J Cancer [JOURNAL]
Sun
200 papers
Prognostic significance and potential association between ALDOA and ENO1 in gastric cancer.
Wang X, Lu Y, Cheng Z … +2 more , Yao Y, Shao X
J Cancer · 2025 · PMID 41049005 · Full text
Gastric cancer (GC) is one of the most common malignant tumors and a leading cause of cancer-related death worldwide. Although advances in surgical techniques and novel treatment techniques such as immunotherapy have imp...
Gastric cancer (GC) is one of the most common malignant tumors and a leading cause of cancer-related death worldwide. Although advances in surgical techniques and novel treatment techniques such as immunotherapy have improved the prognosis of many tumors, the effectiveness of treatment for advanced GC patients is still limited. Immunohistochemistry (IHC) staining analysis was conducted to compare the expression of ALDOA and ENO1 in GC tissues and adjacent normal tissues, complemented by bioinformatics analysis using GEPIA, LinkedOmics, and TIMER databases to explore their association with glycolysis and immune cell infiltration. A survival prediction nomogram was constructed based on Cox proportional hazard model data to evaluate prognostic significance. In this study, through IHC staining analysis, it was observed that the expression levels of ALDOA and ENO1 in GC tissues were significantly higher than those in adjacent normal tissues. Moreover, the aberrant expression of ALDOA/ENO1 was associated with a poor prognosis in GC patients. Bioinformatics analysis revealed a positive correlation between ALDOA and ENO1 expression, both intricately associated with glycolysis pathway activation. A survival prediction nomogram, constructed based on the univariate analysis of data from the Cox proportional hazard model, demonstrated that the expression of ALDOA and ENO1 significantly impacts the prognosis of GC patients. ALDOA/ENO1 may play a crucial role in GC, which may potentially offer new perspectives and directions for the development of targeted therapies specifically designed for GC patients.
Inflammatory Bowel Disease Mediates the Causal Relationship Between Gut Microbiota and Colorectal Cancer: Identification of Therapeutic Targets and Predictive Modeling.
Wang JB, Wu ZG, Bi GW … +3 more , Li Y, Yao ZW, Yu YB
J Cancer · 2025 · PMID 41049004 · Full text
Colorectal cancer (CRC) is the second leading cause of cancer-related mortality. Given its established associations with gut microbiota and inflammatory bowel disease (IBD), elucidating their relationships and developing...
Colorectal cancer (CRC) is the second leading cause of cancer-related mortality. Given its established associations with gut microbiota and inflammatory bowel disease (IBD), elucidating their relationships and developing predictive models are critical for early detection and therapy. Using Mendelian randomization (MR), we integrated data from the MiBioGen Consortium and multiple genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) associated with gut microbiota were mapped to genes, followed by gene selection via least absolute shrinkage and selection operator (LASSO) regression. Transcriptome analyses identified differential gene expressions and immune cell infiltration patterns. Six machine learning models were integrated through soft voting to predict CRC risk, validated by single-cell sequencing analysis. Mediation MR identified 12 gut microbial taxa causally associated with CRC, mediated partially by IBD. SNP mapping and expression analysis highlighted eight CRC-associated genes, five of which (FAM120A, GBE1, MCM6, MSRA, ZDHHC4) were further underscored by drug target MR and summary-data-based MR (SMR). Transcriptomics implicated dysregulation in the neuroactive ligand-receptor interactions and the G2/M DNA checkpoint pathway. Immune infiltration analysis demonstrated elevated CD4⁺ T cells and M0 macrophages in the high-LASSO score group. Integrated machine learning models built using the five key genes achieved robust predictive performance. Single-cell sequencing analysis confirmed gene expression patterns. By integrating mediation MR, transcriptomics, and machine learning, this study demonstrated causal relationships between specific gut microbiota and CRC, with IBD as a mediator. We identified potential therapeutic targets and developed robust predictive models, providing crucial insights into the pathogenesis and clinical detection of CRC.
Novel Tri-Specific Immuno-Modulatory Antibody Combined with HDACi to Potentiate T Cell Activation and Anti-Tumor Efficacy.
Gou Y, Yuan X, Fan D … +2 more , Yang Y, Yuan H
J Cancer · 2025 · PMID 41049003 · Full text
Although blinatumomab, a bispecific T-cell engager, has exhibited promising clinical outcomes in the treatment of B-precursor acute lymphoblastic leukemia (B-ALL) and B cell non-Hodgkin's lymphoma (B-NHL), it still has s...
