Aug 2026· Frontiers in Oncology· Vol 16· 0 citations· 47 references
Medicine
TL;DR
ULBP1 may serve as a potential novel prognostic biomarker in BC, and targeting ULBP1 may provide a new therapeutic strategy for BC.
Abstract
Background Breast cancer (BC) is the most common malignant tumor among women worldwide. ULBP1 (UL16 binding protein 1), as a ligand of NKG2D, has been associated with poor prognosis in multiple cancers; however, its role in BC remains unclear. Methods TCGA and GEO datasets (TCGA-BRCA, GSE36295, and GSE1379) were used to evaluate the expression characteristics of ULBP1 and its association with prognosis. Functional enrichment analyses were subsequently performed to identify key biological pathways. The CIBERSORT and oncoPredict algorithms were applied to assess immune infiltration features and differences in drug sensitivity, respectively. In addition, qRT-PCR, western blotting, as well as CCK-8 and Transwell assays were conducted to validate ULBP1 expression in BC cells and to examine its effects on cellular functions. Results Analysis of public datasets revealed that ULBP1 is significantly overexpressed in BC tissues, and its high expression was independently associated with shortened overall survival. GSEA revealed that high ULBP1 expression was significantly enriched in immune-related pathways, including natural killer cell–mediated cytotoxicity. Immune infiltration analysis indicated that high ULBP1 expression was closely associated with neutrophil enrichment and the upregulation of multiple immune checkpoint genes. Drug sensitivity prediction showed that patients with high ULBP1 expression may be more sensitive to olaparib and other agents. In vitro experiments further confirmed that ULBP1 was highly expressed in BC cell lines, and that knockdown of ULBP1 significantly suppressed MCF-7 cell viability and reduced migratory and invasive capacities. Conclusion ULBP1 may serve as a potential novel prognostic biomarker in BC, and targeting ULBP1 may provide a new therapeutic strategy for BC.
CCHC zinc finger protein 10 (ZCCHC10) has been implicated in the progression of multiple malignancies, but its prognostic value and role in immune infiltration in breast cancer remain unclear. In this study, we systematically analyzed ZCCHC10 expression using public databases and validated the findings by immunohistochemistry. Associations with clinicopathological features and patient prognosis were assessed, and a prognostic nomogram was constructed. Co-expression networks and gene set enrichment analysis were used to explore functional pathways, while immune infiltration was evaluated and potential therapeutic agents were predicted. Functional assays, including proliferation and colony formation experiments, were performed to examine the biological role of ZCCHC10 in vitro. Our results demonstrated that ZCCHC10 was significantly upregulated in breast cancer and associated with poor prognosis and adverse clinicopathological characteristics. Enrichment analysis indicated involvement in immune-related pathways, and its expression correlated with immune cell infiltration and immunomodulators. Drug sensitivity prediction suggested Ipatasertib as a candidate targeted therapy requiring experimental verification. Knockdown of ZCCHC10 markedly inhibited breast cancer cell proliferation. Collectively, these findings suggest that ZCCHC10 serves as a prognostic biomarker and a key regulator of immune infiltration in breast cancer.
Miao Chen, Si-Qi Wang, Xiang Li et al.· Scientific Reports· 0 citations
OBJECTIVE
To investigate FUBP1 expression, its prognostic value, impact on the tumor microenvironment (TME), and drug sensitivity in colorectal cancer (CRC), and to explore its potential underlying mechanisms.
METHODS
Using data from The Cancer Genome Atlas (TCGA), we analyzed FUBP1 expression in CRC, evaluated its prognostic value via survival analysis and nomogram construction, performed pathway enrichment analysis, and assessed immune cell infiltration and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) scores. We further conducted immunohistochemistry (IHC) validation on an independent institutional cohort and analyzed the Gene Expression Omnibus (GEO) single-cell RNA sequencing dataset GSE132465 (n = 63,689 cells) to examine the association between FUBP1 expression and the tumor immune microenvironment at single-cell resolution.
