J Cancer [JOURNAL]
Sun
200 papers
Capsaicin, the Pungent Component of Red Chili Pepper, induces p21-mediated Cell Cycle Arrest in Renal Cell Carcinoma via Downregulating GLI1: an Experimental Research .
Zheng L, He Y, Huang H … +1 more , Qu W
J Cancer · 2025 · PMID 41323789 · Full text
Capsaicin is the pungent and bioactive compounds of Previous studies have demonstrated the potent anti-tumor effect of capsaicin on various human malignancies by experiments or . However, the mechanism underlying its a...
Capsaicin is the pungent and bioactive compounds of Previous studies have demonstrated the potent anti-tumor effect of capsaicin on various human malignancies by experiments or . However, the mechanism underlying its antitumor efficiency is not fully elucidated. Cell cycle arrest is one of anti-proliferation mechanisms for anti-neoplastic drugs. The p21 protein, an important inhibitor of cell cycle progression, could block cyclin dependent kinases (CDKs) mediated activation of cyclins. As the downstream transcriptional factor of the Hh pathway, GLI1 plays a crucial role in cancer progression and prognosis evaluation. The aim of the present study is to explore the potential role of GLI1 in p21 mediated cell cycle arrest induced by capsaicin treatment in renal cell carcinoma (RCC) 786-O and Caki-1 cell lines. The results revealed that capsaicin could inhibit proliferation of RCC cells and cause G/G cell cycle arrest . Besides, we discovered that the capsaicin treatment increased the expression of p21 protein and downregulated the expression of GLI1, suggesting that GLI1 was involved in the p21 mediated G/G arrest induced by capsaicin administration in RCC 786-O and Caki-1 cell lines. In conclusion, our study demonstrated that capsaicin could induce p21 mediated cell cycle arrest via suppressing GLI1 to inhibit RCC cell proliferation, which might be a promising therapeutic strategy in RCC.
Divulging Patterns: An Analytical Review for Machine Learning Methodologies for Breast Cancer Detection.
Saleem A, Umair M, Naseem MT … +5 more , Zubair M, Obregon SA, Iglesias RC, Hassan S, Ashraf I
J Cancer · 2025 · PMID 41323788 · Full text
Breast cancer is a lethal carcinoma impacting a considerable number of women across the globe. While preventive measures are limited, early detection remains the most effective strategy. Accurate classification of breast...
Breast cancer is a lethal carcinoma impacting a considerable number of women across the globe. While preventive measures are limited, early detection remains the most effective strategy. Accurate classification of breast tumors into benign and malignant categories is important which may help physicians in diagnosing the disease faster. This survey investigates the emerging inclination and approaches in the area of machine learning (ML) for the diagnosis of breast cancer, pointing out the classification techniques based on both segmentation and feature selection. Certain datasets such as the Wisconsin Diagnostic Breast Cancer Dataset (WDBC), Wisconsin Breast Cancer Dataset Original (WBCD), Wisconsin Prognostic Breast Cancer Dataset (WPBC), BreakHis, and others are being evaluated in this study for the demonstration of their influence on the performance of the diagnostic tools and the accuracy of the models such as Support vector machine, Convolutional Neural Networks (CNNs) and ensemble approaches. The main shortcomings or research gaps such as prejudice of datasets, scarcity of generalizability, and interpretation challenges are highlighted. This research emphasizes the importance of the hybrid methodologies, cross-dataset validation, and the engineering of explainable AI to narrow these gaps and enhance the overall clinical acceptance of ML-based detection tools.
Isoginkgetin Induces Caspase Cascade Activation and Cell Apoptosis via JNK Signaling in Oral Cancer.
Yang WE, Chuang CY, Lin CW … +6 more , Su CW, Tsai MY, Su SC, Wu HH, Yang SF, Chen YT
J Cancer · 2025 · PMID 41323787 · Full text
Isoginkgetin (IGG), a naturally occurring biflavonoid found in the leaves of many medicinal plants, is known to inhibit pre-mRNA splicing and display anti-cancer characteristics. However, knowledge regarding the use of I...