Although blinatumomab, a bispecific T-cell engager, has exhibited promising clinical outcomes in the treatment of B-precursor acute lymphoblastic leukemia (B-ALL) and B cell non-Hodgkin's lymphoma (B-NHL), it still has some limitations due to CD19-negative relapse and an immunosuppressive phenotype. Epigenetic modulators have the potential to influence the tumor microenvironment (TME) and immune cycle in various ways. Combining multiple drugs is a trend in tumor treatment. In this article, we generated a novel tri‑specific antibody, called CiTE (CD3-BAFF-R-PD-L1), which is composed of a CD3 binding Fab frame, a BAFF-R binding scFv, and an additional scFv derived from PD‑L1. The cytotoxicity of T cells induced by CiTE (CD3-BAFF-R-PD-L1) was detected in combination with Chidamide. The purified CiTE (CD3-BAFF-R-PD-L1) exhibited high binding capability for CD3-positive cells, BAFF-R-positive cells, and PD-L1-positive cells. Consequently, specific lysis towards BAFF-R-positive cell lines were induced by CiTE (CD3-BAFF-R-PD-L1) in the presence of T cells. We also confirmed that Chidamide could enhance T-cell mediated lysis by upregulating antigen strength on tumor cells and altering the TME by increasing the expression of T cell-attracting chemokines and costimulatory molecules. The novel tri-specific antibody combined with Chidamide holds promise as a safe and effective drug for the treatment of B-cell malignancies, due to its integration of three sections targeting different molecules into one compound.
Insight into the Role of the BCL6B Gene in Biological Functions and Disease Progression.
Pan Y, Li Y
J Cancer · 2025 · PMID 41049002 · Full text
The B-cell CLL/lymphoma 6B (BCL6B) gene, a homolog of , belongs to the ZBTB (zinc finger and BTB domain-containing) protein family and functions as a transcriptional repressor involved in gene regulation and cellular pro...
The B-cell CLL/lymphoma 6B (BCL6B) gene, a homolog of , belongs to the ZBTB (zinc finger and BTB domain-containing) protein family and functions as a transcriptional repressor involved in gene regulation and cellular proliferation. In recent years, BCL6B has garnered increasing attention due to its critical involvement in various biological processes, including tumor suppression, immune modulation, stem cell maintenance, and angiogenesis. Moreover, its dysregulation, often through epigenetic modifications such as promoter hypermethylation, has been implicated in the pathogenesis of several malignancies and immune-related disorders. This review provides a comprehensive overview of BCL6B's molecular functions, its roles in human disease, and emerging research advances, highlighting its potential as both a diagnostic biomarker and a therapeutic target.
Robust machine-learning based prognostic index using fatty acid metabolism genes predicts prognosis and therapy responses in glioblastoma.
Zhao E, Wang Z, Tang L … +7 more , Zhang L, He L, Li M, Ge X, Shi Z, Qian X, Cao R
J Cancer · 2025 · PMID 41049001 · Full text
: Glioblastoma (GBM) is the most prevalent and aggressive type of primary brain tumor in adults. Fatty acid metabolism plays a crucial role in promoting tumorigenesis, disease progression, and therapeutic resistance thro...
: Glioblastoma (GBM) is the most prevalent and aggressive type of primary brain tumor in adults. Fatty acid metabolism plays a crucial role in promoting tumorigenesis, disease progression, and therapeutic resistance through the regulation of lipid synthesis, storage, and catabolism. However, its potential for predicting both prognosis and treatment response in glioblastoma is unexplored. : We systematically compiled fatty acid metabolism-related genes (FAMGs) from published literature and databases. A fatty acid metabolism signature (FAMS) was developed using a machine learning-based framework. The predictive performance of the FAMS was rigorously validated across multiple independent cohorts. Additionally, we investigated the associations between FAMS and clinical characteristics, mutation profiles, tumor microenvironment features, and biological functions. : Our analysis revealed distinct FAMGs expression patterns in patients with GBM, which correlated with varying survival outcomes. Leveraging a robust machine learning framework, we established a fatty acid metabolism-based prognostic model. The FAMS emerged as an independent predictor of overall survival and other survival endpoints. Patients with lower FAMS exhibited enrichment in mitosis- and DNA repair-related pathways, which is linked to better survival. Conversely, higher FAMS scores were associated with enhanced immune activation, cellular proliferation, and chemotaxis, suggesting a greater likelihood of benefitting from immunotherapy. : We developed a reliable fatty acid metabolism signature capable of stratifying GBM patients on the basis of prognosis. The FAMS serves as an independent prognostic indicator and may offer clinical utility in guiding personalized treatment strategies for patients with GBM.
HKDC1 in Cancer: Mechanisms, Clinical Applications, and Future.
Luo X, Peng M, Wang Z … +2 more , Wu N, Wang Y
J Cancer · 2025 · PMID 41049000 · Full text
Cancer incidence and mortality rates are on the rise, with ovarian cancer being a significant concern globally. HKDC1 is identified as a crucial protein involved in cancer metabolism, particularly in lung, liver, colorec...
Cancer incidence and mortality rates are on the rise, with ovarian cancer being a significant concern globally. HKDC1 is identified as a crucial protein involved in cancer metabolism, particularly in lung, liver, colorectal, and gastric cancers. Its upregulation correlates with poor clinical outcomes and promotes tumor progression through various mechanisms, including enhanced glycolysis and immune evasion. The exploration of HKDC1's role in cancer offers potential for new therapeutic strategies and biomarkers in cancer treatment.
