In this study, we aimed to perform a pan-cancer analysis of leucine zipper protein 2 (LUZP2). A standardized TCGA pan-cancer dataset was downloaded. Differential expression, clinical prognosis, genetic mutations, immune infiltration, epigenetic modifications, tumor stemness and heterogeneity were analyzed. We conducted all analyses through software R 3.6.3 and its suitable packages. Compared to normal samples, we observed that the LUZP2 mRNA expression was significantly upregulated in LGG, PRAD, LUSC and downregulated in KIRC and other eleven cancer species patients. In terms of overall survival, low-expression of LUZP2 was significantly associated with poor prognosis in lower grade glioma (LGG), lung squamous cell carcinoma (LUSC), kidney renal clear cell carcinoma (KIRC) and prostate adenocarcinoma (PRAD). For progression-free survival, we observed that downregulation of LUZP2 was significantly related to LGG, KIRC, LUSC, and PRAD. Our results observed negative correlations of the stemness of LGG and PRAD with the mRNA expression of LUZP2, whose downregulation was closely associated with poor prognosis. The mutation frequencies of LGG, PRAD, KIRC, and LUSC were 0.4%, 0.4%, 0.3%, and 2.1%, respectively. We detected that the LUZP2 level was negatively associated with TILs in most cancers, including LGG, LUSC, PRAD, and KIRC, while the LUZP2 methylation showed the opposite results. In conclusion, the results of our initial pan-cancer investigation provided a somewhat thorough understanding of the functions of LUZP2 on KIRC, LGG, PRAD, and LUSC.

We identified distinct senescence-related molecular subtypes and critical genes among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). We conducted all analyses using R software and its suitable packages. Twelve genes, namely, secreted frizzled-related protein 4 ( SFRP4 ), DNA topoisomerase II alpha ( TOP2A ), pleiotrophin ( PTN ), family with sequence similarity 107 member A ( FAM107A ), C-X-C motif chemokine ligand 14 ( CXCL14 ), prostate androgen-regulated mucin-like protein 1 ( PARM1 ), leucine zipper protein 2 ( LUZP2 ), cluster of differentiation 38 ( CD38 ), cartilage oligomeric matrix protein ( COMP ), vestigial-like family member 3 ( VGLL3 ), apolipoprotein E ( APOE ), and aldehyde dehydrogenase 2 family member ( ALDH2 ), were eventually used to subtype PCa patients from The Cancer Genome Atlas (TCGA) database and GSE116918, and the molecular subtypes showed good correlations with clinical features. In terms of the tumor immune environment (TME) analysis, compared with cluster 1, cancer-associated fibroblasts (CAFs) scored significantly higher, while endothelial cells scored lower in cluster 2 in TCGA database. There was a statistically significant correlation between both CAFs and endothelial cells with biochemical recurrence (BCR)-free survival for PCa patients undergoing RP. For the GSE116918 database, cluster 2 had significantly lower levels of CAFs and tumor purity and higher levels of stromal, immune, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) scores than cluster 1; in addition, patients with high levels of CAFs, stromal scores, immune scores, and ESTIMATE scores and low levels of tumor purity tended to suffer from BCR. Based on the median of differentially expressed checkpoints, high expression of CD96 , hepatitis A virus cellular receptor 2 ( HAVCR2 ), and neuropilin 1 ( NRP1 ) in GSE116918 and high expression of CD160 and tumor necrosis factor (ligand) superfamily member 18 ( TNFSF18 ) in TCGA database were associated with a significantly higher risk of BCR than their counterparts. In conclusion, we first constructed distinct molecular subtypes and critical genes for PCa patients undergoing RP or RT from the fresh perspective of senescence.