Isoginkgetin (IGG), a naturally occurring biflavonoid found in the leaves of many medicinal plants, is known to inhibit pre-mRNA splicing and display anti-cancer characteristics. However, knowledge regarding the use of IGG on oral squamous cell carcinoma (OSCC) lags behind that on the other common malignancies. The aim of this study is to explore whether IGG hinders OSCC proliferation and further investigated its oncostatic actions. We demonstrated that exposure of OSCC cell lines (HSC-3 and SCC-9) to IGG significantly diminished cell viability and induced apoptotic cell death. Furthermore, levels of several tentative apoptosis suppressors (cIAP-1 and XIAP) were decreased in IGG-treated HSC-3 and SCC-9 cells, accompanied with increased cleavage of caspases. Of note, such activation of caspase cascades by IGG was reduced by pharmaceutical inhibition of c-Jun N-terminal kinase (JNK) via a specific kinase antagonist, suggesting a functional connection of JNK activity with caspase activation during IGG-induced oral cancer cell apoptosis. In conclusion, we exhibited that IGG hampered cell viability and stimulated apoptotic events in OSCC, driven by a JNK-dependent pathway of caspase activations. Our findings present new insights into applications of a natural biflavonoid compound in fighting oral carcinogenesis.
2023 FIGO Staging of Endometrial Cancer with Molecular Classification: Dawn and Challenges.
Zhao W, Xu Q, Feng P … +6 more , Hu D, Xu H, Zhang X, Lin W, Zhou F, Li Y
J Cancer · 2025 · PMID 41323786 · Full text
To assess the prognostic performance of the 2023 FIGO staging system for endometrial cancer, which incorporates molecular classification (FIGO 2023m), we analyzed survival outcomes and compared them with the 2009 FIGO sy...
To assess the prognostic performance of the 2023 FIGO staging system for endometrial cancer, which incorporates molecular classification (FIGO 2023m), we analyzed survival outcomes and compared them with the 2009 FIGO system (FIGO 2009). We retrospectively reviewed 720 patients with endometrial cancer treated between 2013 and 2021. Staging was performed according to FIGO 2009 and FIGO 2023m. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Factors associated with survival were identified through univariate and multivariate Cox proportional hazards analyses. Of the 720 patients, 27.4% (197/720) were reclassified under FIGO 2023m, and 182 were upstaged from stage I to stage II, primarily due to p53 abnormalities (54.9%). Patients with stage I disease according to FIGO 2023m had comparable survival rates (PFS: 95.3% vs. 92.8%; OS: 99.2% vs. 95.9% under FIGO 2009). Within stage II, OS in patients classified as FIGO 2023m IIC was slightly lower than in stage IIC but did not differ statistically (92.3% vs. 86.9%). Aggressive histology, positive peritoneal cytology, and deep myometrial invasion were associated with poorer outcomes. Patients harboring POLE mutations showed excellent prognosis (5-year OS, 100.0%), even at advanced stages. : Compared with FIGO 2009, the FIGO 2023m staging system offers improved prognostic value and better discriminative ability. Incorporating molecular subtyping is crucial even in advanced disease. However, omitting peritoneal cytology from prognostic assessment may risk undertreatment. Continued refinement in quantifying lympho-vascular space invasion (LVSI) and differentiating complex endometrial-myometrial junctions from genuine myometrial invasion remains a challenge.
Chemopreventive Targeting of Oncogenic Stemness: EGCG-Mediated Suppression of the HIF-1α-PPARγ-Cancer Stem Cells Transcriptional Signature in 3D Glioblastoma Spheroids.
Fallah A, Payet-Desruisseaux M, Zgheib A … +3 more , Danalache BA, Eliopoulos N, Annabi B
J Cancer · 2025 · PMID 41323785 · Full text
Preventing the emergence and persistence of cancer stemness represents a promising strategy to reduce tumor aggressiveness and therapeutic failure. Cancer stem cells (CSCs), which contribute significantly to therapy resi...