Epigenetic regulation espeically histone modifications in breast cancer: A viable and emerging targeted therapeutic strategy.
Zhou Y, Liu H, Hong W … +6 more , Su H, Mu Y, Cheng Y, Wu C, Meng X, Qian D
J Cancer · 2025 · PMID 41048999 · Full text
Epigenetic regulation, encompassing DNA methylation, histone modifications, and non-coding RNA activities, is a crucial mechanism through which gene expression is modified without corresponding changes in genomic DNA seq...
Epigenetic regulation, encompassing DNA methylation, histone modifications, and non-coding RNA activities, is a crucial mechanism through which gene expression is modified without corresponding changes in genomic DNA sequences. Dysregulation of these mechanisms can lead to histone and DNA modifications that either suppress or enhance the expression of disease progression-related genes. Among these regulatory processes, histone modifications are particularly significant, as they contribute to genomic stability, DNA repair, and chromatin dynamics, all of which influence breast cancer initiation and progression. This review offers a detailed analysis of the current state of research centered on epigenetic regulatory factors, with a particular focus on the role that histone modifications play in the treatment of breast cancer. It also examines the interplay between epigenetic modifications and the effectiveness of radiotherapy and chemotherapy when treating breast cancer. Lastly, this article explores the potential of epigenetic regulatory factors as viable targets for the future design of new anticancer therapies.
Pseudouridylation-Related Genes Predict Prognosis and Therapeutic Response in Hepatocellular Carcinoma Patients.
Lan C, Gao D, Wei Y … +7 more , Huang H, Lv X, Zhou X, Qin W, Liao X, Zhu G, Peng T
J Cancer · 2025 · PMID 41048998 · Full text
Emerging evidence has demonstrated that pseudouridylation regulates mRNA translation and gene expression, yet its molecular characteristics in hepatocellular carcinoma (HCC) remain unknown. Using public databases, we dev...
Emerging evidence has demonstrated that pseudouridylation regulates mRNA translation and gene expression, yet its molecular characteristics in hepatocellular carcinoma (HCC) remain unknown. Using public databases, we developed pseudouridylation-related molecular subtype and risk score model to assess HCC patient prognosis and disclose their clinical feature, molecular mechanism and immune landscape. Furthermore, quantitative polymerase chain reaction (qPCR) was performed to verify the expression of RDM1, CDCA3 and FLVCR1. Specifically, functional enrichment analysis revealed pseudouridylation-related genes (PRGs) predominantly regulate transcriptional and translational regulation. Prognostic PRGs stratified HCC into two distinct subtypes, the cluster 1 had a poor prognosis and was characterized by high alpha fetoprotein level, poor differentiation, advanced tumor stage, large tumor size, frequent TP53 mutation, up-regulation of cell cycle- and mitosis-associated genes, which was similar to the aggressive proliferation subtype of HCC. In contrast, the cluster 2 exhibited good prognosis and increased infiltration of immune cells, resembling the non-proliferation subtype of HCC, and suggesting its potential responsiveness to immunotherapy. Survival analysis discovered that the risk score model served as an independent prognostic factor, with high-risk group exhibiting significantly shorter overall survival and recurrence-free survival than low-risk group. Notably, receiver operating characteristic analysis revealed that the risk model had a powerful predictive performance for 1- and 3- year survival (AUC=0.806). In addition, functional enrichment analysis suggested that upregulated genes of high-risk group displayed an enrichment of cell cycle progression, mitotic division, and some oncogenic signaling pathways (PLK1, FOXM1, and p53 signaling pathways). qPCR experiment confirmed the significant overexpression of RDM1, CDCA3, and FLVCR1 in HCC tissues, being consistent with public database analysis. In conclusion, pseudouridylation related-molecular subtype and risk model may effectively predict the prognosis and therapeutic response of HCC.
Identification of Plasma Protein Biomarkers and Drug Targets for Hematologic Malignancies by Proteome-wide Mendelian Randomization.
Pan T, Zhang J, Wang X … +1 more , Song Y
J Cancer · 2025 · PMID 41048997 · Full text
It has been reported that the proteome in blood was an important source for biomarker and therapeutic target discovery. However, up to now, few proteomes have been identified with the risk of hematologic malignancies. G...