RESULTS
FUBP1 was highly expressed in CRC (P < 0.001), particularly in younger patients. High FUBP1 expression was associated with improved overall survival in univariate analysis (HR = 0.68, P = 0.028), yet this association was not maintained as an independent prognostic factor after adjustment for other clinical covariates (HR = 0.722, P = 0.098). Immunohistochemistry results from the independent cohort confirmed upregulated FUBP1 protein in 90% of CRC specimens. Single-cell analysis revealed that FUBP1-high cell clusters exhibited markedly reduced immune cell infiltration (35.97%vs 62.96%, P < 0.001), indicating an immunosuppressive "cold" tumor microenvironment. Tumors with high FUBP1 expression also displayed elevated PD-L1, PD-1, and CTLA4 expression, lower half-maximal inhibitory concentration (IC50) values for oxaliplatin, irinotecan, and 5-fluorouracil, and higher Immune Phenotype Score (IPS) for anti-PD-1 monotherapy or combined anti-CTLA-4 immunotherapy. FUBP1 expression was correlated with increased expression of MYC, TP53, and their downstream target genes (CCND1, CDK4, BAX, CDKN1A).
CONCLUSION
FUBP1 is highly expressed in CRC and associated with an immunosuppressive "cold" tumor microenvironment characterized by decreased immune cell infiltration, while it correlates with favorable chemotherapeutic sensitivity. FUBP1 may serve as a potential predictive biomarker for responses to chemotherapy and immunotherapy, rather than an independent prognostic indicator for survival. Its linkage to MYC and TP53 signaling pathways warrants further mechanistic investigation.
Zhen-Xiang Li, Yan-Fang Zhao, Yan-Li Si et al.· Cancer Treatment and Researc...· 0 citations
Breast cancer (BC) is a disease that occurs relatively frequently, and its prognosis and treatment outcomes are not optimal at present. Identifying novel BC biomarkers and therapeutic targets is key. DEAH-box helicase 15 (DHX15) is an RNA helicase that exhibits enhanced activity and is closely associated with tumorigenic potential. Alternative splicing is widely dysregulated in BC. However, the biological function of DHX15 in BC, in addition to its underlying molecular mechanisms, remain unclear. DHX15, a key RNA helicase involved in splicing regulation, was therefore selected to explore whether it modulates the malignant progression of BC. The present study therefore analyzed the DHX15 expression profile in BC using the Tumor Immune Estimation Resource database. Kaplan-Meier plotter database was utilized to investigate the prognostic value of DHX15 in BC. The Cancer Genome Atlas-BRCA database was utilized to investigate the association between DHX15 and immune infiltration, as well as the expression of immune biomarkers, within the tumor microenvironment. The potential biological functions of DHX15 in BC were also investigated using Gene Ontology (GO) enrichment analysis, Kyoto encyclopedia of genes and genomes pathway analysis (KEGG) and single-cell functional analysis. GO and KEGG enrichment analyses were performed via the GSEA module embedded in the LinkedOmics database. Single-cell functional analysis was performed using the Human Proteome Atlas database and the CancerSEA database. Concurrently, the expression and function of DHX15 in BC was validated. MDA-MB-231 cells were transfected with a DHX15 knockdown plasmid and MCF-7 cells with an overexpression plasmid, and Transwell assays, plate cloning and scratch assays were performed on the established cell lines. The present findings revealed that the DHX15 expression levels in BC were notably higher compared with those in normal tissues. Furthermore, the expression of DHX15 was associated with immune checkpoints (such as PDCD1, LAG3 and GZMB) and immune cell infiltration (such as T helper cells and central memory T cells) in BC, as determined by single-sample Gene Set Enrichment Analysis and CIBERSORT analyses. In vitro experiments suggested that inhibiting DHX15 notably suppressed the migration, invasion and proliferation of MDA-MB-231 cells. Collectively, these findings suggest that the high expression of DHX15 in BC is associated with worse prognosis and immune cell infiltration, potentially by functionally promoting tumor cell proliferation, migration and invasion.