Preventing the emergence and persistence of cancer stemness represents a promising strategy to reduce tumor aggressiveness and therapeutic failure. Cancer stem cells (CSCs), which contribute significantly to therapy resistance, recurrence, and metastasis, are sustained in part by metabolic reprogramming that enhances survival and self-renewal under stress conditions. To model the hypoxic core of solid tumors, three-dimensional (3D) glioblastoma (GBM) spheroid cultures were generated using human U87, U118, U138, and U251 cell lines and compared to their respective two-dimensional (2D) monolayer cultures. Total RNA was extracted, and gene expression was analyzed via RT-qPCR and targeted gene arrays. Transient gene silencing was performed using specific siRNAs, while pharmacological intervention involved treatment with (-)-Epigallocatechin-3-gallate (EGCG), a bioactive phytochemical derived from green tea. Adipogenesis was evaluated using Oil Red O staining. Compared to conventional 2D cultures, 3D spheroids exhibited elevated expression of hypoxia-inducible factor-1 alpha (HIF-1α) and upregulation of peroxisome proliferator-activated receptor gamma (PPARγ), identified through adipogenesis array screening. Adipogenic activity persisted in the 3D spheroid model, and EGCG treatment effectively suppressed the upregulation of and transcripts. This led to a significant downregulation of adipogenic genes (, , , ) and CSC-associated markers (, , , ), accompanied by reduced spheroid growth. These findings underscore EGCG's chemopreventive potential in disrupting early HIF-1α-mediated molecular pathways that reinforce GBM stemness. By targeting hypoxia-driven metabolic reprogramming, EGCG offers a dietary-based approach to modulate the CSC niche and potentially delay or prevent GBM progression. Moreover, the use of 3D spheroid models highlights their relevance in preclinical chemoprevention research, bridging the gap between simplistic 2D cultures and the complex biology of solid tumors.
COL6A2 drives clear cell renal cell carcinoma progression via integrin-dependent modulation of Wnt/β-catenin signaling.
Ji X, Yun Y, Zhu Z … +4 more , Wu T, Ruan M, Fan Y, Zhang Q
J Cancer · 2025 · PMID 41323784 · Full text
The mechanistic role of COL6A2, an extracellular matrix protein, in clear cell renal cell carcinoma (ccRCC) is largely unexplored. This study aimed to investigate COL6A2 expression, its prognostic value, biological funct...
The mechanistic role of COL6A2, an extracellular matrix protein, in clear cell renal cell carcinoma (ccRCC) is largely unexplored. This study aimed to investigate COL6A2 expression, its prognostic value, biological functions, and underlying molecular mechanisms in ccRCC. COL6A2 expression was analyzed in ccRCC tissues and cell lines using public datasets and Western blotting on clinical samples and cell lines. Prognostic associations were evaluated using TCGA-KIRC data via clinicopathological correlations, Kaplan-Meier survival, and Cox regression analyses. Functional effects of COL6A2 knockdown in ccRCC cells were assessed by CCK-8, wound healing, Transwell, and Western blot analysis of EMT-associated proteins. Mechanistic investigations involved bioinformatic analysis, co-immunoprecipitation, Western blotting for Wnt/β-catenin pathway proteins, integrin blockade, and rescue experiments with the Wnt/β-catenin activator. COL6A2 mRNA and protein were significantly upregulated in ccRCC tissues and cell lines. High COL6A2 expression correlated with aggressive clinicopathological features and independently predicted poorer prognosis. COL6A2 knockdown significantly inhibited ccRCC cell proliferation, migration, invasion, and reversed epithelial-mesenchymal transition (EMT). Mechanistically, COL6A2 was found to physically interact with integrin β1, thereby activating the Wnt/β-catenin signaling pathway to induce EMT. Rescue experiments confirmed the role of this signaling axis in mediating the malignant phenotypes. COL6A2 promotes ccRCC aggressiveness and modulates Wnt/β-catenin signaling in an integrin-dependent manner. These findings nominate the COL6A2-integrin interface as a potential therapeutic and biomarker axis in ccRCC.
The immunosuppressive role of CCR8 Tregs in gastric cancer.
Jinushi K, Hayashi Y, Morishita K … +5 more , Saito T, Kawashima A, Doki Y, Ueyama A, Wada H
J Cancer · 2025 · PMID 41323783 · Full text
Gastric cancer remains one of the most common causes of cancer death, with a notably high incidence in East Asian countries. Regulatory T cells (Tregs) suppress antitumor immunity in the tumor microenvironment, and recen...