It has been reported that the proteome in blood was an important source for biomarker and therapeutic target discovery. However, up to now, few proteomes have been identified with the risk of hematologic malignancies. Genome-wide association studies (GWASs) including 3,083 plasma proteins are based on data from 54,219 people in the UK Biobank Pharma Proteomics Project (UKB-PPP) and 35,559 individuals from Iceland (deCODE). Genetic correlations with 33 hematologic malignancies were derived from the FinnGen cohort and the UK Biobank Data. Further studies, including Bayesian colocalization, protein-protein interaction assessment, pathway enrichment analysis, and drug target evaluation, were performed to enhance knowledge and identify prospective therapeutic targets for 33 hematologic cancers. : Our study indicated that 86 potential plasma proteins may have a substantial causal association with the incidence of 33 hematological tumors, such as BCL2, NFKB1, PARP1, and TNFRSF14. There are 18 proteins with strong evidence of genetic co-localization and 9 proteins with moderate support from colocalization analysis. Out of the 86 proteins, 51 have druggable targets, and 26 were identified as targets for current or prospective pharmaceuticals. : Our research revealed numerous significant proteins linked to the likelihood of hematologic malignancies. It may elucidate protein-mediated processes of hematological tumors and provide prospective treatment options for individuals with these conditions.
CD40LG Downregulation in Lung Adenocarcinoma: A Prognostic Biomarker Linked to Immune Cell Infiltration and Survival Outcomes.
Tang P, Zhang R, Zhang Y … +7 more , Ao Y, Wang Y, Wang G, Wang W, Xu J, Hu F, Zhu G
J Cancer · 2025 · PMID 41048996 · Full text
Lung adenocarcinoma (LUAD) continues to pose a major challenge in cancer treatment, characterized by low survival rates, particularly in metastatic instances. Although immunotherapy has become a common approach for treat...
Lung adenocarcinoma (LUAD) continues to pose a major challenge in cancer treatment, characterized by low survival rates, particularly in metastatic instances. Although immunotherapy has become a common approach for treating LUAD, its success rate is merely 20%, hindered by the absence of effective biomarkers. This limitation is likely influenced by the tumor's immune microenvironment. CD40LG, an important immune molecule, has emerged as a crucial factor in modulating the tumor immune environment and affecting the outcomes of immunotherapy. Nevertheless, its exact mechanisms in LUAD remain unclear, requiring more research. Through a correlation analysis of prognosis and clinical traits across multiple cancers, we determined that CD40LG is significant in LUAD. This role was confirmed using various public datasets. We evaluated CD40LG protein expression in 94 LUAD and nearby non-cancerous tissues via immunohistochemistry. To gauge immune cell infiltration, we employed multiplex immunofluorescence staining on tissue microarrays. Additionally, assays were carried out to explore the effects of CD40LG modulation on the behavior of LUAD cells. Various cancers, including LUAD, exhibited down-regulation of CD40LG, which correlated with a worse prognosis. In LUAD tissues, higher CD40LG expression was associated with longer Progression-Free Survival (PFS) and Overall Survival (OS). Moreover, CD40LG expression negatively correlated with the TNM stage and T stage in LUAD. Elevated CD40LG levels were linked to increased infiltration of CD8+ T cells. studies showed that modulating CD40LG affected LUAD cell metastasis and proliferation. Our study demonstrates the pivotal role of CD40LG in LUAD, proposing its potential utility as a biomarker for prognosis and immunotherapy. The correlation between CD40LG expression, immune cell infiltration, and clinical outcomes emphasizes its importance in tumor-immune dynamics and the efficacy of immunotherapy.
Melittin inhibits osteosarcoma growth and by inactivating the Wnt/β-catenin signaling pathway.
Wang X, Chang J, Sun X … +4 more , Guo S, Li Y, Shi Q, Yang Y
J Cancer · 2025 · PMID 40969387 · Full text
Osteosarcoma is a highly aggressive primary bone tumor that predominantly affects pediatric and adolescent populations. This study aims to explore the therapeutic potential and underlying mechanisms of melittin in treati...
Osteosarcoma is a highly aggressive primary bone tumor that predominantly affects pediatric and adolescent populations. This study aims to explore the therapeutic potential and underlying mechanisms of melittin in treating osteosarcoma both and . Two osteosarcoma cell lines, namely 143B and U-2 OS, were utilized to assess the impact of melittin on cellular proliferation, apoptosis, and cell cycle progression. The effect of melittin on cell viability was evaluated using the CCK-8 assay. Flow cytometry was employed to assess apoptosis and cell cycle progression, while Western blotting analyzed the expression of key proteins, including Cdc-2, c-Myc, and ꞵ-catenin. Specifically, we employed small interfering RNA (siRNA) to selectively knock down the expression of β-catenin in two osteosarcoma cell lines. In studies, tumor growth in nude mice was evaluated through measurements of tumor weight, volume. Additionally, immunohistochemical analysis was performed to assess Ki-67 and active ꞵ-catenin expression in tumor tissues. Melittin induced apoptosis in 143B and U-2 OS osteosarcoma cells in a concentration-dependent manner and caused S-phase cell cycle arrest as the drug concentration increased. Mechanistic investigations revealed that melittin's efficacy was associated with the inactivation of the Wnt/ꞵ-catenin signaling pathway. Specifically, melittin treatment reduced the expression of phosphorylated glycogen synthase kinase-3 beta (p-GSK-3ꞵ) and active ꞵ-catenin. Notably, silencing β-catenin in 143B and U-2 OS osteosarcoma cells significantly enhanced the anti-proliferative and pro-apoptotic effects of melittin. This was evidenced by reduced cell viability and increased apoptosis, thereby further confirming that the anti-tumor efficacy of melittin is dependent on the inhibition of the Wnt/β-catenin signaling pathway. studies confirmed that melittin significantly inhibited the growth of subcutaneously implanted tumors in nude mice. This inhibition was further supported by Ki-67 analyse and H&E staining, while immunohistochemical analysis revealed an obvious reduction in active ꞵ-catenin expression. Our results offer deeper mechanistic insights into the inhibitory impact of melittin on osteosarcoma progression, at least in part by suppressing the Wnt/β-catenin signaling pathway. We expand upon previous research by providing more comprehensive and robust evidences that underscore the potential of melittin as a viable and safe therapeutic agent for osteosarcoma.
