with outcomes and the immune microenvironment in patients with advanced PSCC undergoing programmed cell death protein 1 (PD1) inhibitor-based combination therapy (PCT).

A novel multimodal prediction model based on DNA methylation biomarkers and low-dose computed tomography images for identifying early-stage lung cancer.

Objective: DNA methylation alterations are early events in carcinogenesis and immune signalling in lung cancer. This study aimed to develop a model based on short stature homeobox 2 gene ()/prostaglandin E receptor 4 gene () DNA methylation in plasma, appearance subtype of pulmonary nodules (PNs) and low-dose computed tomography (LDCT) images to distinguish early-stage lung cancers.

Methods: We developed a multimodal prediction model with a training set of 257 individuals.

Bladder cancer intrinsic LRFN2 drives anticancer immunotherapy resistance by attenuating CD8 T cell infiltration and functional transition.

Background: Immune checkpoint inhibitor (ICI) therapy improves the survival of patients with advanced bladder cancer (BLCA); however, its overall effectiveness is limited, and many patients still develop immunotherapy resistance. The leucine-rich repeat and fibronectin type-III domain-containing protein (LRFN) family has previously been implicated in regulating brain dysfunction; however, the mechanisms underlying the effect of LRFN2 on the tumor microenvironment (TME) and immunotherapy remain unclear.

Methods: Here we combined bulk RNA sequencing, single-cell RNA sequencing, ProcartaPlex multiple immunoassays, functional experiments, and TissueFAXS panoramic tissue quantification assays to demonstrate that LRFN2 shapes a non-inflammatory TME in BLCA.

Mitochondria-ER contact mediated by MFN2-SERCA2 interaction supports CD8 T cell metabolic fitness and function in tumors.

Metabolic fitness of T cells is essential for their vitality, which is largely dependent on the behavior of the mitochondria. The nature of mitochondrial behavior in tumor-infiltrating T cells remains poorly understood. In this study, we show that mitofusin-2 (MFN2) expression is positively correlated with the prognosis of multiple cancers.

Development and external validation of the multichannel deep learning model based on unenhanced CT for differentiating fat-poor angiomyolipoma from renal cell carcinoma: a two-center retrospective study.

Purpose: There are undetectable levels of fat in fat-poor angiomyolipoma. Thus, it is often misdiagnosed as renal cell carcinoma. We aimed to develop and evaluate a multichannel deep learning model for differentiating fat-poor angiomyolipoma (fp-AML) from renal cell carcinoma (RCC).

Hsa_circ_0057105 modulates a balance of epithelial-mesenchymal transition and ferroptosis vulnerability in renal cell carcinoma.

Background: The incidence of renal cell carcinoma (RCC) has increased in recent years. Metastatic RCC is common and remains a major cause of mortality. A regulatory role for circular RNAs (circRNAs) in the occurrence and progression of RCC has been identified, but their function, molecular mechanisms, and potential clinical applications remain poorly understood.

PD-L1 Expression is Linked to Tumor-Infiltrating T-Cell Exhaustion and Adverse Pathological Behavior in Pheochromocytoma/Paraganglioma.

Pheochromocytoma/paraganglioma (PPGL) is an endocrine-related tumor associated with excessive catecholamine release and has limited treatment options once metastasis occurs. Although recent phase 2 clinical trials of immune checkpoint inhibitors in the treatment of PPGL have preliminarily shown promising results, the fundamentals of immunotherapy for PPGL have not yet been established. In the early research, using bulk RNA sequencing of tumor samples from 7 PPGL patients, we found that PPGL tumor tissues exhibited high PD-L1 mRNA expression compared with adjacent normal adrenal medulla tissues, and this was related to T-cell exhaustion biomarkers.

Single-cell and spatial transcriptomics reveal 5-methylcytosine RNA methylation regulators immunologically reprograms tumor microenvironment characterizations, immunotherapy response and precision treatment of clear cell renal cell carcinoma.

Clear cell Renal Cell Carcinoma (ccRCC) is a highly heterogeneous disease, making it challenging to predict prognosis and therapy efficacy. In this study, we aimed to explore the role of 5-methylcytosine (m5C) RNA modification in ccRCC and its potential as a predictor for therapy response and overall survival (OS). We established a novel 5-methylcytosine RNA modification-related gene index (M5CRMRGI) and studied its effect on the tumor microenvironment (TME) using single-cell sequencing data for in-depth analysis, and verified it using spatial sequencing data.

MFN2 suppresses clear cell renal cell carcinoma progression by modulating mitochondria-dependent dephosphorylation of EGFR.

Background: Clear cell renal cell carcinoma (ccRCC) is the most lethal renal cancer. An overwhelming increase of patients experience tumor progression and unfavorable prognosis. However, the molecular events underlying ccRCC tumorigenesis and metastasis remain unclear.

Fatty acids metabolism affects the therapeutic effect of anti-PD-1/PD-L1 in tumor immune microenvironment in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is a highly invasive and metastatic subtype of kidney malignancy and is correlated with metabolic reprogramming for adaptation to the tumor microenvironment comprising infiltrated immune cells and immunomodulatory molecules. The role of immune cells in the tumor microenvironment (TME) and their association with abnormal fatty acids metabolism in ccRCC remains poorly understood.

Method: RNA-seq and clinical data of KIRC from The Cancer Genome Atlas (TCGA) and E-MTAB-1980 from the ArrayExpress dataset.

Exosomal circSPIRE1 mediates glycosylation of E-cadherin to suppress metastasis of renal cell carcinoma.

Metastasis is the main cause of mortality in renal cell carcinoma (RCC). Circular RNAs (circRNAs) involvement in RCC metastasis has been described, although the underlying mechanisms remain unknown. We evaluated recurring lung-metastasis cases using patient-derived xenograft models and isolated a highly metastatic clone.