Gastric cancer remains one of the most common causes of cancer death, with a notably high incidence in East Asian countries. Regulatory T cells (Tregs) suppress antitumor immunity in the tumor microenvironment, and recent studies have identified C-C motif chemokine receptor 8 (CCR8) as a selective marker for tumor-infiltrating activated Tregs. However, the role of CCR8⁺ Tregs in gastric cancer remains unclear. This study retrospectively analyzed 80 gastric cancer patients who underwent curative resection. Immunohistochemistry dual staining for CCR8/Foxp3 and granzyme B/CD8 was performed, followed by automated image analysis and spatial profiling. The correlation between CCR8⁺ Tregs and CD8⁺ T cells, as well as their prognostic significance, was evaluated. CCR8⁺ Treg density positively correlated with CD8⁺ T cell infiltration. However, a low CD8⁺ T cell/CCR8⁺ Treg ratio was significantly associated with worse recurrence-free survival (P = 0.023). Reduced granzyme B expression was observed in CCR8⁺ Treg-dense hotspots, suggesting the presence of a localized immunosuppressive environment. Spatial analysis revealed that CCR8⁺ Tregs were preferentially localized at the tumor invasion front. Furthermore, distance analysis showed that fewer CD8⁺ T cells were present around CCR8⁺ Tregs than around CCR8⁻ Tregs, suggesting a localized immunosuppressive effect that may restrict CD8⁺ T cell proliferation. Our findings suggest that CCR8⁺ Tregs suppress antitumor immunity in gastric cancer by affecting surrounding CD8⁺ T cells through spatial segregation. Targeting CCR8⁺ Tregs may offer a promising strategy to improve the efficacy of immunotherapy in gastric cancer.
Dasatinib inhibits PD-L1 expression via a proteasomal pathway in pancreatic ductal adenocarcinoma cells.
Ko CC, Li HY, Yang PM
J Cancer · 2025 · PMID 41323782 · Full text
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5-year survival rate of below 8%. Standard chemotherapy regimens, including gemcitabine and FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and...
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5-year survival rate of below 8%. Standard chemotherapy regimens, including gemcitabine and FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin), offer limited clinical benefits. Although immune checkpoint inhibitors (ICIs) have revolutionized cancer immunotherapy, PDAC remains largely unresponsive to ICI monotherapy. In this study, we demonstrate that dasatinib, a multi-targeted tyrosine kinase inhibitor, reduces programmed death ligand 1 (PD-L1) expression in PDAC cells via a proteasome-dependent degradation pathway. Moreover, PD-L1 levels were correlated with dasatinib sensitivity, suggesting its utility as a predictive biomarker. These findings not only elucidate a novel mechanism of dasatinib's action but also provide a strong rationale for combining dasatinib with ICIs to overcome immune resistance and enhance therapeutic efficacy against PDAC.
FoxM1 promotes TFAM expression and regulates Mitochondrial Dynamics in Glioblastoma cells.
Moazzam NF, Iqbal MA, Han X … +2 more , Li Z, Gong A
J Cancer · 2025 · PMID 41323781 · Full text
To investigate the contribution of individual arginines, we employed site-directed mutagenesis to generate arginine-to-alanine (R→A) substitution mutations in the N-terminal domain of Forkhead box M1 (FoxM1). The R15A mu...
To investigate the contribution of individual arginines, we employed site-directed mutagenesis to generate arginine-to-alanine (R→A) substitution mutations in the N-terminal domain of Forkhead box M1 (FoxM1). The R15A mutation impaired FoxM1 transcriptional activity, hindered FoxM1 nuclear translocation and failed to promote the migratory and invasive behavior of glioma cells than other single arginine mutations. Furthermore, we demonstrated that FoxM1 expression was associated with Mitochondrial transcription factor A (TFAM) expression. Overexpressing FoxM1 increased TFAM protein levels, which was reversed by FoxM1 knockdown in glioblastoma multiforme (GBM) cells. The siRNA-mediated reduction of TFAM expression was rescued by FoxM1 overexpression. Also, FoxM1 overexpression promoted TFAM promoter luciferase activity. Importantly, the R15A mutation failed to promote TFAM expression. Additionally, FoxM1 increased the expression of mitochondrial fusion markers, Optic atrophy protein 1 (OPA1) and Mitofusin 1 (MFN1) and led to interconnected mitochondria, while FoxM1 knockdown reversed this effect. Moreover, FoxM1 promoted mitochondrial fission markers, Dynamin-related protein 1 (DRP1), Mitochondrial fission factor (MFF) and Mitochondrial fission protein 1 (FIS1). Notably, the R15A mutation resulted in loss of FoxM1 regulation of fusion and fission-related protein expression. Taken together, our findings reveal that that the N-terminal arginine 15 is a key site for the transcriptional activation and function of FoxM1 in GBM cells, suggesting its potential as a therapeutic target in GBM.
Molecular Mechanisms and Novel Therapeutics Targeting Ferroptosis in Gastric Cancer: A Literature Review.
