Oncology Research最新文献

Background: Aberrant expression of transcription factors (TFs) is a key mechanism mediating tumor immune escape and therapeutic resistance. The involvement of E26 transformation-specific (ETS) family of TFs in immune regulation is not fully understood. The study aimed to elucidate the function of E-twenty-six variant 4 (ETV4) in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.

Methods: The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma (HCC). Single-cell RNA sequencing (scRNA-seq) was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment. Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth. The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1 (PD-1) blockade therapy was evaluated.

Results: TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups. In melanoma, the polyoma enhancer activator 3 (PEA3) subfamily, particularly ETV4 and ETV5, showed a negative correlation with immune infiltration. scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions. Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1 (PD-L1). In immunocompetent murine models, ETV4 downregulation significantly suppressed tumor growth. Furthermore, high ETV4 expression correlated with poor responses to anti-PD-1 therapy.

Conclusion: Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression. ETV4 may act as a predictive biomarker for immunotherapy outcomes.

[This retracts the article DOI: 10.3727/096504017X14850134190255.].

Background: Long non-coding RNAs (lncRNAs) act as epigenetic regulators for tumor hallmarks. This investigation sought to probe the carcinogenic trait of PAN3-AS1 across pan-cancer comprehensively.

Methods: We studied the diagnostic and prognostic features and the immune landscape of PAN3-AS1 across pan-cancer by bioinformatics approaches. The hierarchical regulatory networks governing PAN3-AS1 expression in colon cancer were explored via chromatin immunoprecipitation, luciferase activity assays, and RNA immunoprecipitation, etc. We screened drugs sensitive to WAP four-disulfide core domain 13 (WFDC13) by virtual screening and molecular docking.

Results: Single-cell transcriptomics demonstrated that a variety of immune populations abnormally expressed PAN3-AS1 beyond tumor cells. Integration of data from multiple databases revealed that PAN3-AS1 was highly expressed and associated with a bad prognosis in various malignancies. Notably, PAN3-AS1 expression was correlated with a suppressive immune microenvironment. Moreover, we observed poor immunotherapy efficacy when PAN3-AS1 was highly expressed in melanoma. In vitro assays and functional enrichment analysis revealed that PAN3-AS1 was associated with cell proliferation and the immune response in colon cancer. Our experiments confirmed that PAN3-AS1 facilitated WFDC13 expression through competitive binding to hsa-miR-423-5p in colon cancer. Moreover, the present paper illustrated that enhancer activity exerts an important modulatory ability for PAN3-AS1 expression.

Conclusion: In short, PAN3-AS1 is a valuable biomarker for diagnosis and prognosis. PAN3-AS1 exhibits linkage to a cold tumor immune microenvironment (TME) and forecasts durable benefit from immunotherapy. Addressing the PAN3-AS1/miR-423-5p/WFDC13 axis might provide a novel option for improving immunotherapy efficacy in colon cancer.

Male breast cancer (MBC) is rare, representing 0.5%-1% of all breast cancers, but its incidence is increasing due to improved diagnostics and awareness. MBC typically presents in older men, is human epidermal growth factor receptor 2 (HER2)-negative and estrogen receptor (ER)-positive, and lacks routine screening, leading to delayed diagnosis and advanced disease. Major risk factors include hormonal imbalance, radiation exposure, obesity, alcohol use, and Breast Cancer Gene 1 and 2 (BRCA1/2) mutations. Clinically, it may resemble gynecomastia but usually appears as a unilateral, painless mass or nipple discharge. Advances in imaging and liquid biopsy have enhanced early detection. Molecular mechanisms involve hormonal signaling, HER2/epidermal growth factor receptor (EGFR) pathways, tumor suppressor gene alterations, and epigenetic changes. While standard treatments mirror those for female breast cancer, emerging options such as cyclin-dependent kinase 4 and 6 (CDK4/6), and poly(ADP-ribose) polymerase (PARP) inhibitors, immunotherapy, and precision medicine are reshaping management. Incorporating artificial intelligence, molecular profiling, and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.

This narrative review examines recent advances in salivary biomarkers for oral squamous cell carcinoma (OSCC), a major subtype of oral cancer with persistently low five-year survival rates due to delayed diagnosis. Saliva has emerged as a noninvasive diagnostic medium capable of reflecting both local tumor activity and systemic physiological changes. Various salivary biomarkers, including microRNAs, cytokines, proteins, metabolites, and exosomes, have been linked to oncogenic signaling pathways involved in tumor progression, immune modulation, and therapeutic resistance. Advances in quantitative polymerase chain reaction, mass spectrometry, and next-generation sequencing have enabled comprehensive biomarker profiling, while point-of-care detection systems and saliva-based omics platforms are accelerating clinical translation. Remaining challenges include variability in salivary composition, lack of standardized collection protocols, and insufficient validation across large patient cohorts. This review highlights the mechanistic relevance, diagnostic potential, and translational challenges of salivary biomarkers in OSCC.

Objectives: The mechanism by which specific tumor subsets in colorectal cancer (CRC) use alternative metabolic pathways, particularly those modulated by hypoxia and fructose, to alter the tumor microenvironment (TME) remains unclear. This study aimed to identify these malignant subpopulations and characterize their intercellular signaling networks and spatial organization through an integrative multi-omics approach.