Metformin May Improve Intestinal Mucosal Barrier Function and Help Prevent and Reverse Colorectal Cancer in Mice.
Wang R, Xie L, Jiang P … +3 more , Hou Y, Li D, Wang W
J Cancer · 2025 · PMID 40969386 · Full text
Metformin may help prevent the development of colorectal cancer (CRC); however, the mechanisms involved remain unclear. This study aimed to investigate the effects of metformin on CRC onset and progression in a mouse mod...
Metformin may help prevent the development of colorectal cancer (CRC); however, the mechanisms involved remain unclear. This study aimed to investigate the effects of metformin on CRC onset and progression in a mouse model by evaluating any changes to the intestinal mucosal barrier. Sixty BALB/C female mice were randomly divided into control, model, and low-, medium-, and high-dose treatment groups. The CRC models were induced by azoxymethane combined with dextran sulfate sodium. At the time of induction, metformin 125 mg/kg · d, 250 mg/kg · d, and 500 mg/kg · d doses were administered to the low-, medium-, and high-dose groups, respectively. After 14 weeks, no tumor was observed in the control group, and multiple tumors were observed in the four test groups. Fewer tumors emerged in the metformin groups than in the model group. The tumors in the metformin groups were smaller than those in the model group. The expression of ZO-1 and occludin in the colon tissue of mice improved after metformin intervention. We performed intervention studies with varying doses of metformin and a composite disease model (parallel induction of intestinal barrier damage and tumorigenesis) in our experimental design, allowing for novel insights into the temporal effects of metformin. Metformin can improve intestinal mucosal barrier function by restoring the expression of intestinal tight junction proteins in mice and thus may help protect against CRC within a certain dose range.
Association between Tooth Extraction 2 Weeks before Radiotherapy and Osteoradionecrosis in Patients with Advanced Oral and Oropharyngeal Cancer.
Usubuchi M, Kanemura S, Hozawa A … +1 more , Tsuji I
J Cancer · 2025 · PMID 40959112 · Full text
Osteoradionecrosis (ORN) is the most serious late adverse event in standard treatment for locally advanced oral and oropharyngeal cancers. The clinical guidelines recommend dental extractions be completed at least 2 week...
Osteoradionecrosis (ORN) is the most serious late adverse event in standard treatment for locally advanced oral and oropharyngeal cancers. The clinical guidelines recommend dental extractions be completed at least 2 weeks before the start of radiotherapy to reduce the risk of ORN development. However, to what extent tooth extraction 2 weeks before radiotherapy, as recommended by the guidelines, reduces the risk of ORN development is unclear. This study was conducted to examine the association between tooth extraction 2 weeks before radiotherapy and ORN development. The study included patients aged ≥18 years who received chemoradiotherapy with 3-weekly cisplatin or radiotherapy alone for locally advanced oral and oropharyngeal cancer at the head and neck surgery of Miyagi Cancer Center in Japan between 2011 and 2018. Additional oral care (AOC) was provided to the patients between 2011 and 2014; however, because of the downsizing of dentistry in 2015, usual oral care (UOC) was provided to the patients between 2015 and 2018. In the AOC group, all dental infection foci and teeth with poor prognosis in the radiation field were removed 2 weeks before radiotherapy. The cumulative incidence of ORNs was calculated using the Kaplan-Meier method, and multivariate analyses were performed using the Fine-Gray model with death as a competing risk for ORN development. Ninety-three patients were analyzed, 43 in the AOC and 50 in the UOC. The cumulative incidence rate of ORN in the AOC group was lower than that in the UOC group (0.071 vs. 0.415, p < 0.001). The hazard ratio (HR) for the incidence of ORN in the AOC group versus that in the UOC group was lower (HR, 0.108, 95% CI 0.019-0.606). In the subgroup analysis, HRs were lower in the following groups: male (0.062, 0.009-0.425), Eastern Cooperative Oncology Group performance status 0 (0.141, 0.028-0.700), without diabetes (0.135, 0.029-0.635), drinkers with a Sake index of ≥60 (0.033, 0.002-0.518), advanced cancer of clinical stage Ⅳ (0.151, 0.025-0.909), concurrent chemotherapy (0.126, 0.022-0.702), total cisplatin dose of ≥200 mg/m (0.055, 0.007-0.411), and dental risk factors (0.061, 0.007-0.537). This study showed that extraction of at-risk teeth 2 weeks before radiotherapy reduced the risk of ORN development by approximately 90%. However, these results are based on a retrospective observational study conducted at only one center. Thus, future multivariate studies conducted at multiple centers, with death as a competing risk, are needed.