Hsieh HL, Yu MC, Tseng HC … +2 more , Wu YH, Tsai MM
J Cancer · 2025 · PMID 41323780 · Full text
Since the discovery of ferroptosis, which plays an important role in gastric cancer (GC), its activation has been crucial for developing tumor therapeutic strategies. Recently, ferroptosis activation has become a researc...
Since the discovery of ferroptosis, which plays an important role in gastric cancer (GC), its activation has been crucial for developing tumor therapeutic strategies. Recently, ferroptosis activation has become a research hotspot for GC treatment approaches. Energy and metabolism dysfunctions involving lipids, amino acids, iron, sugars, and nucleotides caused by GC cells in a typical hypoxic microenvironment are important disease characteristics. However, the immune escape mechanism of GC cells limits the occurrence of programed cell death, a controllable form of which is ferroptosis. First, excessive reactive oxygen species production induces changes in intracellular iron ion levels, resulting in an imbalance in the antioxidant defense system. Finally, excessive accumulation of intracellular lipid peroxidation byproducts destroys cell membrane consistency and causes cell death. The promotion of ferroptosis in GC cells has been widely employed as a method for inhibiting tumor growth and chemotherapy resistance, which is helpful for developing anti-GC targeted treatments. Because GC cells are sensitive to ferroptosis-inducing agents, some traditional antitumor drugs (e.g., cisplatin) and Chinese herbal or natural medicines (e.g., artemisinin) exert anticancer effects by inducing this process. In this article, we summarize the basic molecular mechanisms underlying ferroptosis and the involved tumor markers, along with associated chemotherapy drugs and natural medicines. To activate ferroptosis in GC, new targeted drug therapies can be used within the clinical treatment field to kill GC cells and enhance tumor sensitivity to chemotherapy.
The Prognostic Value of Lymph Node Downstaging Following Neoadjuvant Chemoimmunotherapy for Non-Small Cell Lung Cancer.
Guo M, Abdel-Rasoul M, Chang J … +5 more , Guo A, Baiu I, D'Souza DM, Merritt RE, Kneuertz PJ
J Cancer · 2025 · PMID 41323779 · Full text
: The use of immune checkpoint inhibitors (ICI) and other targeted molecular agents for non-small cell lung cancer (NSCLC) has led to unprecedented rates of major pathologic response and improvements in overall survival....
: The use of immune checkpoint inhibitors (ICI) and other targeted molecular agents for non-small cell lung cancer (NSCLC) has led to unprecedented rates of major pathologic response and improvements in overall survival. The aim of this study was to evaluate the prognostic significance of lymph node downstaging following neoadjuvant chemoimmunotherapy for resectable NSCLC. : This study used retrospective data from the National Cancer Database (NCDB), which was queried for all patients diagnosed with NSCLC between 2017-2021 who underwent lung cancer surgery after receiving neoadjuvant chemoimmunotherapy. Only those staged as cN1 or cN2 were included. Patients were stratified according to post-therapy pathologic lymph node status, whether positive (ypN+) or negative (ypN-). Five-year overall survival (OS) was examined using Kaplan-Meier analyses with log-rank tests. Univariate and multivariate Cox regression analyses were conducted to identify significant predictors of survival. : Of the total 621 patients, 229 (37%) were diagnosed with cN1 disease and 392 (63%) with cN2. With neoadjuvant chemoimmunotherapy, 59% of cN1 and 40% of cN2 patients were down-staged to ypN0. While 5-year OS was not significantly different according to clinical N stage (76% for cN1 vs. 63% for cN2, p=0.08), higher post-therapy nodal staging correlated with poorer long-term survival (5-year OS of 84% for ypN0, 64% for ypN1, and 51% for ypN2, p <0.001). On multivariate analysis, cN1 to ypN+ (HR 2.56, p=0.009) and cN2 to ypN+ (HR 3.09, p=0.001) were predictors of worse OS compared to cN1 to ypN-, while the difference was not statistically significant for cN2 to ypN- (HR 1.01, p=0.051). Among ypN- patients, similar 5-year OS was seen among those who received adjuvant chemoimmunotherapy and those who did not (82.2% vs. 86.2%, p = 0.26). : Patients receiving neoadjuvant chemoimmunotherapy for resectable NSCLC experience high rates of nodal down-staging. Achieving ypN0 status post-therapy strongly predicts favorable long-term survival in this population, while pretreatment cN stage becomes less prognostically relevant.
Genetic association of NEAT1 gene polymorphism with the progression of colorectal cancer.