Background N7-methylguanosine (m7G) is closely associated with tumor prognosis and immune response in many cancer types. The correlation between m7G and bladder cancer (BC) needs further study. We aimed to orchestrate molecular subtypes and identify key genes for BC from the perspective of m7G. Methods RNA-seq and clinical data of BC patients were extracted from TCGA and GSE13507 datasets. The patients were subtyped by “ConsensusClusterPlus” and “limma.” The clusters were validated by the Kaplan‒Meier curves, univariable and multivariate Cox regression models, the concordance index, and calibration curves. The immunotherapy response was evaluated by immune checkpoints, immune infiltration, TIDE score, and IMvigor210 cohort. Genomics of Drug Sensitivity in Cancer was utilized to predict the chemotherapy response between the clusters. Results The m7G-related cluster was ultimately established by EIF4G1, NUDT11, NUDT10, and CCNB1. The independent prognostic value of the m7G-related cluster was validated by the TCGA and GSE13507 datasets. The cluster was involved in immune-associated pathways, such as neutrophil degranulation, antigen processing cross-presentation, and signaling by interleukins pathways. Meanwhile, cluster 2 was positively correlated with many immune checkpoints, such as CD274, CTLA4, HAVCR2, LAG3, PDCD1, and PDCD1LG2. The cluster 2 was significantly correlated with a higher TIDE score than the cluster 1. Furthermore, in the IMvigor210 cohort, patients in the cluster 1 had a higher response rate than those in the cluster 2. Patients in the cluster 2 were sensitive to many chemotherapies. Conclusions We successfully determined molecular subtypes and identified key genes for BC from the perspective of m7G, thereby providing a roadmap for the evolution of immunotherapy and precision medicine.

BackgroundAs a ferroptosis-related gene, the polymorphism of zinc finger protein 419 (ZNF419) at the splice donor site may generate renal cell carcinoma-associated novel minor histocompatibility antigen ZAPHIR. However, the role of ZNF419 in prognosis and immunology in human tumors remains largely unknown. This study aimed to visualize the prognostic landscape of ZNF419 at pan-cancer level and explore the relationship between ZNF419 expression and the tumor immune microenvironment.MethodPan-cancer and mutation data were downloaded from TCGA databases and analyzed through R (version 3.6.4) and its suitable packages. Differential ZNF419 expression and prognosis were analyzed. Correlations with ferroptosis-related genes, pathway analysis, tumor stemness, heterogeneity, mutation landscape, and RNA modifications were also explored. The relationships between ZNF419 expression and tumor immunity were investigated through the TIMER and ESTIMATE methods.ResultZNF419 was differentially expressed between tumor and normal samples and was associated with overall survival, disease-specific survival and progression-free interval for STES, KIRC, LIHC, LUSC, PRAD, and BLCA. We found the interaction between ZNF419 and FANCD2 might involve in ferroptosis in pan-cancer level. In addition, the mutation frequencies of STES, KIRC, LIHC, LUSC, PRAD, and BLCA were 1.5%, 0.3%, 0.3%, 1.9%, 0.2%, and 0.7%, respectively. We detected that the expression of ZNF419 was closely correlated with most immune checkpoint genes and immune regulatory genes. Furthermore, we found that the ZNF419 expression level was negatively related to the immune score in the six cancers mentioned above. The expression of ZNF419 was significantly associated with various infiltrating immune cells, such as CD4+ T cells, CD8+ T cells, and macrophages in patients with KIRC, PRAD, and LUSC but was only significantly related to macrophages in BLCA patients.ConclusionZNF419 might serve as a potential prognostic and immunological pan-cancer biomarker, especially for KIRC, LIHC, LUSC, PRAD, and BLCA.

Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore that is required for proper chromosomal segregation and cell division. However, little is known regarding the probable mechanism of SKA3, particularly in terms of prostate cancer (PCA) progression. Multiple databases, including TCGA and GTEx, were utilized to examine the expression of SKA3 in PCA patients and to shed light on the clinical significance and potential mechanism of SKA3 in the onset and progression of PCA. The biological function of SKA3 was evaluated in vitro using RT–qPCR and the CCK8 assay. For statistical analysis, the R 3.6.3 software and its associated packages were utilized. SKA3 was shown to be considerably elevated in PCA patients and was linked to a shorter progress free interval (PFI). Furthermore, we discovered that SKA3 mRNA expression was higher in PCA cells than in normal cells, and inhibition of SKA3 could clearly reduce PCA cell proliferation using the CCK8 assay. Finally, SKA3 could be used as a predictive biomarker in PCA patients.