Fan Li, Qin Yue, Jing Li· Oncology Letters· 0 citations
BACKGROUND
Breast cancer (BC), the most widespread malignancy in women globally, is characterized by complex and heterogeneous mechanisms. Lectin, mannose binding 2 (LMAN2), a potential oncogene highly expressed in BC, is linked to poor prognosis. The transcription factor forkhead box protein A1 (FOXA1) is often overexpressed in BC and tied to malignant phenotypes, but how it regulates LMAN2 to influence BC progression remains unclear.
METHODS
LMAN2 expression in BC and its association with patient prognosis were analyzed via the GEPIA database. mRNA and protein levels were detected by qRT-PCR and Western blot. Cell proliferation, angiogenesis, invasion/migration, and apoptosis were evaluated using EdU, tube formation assay, Transwell, and flow cytometry. The ferroptosis status of cells was assessed by detecting ferroptosis-related indicators. The transcriptional regulatory effect of FOXA1 on LMAN2 was verified using JASPAR database, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays. The in vivo effect of the FOXA1/LMAN2 axis on BC growth was validated using a nude mouse xenograft model, and related protein expression was detected by immunohistochemistry (IHC).
RESULTS
LMAN2 was upregulated in BC, with high expression linked to poor survival. Silencing LMAN2 was associated with reduced BC cell proliferation, migration, invasion, and angiogenesis, concomitant with increased ferroptosis and apoptosis. FOXA1 binding sites were identified in the LMAN2 promoter; FOXA1 directly bound to this region to enhance LMAN2 transcription, and FOXA1 knockdown reduced LMAN2 expression. FOXA1 overexpression enhanced BC cell malignancy and suppressed ferroptosis, with these effects reversed by concurrent LMAN2 silencing. In vivo, FOXA1 knockdown restrained xenograft tumor growth, and this effect was reversed by concurrent LMAN2 overexpression.
CONCLUSION
FOXA1 bound to the LMAN2 promoter to enhance its transcription, thereby promoting BC progression at least partially through ferroptosis suppression and malignant phenotype induction.
Zhi-Tao Zhang, Shaoyu Wang, Haifeng Sun et al.· Tissue & Cell· 0 citations
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.
Hong-Rong Wu, Liang-Li Hong· Current Medicinal Chemistry· 0 citations
Colorectal cancer (CRC) is the second cause of cancer‐related deaths worldwide. Although ubiquitin‐conjugating enzyme 9 (UBC9) expression has been implicated in a variety of malignancies, its precise role in CRC remains poorly understood. Also Phosphatidylinositol 3‐kinase (PI3K) signaling is known to enhance cellular proliferation in various cancers. This study aims to investigate the expression of UBC9 and PI3K in CRC, prognostic and predictive significance, and association with patients' survival. A total of 140 archival samples of CRC, 70 normal colonic tissue, and 40 metastatic lymph nodes were included. Immunohistochemistry was done for UBC9 and PI3K antibodies, and appropriate statistical analysis of results was performed. UBC9 and PI3K are highly expressed in tumor cells, where co‐high expression is significantly associated with high grade, advanced stage, high lymph node ratio (LNR), lympho‐vascular invasion (LVI), low tumor infiltration lymphocytes (TILs), chemo‐resistance, and positive KRAS mutation, with the poorest median survival (17 months) in patients. Significant positive association was revealed between both molecules in metastatic lymph nodes. UBC9 and PI3K are related to CRC poor survival and resistance to treatment. A potential combined role of both molecules in colorectal carcinogenesis could be found.
Ola Nasser, A. Rabea, Reham Diaa· Acta Pathologica, Microbiolo...· 0 citations
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