Methods: Leveraging bulk datasets, single-cell RNA sequencing, and integrative spatial transcriptomics, we developed a prognostic model based on hypoxia-and fructose metabolism-related genes (HFGs) to delineate tumor cell subpopulations and their intercellular signaling networks.

Results: We identified a specific subset of stanniocalcin-2 positive (STC2+) malignant cells spatially enriched within tumor regions and strongly associated with poor prognosis. This subset served as a key signaling hub in the TME, exhibiting increased epithelial-mesenchymal transition activity. STC2+ cells engage in two spatially organized ligand-receptor interactions: the growth differentiation factor 15 (GDF15)-transforming growth factor beta receptor 2 (TGFBR2) pathway targeting endothelial cells and the migration inhibitory factor (MIF)-(cluster of differentiation 74 [CD74]+C-X-C motif chemokine receptor 4 [CXCR4]) pathway targeting macrophages.

Conclusion: This study identified a malignant cell state in CRC that is metabolically defined and spatially limited, including liver metastases, and is characterized by elevated STC2 expression and active immune-stromal interactions. Given the interplay between metabolic reprogramming and TME remodeling, STC2+ malignant cells are a functionally significant subpopulation and a potential therapeutic target.

Objectives: Chromobox 4 (CBX4), a polycomb protein family member linked to tumor pathogenesis via dysregulation, has an incompletely defined role in gastric cancer (GC). The study aimed to investigate the role and mechanism of CBX4 in GC progression and evaluate its potential as a therapeutic target.

Methods: CBX4 expression was assessed in GC tissues vs. adjacent non-cancerous tissues and in GC cell lines vs. normal gastric mucosal epithelial cells. Clinicopathological correlations were analyzed. Functional impacts of CBX4 were determined using knockdown and overexpression models in vitro (cell proliferation, migration, invasion) and in vivo (xenograft tumorigenesis in nude mice). Mechanistic studies evaluated β-catenin levels (total and nuclear) and transcriptional activity following CBX4 modulation. The functional dependency on Wnt/β-catenin signaling was tested using the pharmacological inhibitor XAV939 in CBX4-overexpressing cells.

Results: CBX4 expression was significantly upregulated in GC tissues and cell lines. Elevated CBX4 levels strongly correlated with aggressive tumor characteristics, including larger tumor size, lymph node metastasis, and advanced Tumor, Node, Metastasis (TNM) stage. Functionally, CBX4 knockdown suppressed GC cell proliferation, migration, invasion in vitro, and tumorigenesis in vivo. Conversely, CBX4 overexpression enhanced these malignant traits. Mechanistically, CBX4 depletion reduced total and nuclear β-catenin levels and inhibited its transcriptional activity, while CBX4 overexpression had the opposite effect. Critically, XAV939-mediated inhibition of Wnt/β-catenin signaling attenuated the oncogenic effects induced by CBX4 overexpression.

Conclusion: CBX4 upregulation promotes GC progression via β-catenin signaling activation. The CBX4/β-catenin axis emerges as a promising therapeutic target, offering potential for the development of precision treatment strategies in GC management.

[This retracts the article DOI: 10.3727/096504017X14850151453092.].

The last research focuses on the role of exosomes in cancer treatment. Exosomes are extracellular vesicles. They can be secreted by cancer cells, and they can modulate chemotherapy sensitivity. Determining exosomal content opens the possibility for guiding treatment strategies for cancer diseases. Exosomal microRNA are considered one of the prime candidates for exosomal biomarkers. Exosomal circular RNAs represent excellent biomarkers for liquid biopsy because of their stability in many types of cancer. Exosomal proteins remain reliable biomarkers also. Exosomes have emerged as promising therapeutic candidates. Their biological properties render them ideal vectors for drug delivery. Genetic modification of exosomes is an effective way to deliver material capable of modulating cellular pathways involved in drug resistance. Furthermore, exosomes have been explored as carriers for metal-chelating agents. Integrating exosome-based therapies with traditional anticancer agents aims to exploit the natural targeting abilities of exosomes to enhance drug delivery. Despite the dynamic development of this field, many mechanisms of exosome action remain incompletely understood. Therefore, it is necessary to conduct further studies that will allow for a better understanding of their role in the process of resistance and will enable the development of effective therapeutic strategies.

Objective: Triple-negative breast cancer (TNBC) is highly aggressive and lacks an effective targeted therapy. This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2 (ZMIZ2) and minichromosome maintenance complex component 3 (MCM3) in TNBC progression.

Methods: The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated. In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors. The regulatory relationship between ZMIZ2 and MCM3 was also explored. Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC.

Results: High ZMIZ2 expression levels were associated with the malignant degree of TNBC. ZMIZ2 overexpression promoted TNBC cell proliferation, migration, and invasion; inhibited apoptosis; and induced G1 phase cell cycle arrest, whereas knockdown of ZMIZ2 had the opposite effect. ZMIZ2 directly targeted and positively regulated MCM3 expression. MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo. High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC. The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways, such as the mitogen-activated protein kinase (MAPK), mechanistic target of rapamycin (mTOR), Wnt, and Ras signaling pathways, as verified by The Cancer Genome Atlas data.

Conclusions: ZMIZ2 and MCM3 were highly expressed in TNBC. ZMIZ2 promoted the development by positively regulating MCM3 expression. Key pathways, such as the Ras/MAPK, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mTOR, and Wnt signaling pathways, may be key downstream mechanisms.