Potential impact of omentin-1 genetic variants on perineural invasion in prostate cancer.
Weng WC, Lin TH, He XY … +8 more , Lin CY, Wu HC, Huang YL, Lai CY, Tsai CH, Fong YC, Yang SF, Tang CH
J Cancer · 2025 · PMID 40959111 · Full text
One of the most prevalent cancers and a major global cause of mortality in men is prostate cancer (PCa). Omentin-1, an adipokine, has been shown to play a protective role by reducing proinflammatory cytokine secretion. T...
One of the most prevalent cancers and a major global cause of mortality in men is prostate cancer (PCa). Omentin-1, an adipokine, has been shown to play a protective role by reducing proinflammatory cytokine secretion. The relationships among carcinogenic lifestyle factors, biochemical recurrence (BCR), polymorphisms, and PCa remain unclear. We investigated the impact of clinicopathological features and four gene variants on PCa risk in 701 Taiwanese male patients with and without BCR. Compared with the TT genotype, the TA+AA genotypes of SNP rs2274907 were associated with a lower risk of perineural invasion. Similarly, the AG+GG genotypes of rs4656959 were associated with a lower risk of perineural invasion compared to the AA genotype. Importantly, PCa patients without BCR exhibited the same effects. Interestingly, the wild-type TT homozygous genotype was associated with significantly lower expression levels compared to the AA genotype of the rs2274907 variant. Additionally, mRNA levels were lower in PCa tissues compared to normal tissues, indicating that omentin-1 acts as a protective factor in PCa.
Spermidine potentiates anti-tumor immune responses and immunotherapy sensitivity in breast cancer.
Yang X, Feng Y, Wang R … +5 more , Zeng X, Gao B, Huang P, Chen H, Zeng W
J Cancer · 2025 · PMID 40959110 · Full text
Spermidine metabolism influences tumor progression and anti-tumor immunity, thereby affecting treatment sensitivity. However, the precise role and therapeutic potential of spermidine in breast cancer remain unclear. Inte...
Spermidine metabolism influences tumor progression and anti-tumor immunity, thereby affecting treatment sensitivity. However, the precise role and therapeutic potential of spermidine in breast cancer remain unclear. Integrated multi-omics analyses (bulk and single-cell RNA sequencing) revealed a significant positive correlation between intratumoral spermidine abundance and immunophenotypic markers of CD8 T cell infiltration and activation (GZMBCD8 T cells). Immunohistochemical and multiplexed immunohistochemistry validation (IHC/mIHC) demonstrated that breast cancer specimens with elevated spermidine production exhibited increased numbers of activated CD8⁺ T cells. Exogenous supplementation with spermidine promoted CD8⁺ T cell activation directly. Furthermore, supplementing spermidine promoted anti-tumor immune responses and enhanced sensitivity to anti-PD-1 immunotherapy combined with chemotherapy. Our findings indicate that boosting spermidine metabolism is a promising strategy to reinvigorate CD8⁺ T cell function and improve the efficacy of checkpoint blockade immunotherapy.
KDM6B enhances anti-PD-L1 immunotherapy efficacy by increasing CD8 T-cell infiltration in colorectal cancer.
Xun J, Liu Z, Liu B … +10 more , Jiang X, Yang H, Liu J, Wang B, Gao R, Zhang A, Wu X, Xi Q, Yu X, Zhang Q
J Cancer · 2025 · PMID 40959109 · Full text
Cytotoxic CD8 T cells play a vital role in its antitumor response, and increasing their infiltration in tumors is an effective strategy for enhancing the efficacy of antitumor immunotherapy. Lysine-specific demethylase 6...
