UBE2A as a prognostic indicator across human cancers: Insights from multi-omics and immune landscape analyses

UBTD1 Drives Ovarian Cancer Progression via Mutation‐Associated Alterations, Stromal Microenvironment Remodeling, and TNF/AP‐1 Signaling

Background The ubiquitin domain‐containing protein 1 (UBTD1) is involved in protein homeostasis and cell cycle regulation, and emerging evidence suggests its role in tumor biology. However, its function in ovarian cancer (OC) remains unclear. OC is highly lethal due to late diagnosis, metastasis, and platinum resistance. This study is aimed at investigating the role of UBTD1 in OC by integrating single‐cell transcriptomics, mutation and HRD‐related analyses, tumor microenvironment evaluation, and experimental validation. Methods We examined UBTD1 expression, prognosis, somatic mutation features, and immune microenvironment characteristics utilizing public databases, such as the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Single‐cell RNA‐seq data were analyzed using Seurat, hdWGCNA, and CopyKAT to characterize UBTD1‐associated malignant‐cell states and inferred CNV burden. Based on the median UBTD1 expression, TCGA‐OV samples were divided into high and low expression groups to compare mutation spectra, DNA repair pathway activity, stromal scores, and immune cell infiltration. Functional assays were performed in A2780 and SK‐OV‐3 cell lines following lentiviral shRNAs‐mediated UBTD1 knockdown. RNA sequencing and rescue experiments were used to explore downstream pathways. Results Integrated single‐cell and TCGA‐OV analyses revealed that UBTD1‐low tumors were enriched for genomic instability–related features, including increased inferred CNV burden and higher tumor mutation burden. By comparison, UBTD1‐high tumors showed increased stromal scores and modest enrichment of selected immune‐cell populations, including macrophages and neutrophils. Experimentally, UBTD1 was upregulated in OC and associated with poor prognosis. UBTD1 knockdown inhibited malignant phenotypes, enhanced cisplatin sensitivity, promoted apoptosis, and suppressed TNF/AP‐1/FOS–related signaling. FOS overexpression partially reversed the effects of UBTD1 silencing. Conclusions UBTD1 expression defines distinct mutation and microenvironmental states in OC and functionally promotes malignant phenotypes, potentially through TNF/AP‐1/FOS–related signaling.

The role of KIAA1467 in breast cancer: insights from pan-cancer and single-cell sequencing analysis

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.

Integrated multi-omics analysis and functional experiments reveals PPAP2C as a potential prognostic biomarker and therapeutic target in breast cancer

Background This study aims to systematically elucidate the clinical significance and biological function of the phospholipid phosphatase (PLPP) family member (PPAP2C) phosphatidic acid phosphatase type 2C in breast cancer, and to evaluate its potential as a prognostic biomarker and therapeutic target. Methods Gene expression data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases were integrated to characterize the expression profile of PLPP family members, focusing on PPAP2C in breast cancer. The prognostic value of PPAP2C, initially identified at the mRNA level (TCGA, (METABRIC) Molecular Taxonomy of Breast Cancer International Consortium, Gene Expression Omnibus (GEO)), was confirmed at the protein level by immunohistochemistry (IHC) on tissue microarrays (TMA). The oncogenic functions of PPAP2C were investigated in triple-negative breast cancer (TNBC) cells through CRISPR-Cas9-mediated knockout and ectopic overexpression, with assessment of key phenotypes including proliferation, colony formation, migration, and invasion. In vivo validation was subsequently performed using an MDA-MB-231 xenograft model. Results PPAP2C exhibits the most significant overexpression pattern across 33 cancer types (upregulated in 16 cancers, downregulated in only 3). Compared with normal tissues, PPAP2C showed specific overexpression in breast cancer tissues and was significantly associated with advanced clinical stages and aggressive subtypes (HER2+ and TNBC). Survival analysis demonstrated that high PPAP2C expression correlated with significantly shorter overall survival and disease-free survival, which was further validated in METABRIC and GEO cohorts. Tissue microarray analysis confirmed higher PPAP2C protein positivity in tumor tissues (94.7%) than in adjacent normal tissues (59.7%), with worse OS and RFS in high-expression groups. Multivariate analysis identified PPAP2C as an independent prognostic factor for OS. Functional experiments revealed that PPAP2C knockout (via 5-bp/1-bp frameshift mutations) suppressed TNBC cell proliferation, colony formation, migration, and invasion, while overexpression enhanced these phenotypes. In vivo studies further demonstrated complete tumor regression in MDA-MB-231 xenografts upon PPAP2C knockout. Conclusion This study identifies PPAP2C as a key oncogenic driver and a robust independent prognostic biomarker in breast cancer. The findings provide compelling evidence that PPAP2C represents a promising therapeutic target, offering a new strategic avenue for precision therapy, particularly for aggressive breast cancer subtypes.

Comprehensive Analysis of m6A Regulators Identifies YTHDF3 as a Promising Prognostic Biomarker for Breast Cancer.

Collectively, m6A-related genes are dysregulated in breast cancer and correlate with patient outcomes, highlighting their biomarker potential, with YTHDF3 warranting in-depth investigation.

A pan-cancer analysis reveals the multifaceted role of PABPC1L in immune regulation and therapy response

Bioinformatic characterization of SLC25A39 across cancers with validation in hepatocellular carcinoma

Functional enrichment analysis reveals that SLC25A39 is commonly associated with immune-related pathways and cell cycle-related pathways in the pan-cancer dataset.