Changyi Quan

Metastasis is the leading cause of death in clear cell renal cell carcinoma (ccRCC) patients. Anoikis, a form of programmed cell death induced by the loss

Background: While immune cells are pivotal in clear cell renal cell carcinoma (ccRCC), functional alterations of specific subsets and their prognostic implications remain unclear. We aimed to identify key immune cells, characterize their functional states, and develop a prognostic model by integrating single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) data. Methods: scRNA-seq dataset GSE210038 was analyzed to annotate tumor-infiltrating immune cells. Key immune cells were identified from deconvolved The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) and Gene Expression Omnibus Series (GSE)105261 datasets using support vector machine-recursive feature elimination (SVM-RFE), least absolute shrinkage and selection operator (LASSO), and random forest (RF) algorithms. Immune Response Enrichment Analysis (IREA) delineated polarization states of key immune cells in response to cytokines. Cellular communication was profiled via CellChat. Prognostic genes associated with key immune cells were screened by univariate Cox and LASSO regression. A risk score (RS) model was constructed and validated in TCGA-KIRC (training, n=511) and E-MTAB-1980 (validation, n=101) cohorts. Receiver operating characteristic (ROC) curves evaluated overall survival (OS) prediction efficacy. Nomograms and drug sensitivity analyses were performed. Results: Seven immune cell types infiltrated ccRCC. CD8⁺ T and natural killer (NK) cells were identified as the key immune cells. IREA revealed T8-c polarization in CD8⁺ T cells [enriched for interferon (IFN)-α1/interleukin (IL)-36α] and NK-f polarization in NK cells (enriched for IL-18/IL-2). CellChat analysis showed amplified protease activated receptors (PARs) signaling from key immune cells to cancer-associated fibroblasts, but attenuated Annexin A1 (ANXA1)-formyl peptide receptor 1 (FPR1) signaling to macrophages. Ten immune-cell-associated prognostic genes (PTTG1, CLEC2D, PLIN2, LRBA, ABCB1, MIR155HG, ADAM8, P2RY8, SORL1, CD82) were used to build the RS model. The model stratified patients into high/low-risk groups with distinct OS (log-rank PConclusions: CD8+ T and NK cells exhibit functional polarization and altered cellular communication indicative of augmented anti-tumor immunity in ccRCC. The immune-cell-derived 10-gene signature provides a reliable prognostic tool and guides personalized therapy.

Background Ferroptosis, a recently recognized form of regulated cell death, plays a prominent role in anti-tumor immunity. However, the potential functions of ferroptosis-related regulators in the prognosis, immune checkpoint genes expression, and immunotherapy efficacy of bladder cancer (BC) have not been systematically studied. Materials and methods We systematically evaluated the correlations between ferroptosis levels and prognosis, clinical characteristics, tumor mutation burden (TMB), immune checkpoint gene expression, and immune cell infiltration characteristics. The ferroptosis level of each patient was calculated using principal component analysis based on the expression of prognostic differentially expressed genes. Hub ferroptosis-related genes involved in immunoregulation and immunotherapy efficacy in BC were subsequently identified. Results Eighteen ferroptosis regulators were associated with the prognosis of BC. We identified three ferroptosis subgroups, which have different immune cell infiltration characteristics and distinct carcinogenesis-related immune pathways, such as immune cell differentiation, and the PD-L1/PD-1 pathway. High ferroptosis levels and ferroptosis-related gene kinesin family member 14 (KIF14) are closely associated with poor prognosis, tumor mutation burden, immune checkpoint genes expression, and immune cell infiltration. An immunotherapy cohort confirmed that patients with high KIF14 expression demonstrated significant therapeutic and clinical benefits. Conclusions The study revealed that ferroptosis level and KIF14 were significantly related to prognosis, immune checkpoint genes expression, immune cell infiltration, and immunotherapy response in BC.

Background: Hypertension is a major public health problem. In clinical practice, we have observed that when hypertensive patients undergo robotic-assisted partial nephrectomy (RAPN), approximately half of them experience a normalization of their blood pressure (BP) shortly after the surgery. This study aims to investigate the effect of RAPN on BP in hypertensive patients with renal tumor by disassociating nerve tissue around the renal artery.

Recent studies have identified a biological process called adherent-to-suspension transition (AST) as a key factor in promoting metastasis. The involvement of AST in the progression of clear cell renal cell carcinoma (ccRCC) remains largely unexplored. We comprehensively investigated the overall landscape of all 20 AST factors at the pan-cancer level. The risk stratification method and the prognostic model based on AST factors were established with consensus clustering analysis and LASSO regression algorithm. The potential molecular mechanism of AST was further investigated by multi-omics analysis and cell experiments. We found that AST factors play distinct roles in different cancer types. Consequently, we utilized AST factors to develop a risk stratification method and a prognostic model, which can effectively guide the treatment of ccRCC patients. We proposed that the promotion of AST is facilitated by SPIB through the SAA1-AKT pathway, enhancing the likelihood of ccRCC metastasis, and conducted rigorous analyses using multi-omics data and cellular experiments. Our study presents a novel risk stratification method and prognostic model for ccRCC. And we identified the SPIB-SAA1-AKT pathway as one of the potential mechanisms by which AST factors promote ccRCC metastasis.

Matrix Metalloproteinases (MMPs) have been demonstrated to be essential in facilitating the migration and metastasis of clear cell renal cell carcinoma (ccRCC). However, the ability of the MMP family to predict clinical outcomes and guide optimal therapeutic strategies for ccRCC patients remains incompletely understood. In this investigation, we initially conducted a thorough examination of the MMP family in pan-cancer. Notably, MMPs exhibited distinctive significance in ccRCC. Following this, we undertook an extensive analysis to evaluate the clinical value of MMPs and potential mechanisms by which MMPs contribute to the progression of ccRCC. A novel stratification method and prognostic model were developed based on MMPs in order to enhance the accuracy of prognosis prediction for ccRCC patients and facilitate personalized treatment. By conducting multi-omics analysis and transcriptional regulation analysis, it was hypothesized that SAA1 plays a crucial role in promoting ccRCC migration through MMPs. Subsequently, in vitro experiments confirmed that SAA1 regulates ccRCC cell migration via the ERK-AP1-MMPs axis. In conclusion, our study has explored the potential value of the MMP family as prognostic markers for ccRCC and as guides for medication regimens. Additionally, we have identified SAA1 as a crucial factor in the migration of ccRCC.

Background: Periodontitis and benign prostatic hyperplasia (BPH) are all common chronic diseases with higher incidence in middle-aged and old men. Several studies have indicated a potential association between periodontitis and BPH, although the findings remain inconclusive. However, there is no mendelian randomization (MR) studies to assess this association.Methods: The 40 men who had received health check-ups were included in an epidemiological study. Genetic data of BPH (13118 cases and 72799 controls) and periodontitis (3046 cases and 195395 controls) from FinnGen project was used to perform two-sample MR analysis. The inverse-variance weighted (IVW) model was identified as the primary analytical method, with MR Egger, weighted median, simple mode, and weighted mode serving as additional approaches.Results: The epidemiological analysis demonstrated a lack of statistically significant differences in the prevalence of clinical BPH between severe periodontitis group and non-severe periodontitis group. Similarly, no statistically significant differences were found in the prevalence of severe periodontitis among individuals with clinical BPH compared to those without. Additionally, Among the five models utilized in MR analysis, including the IVW model, no evidence of a causal link between periodontitis and BPH was observed.Conclusion: The findings from our epidemiological investigation and MR analysis do not provide support for a causal relationship between periodontitis and BPH.