TNFAIP8 family molecules have been recognized for their involvement in the progression of tumors across a range of cancer types. Emerging experimental data suggests a role for certain TNFAIP8 family molecules in the development of glioma. Nonetheless, the comprehensive understanding of the genomic alterations, prognostic significance, and immunological profiles of TNFAIP8 family molecules in glioma remains incomplete. In the study, using the comprehensive bioinformatics tools, we explored the unique functions of 4 TNFAIP8 members including TNFAIP8, TNFAIP8L1, TNFAIP8L2 and TNFAIP8L3 in glioma. The expressions of TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 were notably upregulated in glioma tissues compared to normal tissues. Furthermore, survival analysis indicated that elevated expression levels of TNFAIP8, TNFAIP8L1 and TNFAIP8L2 were correlated with unfavorable outcomes in terms of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) among glioma patients. Genetic modifications, such as mutations and copy number alterations, within the TNFAIP8 family exhibited a significant association with extended OS, DSS and PFS in individuals diagnosed with glioma. The findings suggest a noteworthy correlation between TNFAIP8 family members and the age and 1p/19q codeletion status of glioma patients. We also found that there were significant relationships between TNFAIP8 family expression and tumor immunity in glioma. Furthermore, functional annotation of TNFAIP8 family members and their co-expressed genes in gliomas was carried out using GO and KEGG pathway analysis. The GO analysis revealed that the primary biological processes influenced by the TNFAIP8 family co-expressed genes included cell chemotaxis, temperature homeostasis, and endocytic vesicle formation. Additionally, the KEGG analysis demonstrated that TNFAIP8 family co-expressed genes are involved in regulating various pathways such as inflammatory mediator regulation of TRP channels, pathways in cancer, prolactin signaling pathway, and Fc gamma R-mediated phagocytosis. Overall, the findings suggest that TNFAIP8 family members may play a significant role in the development of glioma and have the potential to serve as prognostic indicators and therapeutic targets for individuals with glioma.

Purpose RING Finger 187 (RNF187) has recently emerged as a potential contributor to tumorigenesis. However, a comprehensive pan-cancer analysis of RNF187 in human tumors has not been undertaken until now. Methods Our study aims to investigate RNF187 expression across 33 different types of human tumors, utilizing data from the TCGA and GTEx databases. Results The pan-cancer analysis revealed significant upregulation of RNF187 in 27 types of cancers, contrasting with only low expression in LAML, with no statistical differences in OV and SARC. Notably, discernible associations were identified between RNF187 expression and the prognosis of cancer patients. Our investigation also unveiled correlations between RNA modification of RNF187 across various cancer types. Further exploration indicated a positive correlation between RNF187 levels and the presence of cancer-associated fibroblasts (CAFs) in numerous tumor types. Additionally, RNF187 exhibited correlations with a majority of immune inhibitory and stimulatory genes, as well as chemokines, receptors, MHC molecules, immunoinhibitors, and immunostimulators in various cancers. The findings highlighted associations between RNF187 expression and Tumor Mutational Burden (TMB), Microsatellite Instability (MSI) and Homologous Recombination Deficiency (HRD) in specific tumors. Finally, RNF187 showed a significant positive association with five genes (ALKBH4, FAM134A, MLST8, SANP47 and TMEM9) across the majority of tumors. GO enrichment and KEGG pathway analyses suggested that RNF187 may play a role in the pathogenesis of cancer through processes such as "bounding membrane of organelle," "macroautophagy," "proton-transporting V-type ATPase complex," "autophagy," "Ubiquitin mediated proteolysis," "Ferroptosis," "Phagosome," and etc. Conclusion Our inaugural pan-cancer study aims to provide a profound understanding of RNF187 in tumorigenesis across diverse types of tumors.

Background ENOPH1 (Enolase-phosphatase 1), a member of the HAD-like hydrolase superfamily, has been linked to a range of physiological conditions, including neurological disorders. However, its involvement in tumorigenesis remains underexplored. This study is the first to conduct a pan-cancer analysis of ENOPH1, aiming to elucidate its role in multiple cancers through various bioinformatics platforms. Methods We conducted a thorough analysis using data from UCSC databases. ENOPH1 expression in tumor and normal tissues was evaluated using R language software. Survival analyses, genetic alterations, and RNA modifications were assessed through the GEPIA2 and cBioPortal platforms. The relationships between ENOPH1 and immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and homologous recombination deficiency (HRD) were examined using TIMER2 and R software. ENOPH1-related gene enrichment analysis was performed using the STRING and GEPIA2 databases, followed by Gene Ontology (GO) and KEGG pathway enrichment analyses. Results ENOPH1 expression was significantly upregulated in various cancers, including ACC, BLCA, BRCA, and COAD. High ENOPH1 expression was associated with poor overall survival (OS) in cancers such as KICH, LIHC, BRCA and LUAD. High ENOPH1 expression was associated with poor disease specific survival (DSS) in cancers such as KICH, LIHC, BRCA and MESO. Genetic alterations of ENOPH1, primarily mutations and deep deletions, were identified in UCEC, BLCA, and OV. ENOPH1 showed significant correlations with RNA modifications (m1A, m5C, m6A), immune checkpoints, and immune modulators across multiple cancer types. ENOPH1 was positively correlated with TMB, MSI, and HRD in cancers like BLCA, BRCA, and STAD. Furthermore, enrichment analysis revealed that ENOPH1 interacts with proteins involved in critical pathways such as AMPK, Hippo, and PI3K-AKT, suggesting its role in cancer progression. Conclusion This pan-cancer analysis reveals ENOPH1’s potential as a prognostic biomarker and its involvement in key signaling pathways across multiple cancers. Our findings provide new insights into the role of ENOPH1 in tumorigenesis and highlight its potential as a therapeutic target in cancer treatment.