Shiu BH, Hsieh YH, Huang CC … +4 more , Tang CH, Chang LC, Su SC, Yang SF
J Cancer · 2025 · PMID 41323778 · Full text
Colorectal cancer (CRC) is a globally common malignancy, whose complex disease etiology involves a genetic element. (), a long noncoding RNA (lncRNA) gene, has been demonstrated to play a key role in cancer development....
Colorectal cancer (CRC) is a globally common malignancy, whose complex disease etiology involves a genetic element. (), a long noncoding RNA (lncRNA) gene, has been demonstrated to play a key role in cancer development. To clarify the potential effect of gene polymorphisms on CRC susceptibility, three single-nucleotide polymorphisms (SNPs), including rs3825071, rs3741384, and rs512715, were assessed in 485 CRC patients and 485 sex- and age-matched non-cancer controls. We did not detect any significant association of these SNPs with the occurrence and clinicopathological features of CRC. Nevertheless, one SNP of gene, rs3825071, was found in association with the distant metastasis (CT+TT: CC, OR, 2.644; 95% CI, 1.328-5.263; p=0.005) among relatively younger patients (< 65 years old), indicating an age-specific effect of gene polymorphisms on the spread of CRC. Our stratification analysis revealed that the association of rs3825071 with CRC metastasis is anatomical site-specific, as cases of colon tumors but not of rectal tumors who bear at least one polymorphic allele of rs3825071 more commonly developed metastasis. Further exploration using the datasets from the Genotype-Tissue Expression (GTEx) Portal and The Cancer Genome Atlas (TCGA) showed that rs3825071 genotypes affected NEAT1 expression in the colon tissues, and elevated NEAT1 levels were associated with a worse survival rate in relatively younger patients (< 65 years old) with colon adenocarcinoma. These data suggest that altered expression levels of NEAT1 due to genetic polymorphisms may influence the progression of colon cancer.
Associations of serum lead with colorectal cancer: data from NHANES 1999-2020.
Zhong L, Peng Y, Luo L … +5 more , Huang L, Cheng F, Lu Y, Ju Y, Ouyang M
J Cancer · 2025 · PMID 41210696 · Full text
Exposure to lead, a harmful heavy metal, is one of the risk factors for the development of Colorectal cancer (CRC). However, limited information is available on the impact of serum lead on the incidence of CRC. Therefore...
Exposure to lead, a harmful heavy metal, is one of the risk factors for the development of Colorectal cancer (CRC). However, limited information is available on the impact of serum lead on the incidence of CRC. Therefore, this study utilized data from the National Health and Nutrition Examination Survey (NHANES) to explore the relationship between serum lead and CRC. A total of 32,894 American adults from the 1999-2020 NHANES cycles were included in this study, among whom 225 reported having CRC. Additionally, we also collected data on 3,024 other cancer patients from the same period. Weighted logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for the risk of CRC associated with serum lead, with adjustments for potential confounding factors. Restricted cubic spline (RCS) analysis was conducted to examine the dose-response relationship between serum lead and the risk of CRC. Concurrently, we performed propensity score matching (PSM) analysis and validated our conclusions through ICP-MS quantification in clinical tissue specimens. This study revealed that patients diagnosed with CRC exhibited significantly elevated serum lead levels in comparison to both the general population and other cancer cohorts. Weighted logistic regression analysis showed a significant positive correlation between serum lead and the risk of CRC with or without adjusting for sociodemographic variables, BMI, diabetes, hypertension, and other covariates. The RCS model detected a dose-response relationship. Subgroup analysis indicated that the association between serum lead and CRC was similar across different sociodemographic characteristics, health behaviors, and comorbidities. However, the risk of CRC increased with higher serum lead levels among individuals aged ≥45, males, whites, BMI ≥24, alcohol users, smokers, and patients with diabetes. Despite the lack of statistically significant differences in lead levels after PSM analysis-potentially attributable to cohort size variations-our ultimate ICP-MS quantification of clinical tissues revealed markedly elevated lead concentrations in CRC specimens ( <0.0001). This cross-sectional study indicates a significant positive correlation between serum lead and the risk of CRC. Further prospective studies are needed to confirm these findings and elucidate the underlying mechanisms.
CXCR4 Inhibition Induces Tumor Necrosis by Selectively Targeting the Proliferating Blood Vessels in Oral Squamous Cell Carcinoma.
