TL;DR
An integrated pan-cancer analysis of PABPC1L expression and function in 33 human malignant tumors identified PABPC1L as exhibiting oncogenic properties and is proposed to function as a key regulator of tumorigenesis and immunotherapy resistance.
OBJECTIVE This study aimed to clarify the pan-cancer expression pattern, upstream regulatory mechanisms, prognostic relevance, and immune associations of CDC20B. METHOD Using public databases (GTEx, GEO, and TCGA), we examined CDC20B expression and its associations with prognosis and tumor immunity across multiple cancers. Immunohistochemistry (IHC) on an independent clinical cohort was performed to validate CDC20B upregulation in tumor tissues. Promoter methylation, genetic alterations, and immune infiltration were analyzed using bioinformatics tools (cBioPortal, UALCAN, TIMER2.0, ESTIMATE). Functional enrichment was assessed by GSEA and single-cell state analysis (CancerSEA). RESULTS CDC20B was markedly upregulated in most tumor types (p < 0.001), with strong diagnostic efficiency (AUC > 0.7 in 15 cancers) and potential regulation by promoter hypomethylation. IHC confirmed its overexpression in clinical tumor tissues. However, the prognostic impact of CDC20B was cancer-type-specific: high expression correlated with poor overall survival in UCS, LGG, KIRC, and OV, but with favorable survival in BRCA, LUAD, and PAAD. CDC20B expression was associated with immune infiltration patterns, showing negative correlations with ImmuneScore in most cancers but positive correlations with CD8+ T cells in PAAD. Functional analyses indicated involvement in EMT, KRAS/NF-κB signaling, and DNA damage response pathways. DISCUSSION The dual prognostic role of CDC20B suggests context-dependent functions, likely influenced by tumor microenvironment composition and underlying oncogenic programs. Promoter hypomethylation emerges as a potential epigenetic driver of overexpression. The associations with immune modulation and genomic instability suggest that CDC20B is a candidate biomarker, though causal relationships require experimental validation. CONCLUSION CDC20B may contribute to tumor progression in a context-dependent manner, with its prognostic impact varying across cancer types. Its role in tumor immunity and oncogenic pathways warrants further investigation, particularly in stratified patient populations.
Background Improving the response rate of single-agent immune checkpoint blockade (ICB) urgently requires the discovery of new therapeutic targets for combinatorial regimens. Analyses of tumor microenvironment (TME)-associated biomarkers have verified that KIAA1467 drives the formation of an immune-excluded, non-inflamed TME in breast cancer (BRCA). This study systematically explores the expression pattern, prognostic value, immune regulatory function, biological effects, and drug resistance relevance of FAM234B (also known as KIAA1467) in BRCA. Methods We performed pan-cancer survival analysis using The Cancer Genome Atlas (TCGA) datasets. Multi-omics bioinformatics analyses were conducted to evaluate KIAA1467 expression across malignancies. Single-cell RNA sequencing (scRNA-seq) data from GSE176078 was utilized to localize KIAA1467 expression at the cellular level. Immunohistochemistry and western blot assays validated KIAA1467 expression in BRCA clinical specimens. Correlation analyses were implemented to assess relationships between KIAA1467 expression, clinicopathological features, immune modulators, tumor-infiltrating immune cells, and p53 mutation status. Functional enrichment analysis uncovered relevant signaling pathways. Bioinformatic half maximal inhibitory concentration (IC50) prediction and in vitro cellular experiments were applied to evaluate associations between KIAA1467 and chemotherapeutic drug sensitivity. Results TCGA pan-cancer survival analysis demonstrated that elevated KIAA1467 expression significantly predicted shortened overall survival in BRCA and multiple other tumor types. KIAA1467 displayed distinct expression patterns across cancers, with prominent upregulation in BRCA. scRNA-seq confirmed enriched KIAA1467 expression within BRCA cells, and its upregulation in BRCA tissues was further verified by immunohistochemistry and western blot. High KIAA1467 expression was positively correlated with advanced tumor grade and lymphatic metastasis. KIAA1467 showed negative correlations with most immune modulators and core immune checkpoint molecules, as well as tumor-infiltrating immune cells in the TME, implying its potential function in tumor immune evasion. Low KIAA1467 expression was tightly linked to p53 mutations. Enrichment analysis indicated participation of KIAA1467 in epithelial-mesenchymal transition, apoptosis and cell cycle arrest. Furthermore, high KIAA1467 expression corresponded to higher estimated IC50 values of cisplatin, gefitinib, paclitaxel and gemcitabine, consistent with reduced chemosensitivity observed in vitro. Conclusions This study reveals the multifaceted oncogenic role of KIAA1467 in BRCA. KIAA1467 participates in remodeling an immunosuppressive TME, correlates with malignant progression and chemoresistance, and may serve as a promising candidate target to optimize ICB-based combination therapy for BRCA. These findings offer new perspectives for the clinical treatment and comprehensive management of BRCA.
PPAP2C exhibits the most significant overexpression pattern across 33 cancer types and was significantly associated with advanced clinical stages and aggressive subtypes (HER2+ and TNBC).
BCAT1 expression was significantly upregulated in most malignancies, and high expression was associated with worse OS and DFS in multiple cancer types, highlighting its potential as a pan-cancer biomarker and therapeutic target.
Gastric cancer is a major malignancy with molecular heterogeneity and limited biomarkers for risk stratification and therapeutic guidance. Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2), a regulator of ribosome biogenesis, has been implicated in tumor progression, but its relevance in gastric cancer is poorly defined. This study aimed to characterize the potential pro-oncogenic and immune relevance of ISG20L2 in gastric cancer. Public multi-omics datasets and two single-cell RNA-sequencing cohorts were used to evaluate ISG20L2 expression and its associations with molecular features, tumor functional states, immune infiltration, and immunotherapy-related characteristics. Protein expression was validated in gastric cancer cell lines and nine paired clinical tissues, and functional effects of ISG20L2 knockdown were assessed in AGS and HGC-27 cells. ISG20L2 was significantly upregulated in gastric cancer and inversely correlated with promoter methylation. Single-cell analysis showed predominant enrichment of ISG20L2 in exhausted CD8+ T cells. High ISG20L2 expression was closely associated with cell-cycle activity, immune infiltration, PD-L1 expression and predicted immunotherapy response. Experimentally, ISG20L2 protein was elevated in gastric cancer cell lines and tumor tissues. ISG20L2 knockdown markedly suppressed proliferation, clonogenicity, migration and invasion in both AGS and HGC-27 cells. ISG20L2 is aberrantly upregulated and associated with malignant biological features and immune-related characteristics in gastric cancer, supporting its potential role as a pro-oncogenic regulator and a candidate molecular indicator requiring further clinical validation.
A systematic pan-cancer characterization of MEX3A is provided and supports its potential role as a prognostic biomarker and a hypothesis-generating candidate for future mechanistic and clinical validation, as well as suggesting that MEX3A may participate in RNA regulatory networks and tumor-immune microenvironment interactions.
We use cookies to run the site and, with your consent, for analytics and to show ads. See our Cookie Policy.