Cytotoxic CD8 T cells play a vital role in its antitumor response, and increasing their infiltration in tumors is an effective strategy for enhancing the efficacy of antitumor immunotherapy. Lysine-specific demethylase 6B (KDM6B) plays a suppressive or oncogenic role in colorectal cancer (CRC). However, the its contribution in CRC immunity remains unclear. The expression of KDM6B was analyzed in CRC using TCGA database and clinical specimens. Its role in tumor growth and metastasis was assessed through in vitro assays and in vivo models, including subcutaneous xenografts and orthotopic liver metastasis mice. CD8 T cell infiltration, recruitment, and activation were assessed via immunohistochemistry, transwell assay, and flow cytometry. The expression of PD-L1 and CD8 T cell-recruiting chemokines CCL5, CXCL9, CXCL10 were detected. GSEA identified KDM6B-regulated signaling pathways. ChIP‒qPCR was used to determined the enrichment level of H3K27me3 on PD-L1, CCL5, CXCL9, and CXCL10 promoters. Finally, the synergistic effect of KDM6B inducer paricalcitol with anti-PD-L1 therapy was investigated using a subcutaneous xenograft mouse model. KDM6B was downregulated in CRC tissues and cells. KDM6B overexpression suppressed CRC proliferation, tumor growth and liver metastasis, while enhancing CD8 T cells infiltration, recruitment, and functional activation. KDM6B upregulated PD-L1 and CCL5, CXCL9, CXCL1 expression in CRC cells. Mechanically, GSEA revealed JAK/STAT pathway enrichment. KDM6B increased p-STAT3 levels and the STAT3 signaling mediated the promoting effect of KDM6B on PD-L1 and chemokines expression. In addition, KDM6B overexpression reduced H3K27me3 enrichment on promoters of PD-L1 and chemokines. Finally, the combination of paricalcitol and anti-PD-L1 antibody enhanced anti-tumor efficacy in CRC mouse model. KDM6B potentially suppresses CRC progression by enhancing CD8 T cell infiltration via dual mechanisms: STAT3-mediated transcriptional activation and H3K27me3 demethylase-dependent epigenetic remodeling of PD-L1 and chemokine genes (CCL5/CXCL9/CXCL10). The synergistic effect of KDM6B inducer paricalcitol with anti-PD-L1 enhances antitumor immunity, supporting its potential combination strategy for CRC treatment.
SETD2 and EZH2: Two epigenetic drivers of prostate cancer.
Wang J, Xiang L, Zhang H … +1 more , Zhang X
J Cancer · 2025 · PMID 40959108 · Full text
Prostate cancer is a prevalent malignancy among men, characterized by complex mechanisms underlying metastasis and treatment resistance. Epigenetic modifications play a crucial role in regulating prostate cancer progress...
Prostate cancer is a prevalent malignancy among men, characterized by complex mechanisms underlying metastasis and treatment resistance. Epigenetic modifications play a crucial role in regulating prostate cancer progression, particularly involving histone methyltransferases such as SET-domain containing 2 (SETD2) and Enhancer of Zeste homolog 2 (EZH2). SETD2 contributes to chromatin stability by catalyzing the trimethylation of histone H3 lysine 36 (H3K36me3), and its downregulation is strongly correlated with increased invasiveness and epithelial-mesenchymal transition in prostate cancer. Conversely, EZH2, the catalytic subunit of Polycomb Repressive Complex 2, mediates gene silencing through H3K27me3 modification and is frequently overexpressed in advanced disease, promoting tumor metastasis and resistance to therapy. Notably, SETD2 regulates EZH2 stability through direct protein interactions, highlighting a coordinated epigenetic regulatory axis. Multi-omics studies have revealed that SETD2 loss induces aberrant DNA methylation and activates oncogenic signaling pathways, whereas EZH2 overexpression cooperates with PI3K-AKT pathway dysregulation to drive castration-resistant prostate cancer. Although inhibitors targeting SETD2 (e.g., EZM0414) and EZH2 (e.g., tazemetostat) demonstrate antitumor activity in preclinical models, their clinical efficacy remains constrained by drug resistance and tumor microenvironment heterogeneity. Emerging evidence suggests that combining epigenetic therapies with immunotherapy may enhance therapeutic outcomes. This review comprehensively systematically examines the molecular mechanisms underlying the SETD2/EZH2 axis in prostate cancer, providing a theoretical foundation for developing precision therapies based on SETD2- or EZH2-mediated epigenetic modifications.
The impact of long non-coding RNA genetic variants on oral cancer progression and clinicopathological characteristics.
Chen PJ, Lin CW, Su CW … +7 more , Wang YC, Wu HH, Chu HJ, Yang SF, Su SC, Huang CC, Chou YE
J Cancer · 2025 · PMID 40959107 · Full text
Oral cancer is the sixth leading cause of cancer-related mortality worldwide. Recent studies suggest that long non-coding RNAs (lncRNAs) HOXA transcript at the distal Tip (HOTTIP) may influence oral cancer cell growth an...