Introduction The TOR signaling pathway regulator-like (TIPRL) gene plays a multifaceted role in cancer, yet its pan-cancer profile remains underexplored. This study investigates TIPRL expression across multiple cancers and its associations with survival, genetic alterations, immune infiltration, and functional pathways, providing insights into TIPRL’s role as a potential prognostic and therapeutic target. Methods TIPRL expression and prognostic significance across tumor types were analyzed using TCGA_GTEx and CPTAC data in R software and platforms like GEPIA2 and UALCAN. Genetic alterations and 3D structures were evaluated through cBioPortal. Associations with RNA modifications, immune checkpoints, immune cell infiltration, TMB, MSI, HRD, and enriched pathways were assessed via R and STRING databases, employing survival analysis, ssGSEA, and enrichment analyses. Results TIPRL expression was elevated in most cancers, with significant stage-specific associations observed in KICH, KIRP, and LUSC. High TIPRL expression correlated with worse overall survival in ACC, BRCA, HNSC, KICH, LIHC, and MESO, suggesting its role in prognosis. Genetic analysis identified amplifications as the main alteration, with varied clinical relevance across cancers. RNA modifications in TIPRL, particularly m1A, m5C, and m6A, suggested potential regulatory mechanisms. Immune infiltration analysis revealed TIPRL’s varied correlations with immune cell types and immune scores, differing by cancer type. TIPRL also positively correlated with TMB, MSI, and HRD in several cancers, indicating its association with genomic instability. Enrichment analyses highlighted TIPRL's involvement in processes like oxidative phosphorylation and autophagy, underscoring its influence in tumorigenesis. Conclusion These findings establish TIPRL as a significant biomarker in cancer progression and immune regulation, warranting further exploration into its therapeutic implications across diverse tumor types.

Background Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy with poor prognosis and high relapse rates. While the TNFAIP8 gene family (TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3) is implicated in cancer and immune regulation, its role in AML remains unclear. This study utilized bioinformatics analyses to investigate their expression, prognostic significance, genetic alterations, and immune associations in AML. Methods The expression levels and clinical significance of TNFAIP8 family genes in AML were evaluated using UCSC XENA databases. Kaplan–Meier survival analysis was performed to assess overall survival (OS) differences, and receiver operating characteristic (ROC) curves were utilized to evaluate the prognostic predictive abilities of these genes. Genetic alterations were analyzed using the cBioPortal platform, while immune infiltration was examined through ssGSEA and Spearman correlation analysis. Functional enrichment analysis of co-expressed genes was conducted using the KEGG and GO databases. Results TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 were significantly overexpressed in AML tissues compared to normal tissues (P < 0.001). However, Kaplan–Meier survival analysis revealed no significant association between their expression levels and OS in AML patients. ROC curve analysis showed that TNFAIP8L2 had the highest predictive accuracy (AUC = 1.000) among the family members, followed by TNFAIP8L1 (AUC = 0.728), TNFAIP8 (AUC = 0.709), and TNFAIP8L3 (AUC = 0.629). Clinicopathological analysis indicated that TNFAIP8 and TNFAIP8L1 expressions were associated with poor cytogenetic risk, while TNFAIP8L3 expression correlated strongly with elevated bone marrow blasts (P < 0.001). Mutation analysis revealed a low frequency of genetic alterations, with TNFAIP8L1 being the only gene with mutations in 0.53% of cases. Immune infiltration analysis demonstrated that TNFAIP8 and TNFAIP8L3 were positively correlated with myeloid-derived suppressor cells (MDSCs), while TNFAIP8L1 expression was associated with natural killer (NK) cell enrichment. Conclusion TNFAIP8 family genes play distinct roles in AML pathogenesis and immune regulation. TNFAIP8L2 shows promise as a prognostic biomarker, while TNFAIP8 and TNFAIP8L1 may indicate adverse cytogenetic risk. The study highlights their potential as therapeutic targets in AML.

Background: Cell cycle protein-dependent kinase inhibitor protein 3 (CDKN3), as a member of the protein kinase family, has been demonstrated to exhibit oncogenic properties in several tumors. However, there are no pan-carcinogenic analyses for CDKN3. Methods: Using bioinformatics tools such as The Cancer Genome Atlas (TCGA) and the UCSC Xena database, a comprehensive pan-cancer analysis of CDKN3 was conducted. The inverstigation encompassed the examination of CDKN3 function actoss 33 different kinds of tumors, as well as the exploration of gene expressions, survival prognosis status, clinical significance, DNA methylation, immune infiltration, and associated signal pathways. Results: CDKN3 was significantly upregulated in most of tumors and correlated with overall survival (OS) of patients. Methylation levels of CDKN3 differed significantly between tumors and normal tissues. In addition, infiltration of CD4 + T cells, cancer-associated fibroblasts, macrophages, and endothelial cells were associated with CDKN3 expression in various tumors. Mechanistically, CDKN3 was associated with P53, PI3K-AKT, cell cycle checkpoints, mitotic spindle checkpoint, and chromosome maintenance. Conclusion: Our pan-cancer analysis conducted in the study provides a comprehensive understanding of the involvement of CDKN3 gene in tumorigenesis. The findings suggest that targeting CDKN3 may potentially lead to novel therapeutic strategies for the treatment of tumors.