Oncology Research最新文献

Objectives: Gastric cancer (GC) remains a major global health concern, and Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1), a regulatory subunit of the PI3K signaling pathway, may play a critical yet underexplored role in GC progression. This study aimed to investigate the prognostic significance of PIK3R1 in GC and its association with the tumor immune microenvironment.

Methods: PIK3R1 expression and its clinical relevance were analyzed using datasets from GC patients who underwent gastrectomy, including cohorts from The Cancer Genome Atlas (TCGA) and the Sun Yat-sen University Cancer Center (SYSUCC). Prognostic models integrating PIK3R1 expression with clinical parameters were constructed for both cohorts. The immune microenvironment associated with PIK3R1 expression was assessed through immunohistochemistry and single-cell RNA sequencing. In vitro assays were conducted to evaluate the effects of PIK3R1 on GC cell proliferation and migration.

Results: PIK3R1 was significantly overexpressed in GC tissues and was closely associated with aggressive tumor characteristics and poor clinical outcomes. A nomogram combining PIK3R1 expression with clinicopathological features effectively predicted patient prognosis. Knockdown of PIK3R1 in GC cells reduced proliferation and migration in vitro. Immunological profiling revealed that high PIK3R1 expression correlated with increased infiltration of forkhead box protein P3 (Foxp3⁺) and cluster of differentiation 73 (CD73⁺) T cells. Patients with low PIK3R1 expression and low CD73⁺ T cell infiltration had significantly better survival.

Conclusions: PIK3R1 overexpression is linked to poor prognosis in GC and influences the extent of immune cell infiltration within the tumor microenvironment. A novel prognostic model integrating PIK3R1 and CD73 expression with clinical parameters was established to stratify GC patients into distinct risk groups, offering potential value for personalized therapeutic strategies.

Prostate cancer (PCa) remains a major cause of cancer-related mortality in men, largely due to therapy resistance and metastatic progression. Increasing evidence highlights the tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), as a critical determinant of disease behavior. CAFs constitute a heterogeneous population originating from fibroblasts, mesenchymal stem cells, endothelial cells, epithelial cells undergoing epithelial-mesenchymal transition (EMT), and adipose tissue. Through dynamic crosstalk with tumor, immune, endothelial, and adipocyte compartments, CAFs orchestrate oncogenic processes including tumor proliferation, invasion, immune evasion, extracellular matrix remodeling, angiogenesis, and metabolic reprogramming. This review comprehensively summarizes the cellular origins, phenotypic and functional heterogeneity, and spatial distribution of CAFs within the prostate TME. We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance, and critically evaluate emerging strategies to therapeutically target CAF-mediated signaling, metabolic, and immune pathways. By integrating recent advances from single-cell and spatial transcriptomics (ST), our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.

Parasitic infections are increasingly recognized as contributors to cancer development, yet the underlying oncogenic mechanisms remain insufficiently understood. Growing evidence from molecular oncology, immunology, and microbiome research suggests that chronic parasitic infections may drive tumorigenesis through sustained inflammation, deregulated signaling pathways, genomic instability, and the release of parasite-derived exosomes that reshape the tumor microenvironment. These insights underscore the need to integrate parasitology with cancer biology to understand infection-associated malignancies better. The aim of this narrative review is to synthesize current knowledge on how selected parasites contribute to cancer development and to highlight emerging therapeutic and diagnostic opportunities. We examine pathogens such as Schistosoma haematobium, Opisthorchis viverrini, Toxoplasma gondii, Plasmodium falciparum, and Leishmania spp., detailing their roles in chronic inflammation, immune modulation, and interactions with tumor-associated immune cells. The review further discusses parasite-induced immunosuppression, coinfections, and their cumulative impact on cancer risk. Additionally, we explore novel therapeutic approaches, including pathway inhibitors, epigenetic drugs, microbiome modulation, and engineered parasites. Future perspectives emphasize parasite-based immunotherapies, long-term epigenetic consequences of infection, and AI-driven multi-omics strategies for identifying oncogenic signatures. This review integrates advances from parasitology and oncology to provide new insights into biomarkers, targeted therapies, and mechanisms of infection-induced tumorigenesis. The literature search covered studies indexed in PubMed, Scopus, and Web of Science up to July 2025.

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.