Oral cancer is the sixth leading cause of cancer-related mortality worldwide. Recent studies suggest that long non-coding RNAs (lncRNAs) HOXA transcript at the distal Tip (HOTTIP) may influence oral cancer cell growth and invasion, but comprehensive genetic association studies evaluating the impact of single-nucleotide polymorphisms (SNPs) on oral cancer susceptibility, and clinicopathological features are lacking. In this study, we investigated the associations between SNPs in the gene and both oral cancer susceptibility and clinicopathological characteristics. A total of 1,192 controls and 1,205 oral cancer patients were genotyped for four SNPs-rs3807598, rs17501292, rs2067087, and rs1859168-using real-time polymerase chain reaction (PCR). Our results showed that among oral cancer patients aged 60 years or older, those carrying the rs3807598 "GC+CC" genotype had a significantly reduced risk of developing advanced clinical stage and lymph node metastasis. Additionally, carriers of the rs2067087 "CG+GG" polymorphic variants were associated with a lower risk of developing advanced clinical stages. In conclusion, our findings suggest that the rs3807598 and rs2067087 polymorphisms may serve as pivotal predictor for assessing oral cancer progression.
From Spatial Patterns to Prognosis: Decoding Single-Cell Architecture in Cancer with Hyperplex Immunofluorescence Imaging.
Azimi M
J Cancer · 2025 · PMID 40959106 · Full text
Cancer prognosis relies not only on genetic and molecular biomarkers but also on the spatial organization of tumor and immune cells within the tumor microenvironment. Recent advances in spatial biology, particularly hype...
Cancer prognosis relies not only on genetic and molecular biomarkers but also on the spatial organization of tumor and immune cells within the tumor microenvironment. Recent advances in spatial biology, particularly hyperplex immunofluorescence (IMF) imaging, have enabled high-dimensional, quantitative assessment of cell-cell interactions at the protein level. Nearest neighbor analysis (NNA) and proximity analysis have emerged as crucial computational methods for quantifying spatial distributions of tumor, stromal, and immune cells in hyperplex IMF datasets, providing insights into tumor heterogeneity, immune infiltration, and treatment response. This review explores the current state of nearest neighbor and proximity analysis in cancer research, focusing on their applications in prognosis using single-cell spatial proteomics data generated by hyperplex IMF imaging. We summarize key computational approaches, including nearest neighbor distance metrics, Ripley's K-function, Voronoi tessellation, and graph-based models, that characterize spatial architecture within the tumor microenvironment. We highlight recent applications of hyperplex IMF in cancers showcasing how spatial proteomic signatures improve prognostic models. Furthermore, we discuss the integration of machine learning and AI-driven methods to leverage these spatial features for predictive modeling. Despite significant progress, challenges remain, including standardization of methodologies, variability in imaging technologies, and the need for large-scale, high-quality datasets. Addressing these challenges could lead to more accurate risk stratification and personalized treatment strategies. By providing a comprehensive overview of nearest neighbor and proximity analysis in the context of hyperplex IMF-based spatial proteomics, this review aims to bridge the gap between computational methodologies and clinical applications, offering new perspectives on how spatial organization at the protein level influences cancer prognosis.
Pan-Cancer Analysis of GPR141: Unveiling its prognostic significance, immune microenvironment interactions, and therapeutic potential.
Sun J, Qin S, Li Z … +4 more , Peng X, Xiao D, Tao Y, Xie B
J Cancer · 2025 · PMID 40959105 · Full text
GPCRs play an important role in the development of cancer. However, as a member of the G protein-coupled receptor family, the function of GPR141 is still unclear, and its function in pan-cancer is even less known. In th...
GPCRs play an important role in the development of cancer. However, as a member of the G protein-coupled receptor family, the function of GPR141 is still unclear, and its function in pan-cancer is even less known. In this study, a series of bioinformatics methods were used to explore the potential carcinogenic effects of GPR141, including analysis of GPR141 expression in different tumors, related prognosis, mutations, gene correlation analysis, gene enrichment analysis, immune cell infiltration and other factors. All results and data are available from TIMER, GEPIA2.0, TISIDB, cBioportal and other data portals. In addition, we collected lung adenocarcinoma samples, hepatocellular carcinoma and adjacent tissues for immunohistochemical analysis. And we stably knocked down GPR141 in lung adenocarcinoma cell lines A549 and H1975, and the changes of cell proliferation, migration and invasion were detected by CCK8, Transwell migration and invasion experiments. GPR141 is differentially expressed in a variety of cancers. GPR141 is closely related to the prognosis, genetic changes and immune infiltrating cells of tumor patients. Gene enrichment analysis showed that GPR141 was mainly involved in immune-related pathways in pan-cancer. In pan-cancer, the expression levels of PTPRC, TLRB, PLEK, NCKAP1L, PGS18 and CLEC12A were positively correlated with GPR141. Immunohistochemical results showed that the expression of GPR141 in lung adenocarcinoma and hepatocellular carcinoma was higher than that in adjacent tissues. After knocking down GPR141 in A549 and H1975, we found that the proliferation, migration and invasion of lung adenocarcinoma cells decreased after knocking down GPR141. GPR141 may be a new prognostic marker and therapeutic target for human tumors, providing a theoretical basis for the development of more effective and targeted clinical treatment of cancer.
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