Soe Y, Kawai H, Eain HS … +6 more , Yoshida S, Oo MW, Min ZZ, Takabatake K, Nakano K, Nagatsuka H
J Cancer · 2025 · PMID 41210695 · Full text
The C-X-C chemokine receptor type 4 (CXCR4) is a G protein-coupled transmembrane receptor that contributes to tumor growth and angiogenesis. While prior studies have primarily focused on CXCR4 expression in cancer cells...
The C-X-C chemokine receptor type 4 (CXCR4) is a G protein-coupled transmembrane receptor that contributes to tumor growth and angiogenesis. While prior studies have primarily focused on CXCR4 expression in cancer cells and its role in metastasis, a few have examined its involvement in tumor-associated vasculature. In this study, we reported for the first time that CXCR4 expression within the tumor vasculature is significantly associated with higher pathological grades of human oral squamous cell carcinoma (OSCC) (p<0.03). A previous study reported that inhibiting CXCR4 with AMD3100 induces tumor cell death and enhances the efficacy of the chemotherapeutic agent cisplatin. These findings suggest that CXCR4 is an important target for cancer treatment. However, the tumor vascular system is known to be heterogeneous within the tumor microenvironment (TME), which may influence the treatment outcomes. Therefore, this study aimed to explore the effect of CXCR4 antagonism on various blood vessels present within the oral squamous cell carcinoma (OSCC) tumor stroma. Although the efficiency of AMD3100 was not significant in MOC cancer cells, necrosis was induced in the TME when applied to a poorly differentiated OSCC model, highlighting the role of the TME. Notably, CXCR4 is found to be highly overlapped with CD105 angiogenic tumor vessels among various vascular markers. Treatment with AMD3100 leads to a marked reduction in the CD105 vessels and impairs the maturation of tumor micro-vessels, explaining the cause of observed necrosis. Thus, CXCR4 serves as a promising biomarker in OSCC, and its inhibition with AMD3100 offers the therapeutic potential, particularly in cases with advanced pathological grades.
Exploring the Glycolytic Mechanisms in "Driver Gene-Negative" Lung Adenocarcinoma (LUAD): A Single-Cell RNA Sequencing Approach to Identify the MIF-HIF-1α Axis.
Yang HS, Li YH, Chen Q … +6 more , Luo HH, Yu QD, Han Y, Zhu W, Zhang J, Liang CY
J Cancer · 2025 · PMID 41210694 · Full text
: Patients with "driver gene-negative" LUAD lack effective targeted therapies. This study aimed to elucidate the role of the glycolysis pathway in driver gene-negative LUAD to identify key genes and potential therapeutic...
: Patients with "driver gene-negative" LUAD lack effective targeted therapies. This study aimed to elucidate the role of the glycolysis pathway in driver gene-negative LUAD to identify key genes and potential therapeutic targets. : Bulk RNA sequencing data from 49 patients with driver gene-negative LUAD were analyzed. The driver gene-negative status of patients was confirmed by immunoblotting. Gene set enrichment analysis (GSEA) was conducted on six hallmark pathways related to glycolysis. Additionally, key genes were identified and a risk score model was constructed. Finally, single-cell RNA sequencing data were processed using the Seurat package for data cleaning, dimensionality reduction clustering, and cell type identification. : GSEA analysis revealed significant enrichment of the glycolysis pathway in driver gene-negative LUAD. Differential expression analysis identified 144 genes associated with the glycolysis pathway. Six glycolysis-related genes (ANKZF1, GPR87, KIF2A, LCT, MIF, SDHC) were identified associated with poor prognosis. Single-cell sequencing analysis validated the key role of MIF in the glycolysis process and revealed a positive feedback regulatory axis between MIF and HIF-1α, which may promoting glycolysis and malignant transformation. : This study elucidated glucose metabolic reprogramming mechanisms and highlighted the MIF-HIF-1α axis as a promising therapeutic target in "driver gene-negative" LUAD, which may offer new avenues for improving outcomes, particularly those lacking conventional targeted therapy options.
Expression of CX3CL1 in the neoplastic lung tissue of squamous cell lung cancer.
Salgado-Aguayo A, Rivas-Fuentes S, Vázquez-Manríquez ME … +4 more , Soto-Nava M, Luna-Rivero C, Sevilla-Reyes E, Ávila-Ríos S
J Cancer · 2025 · PMID 41210693 · Full text
Lung cancer has one of the highest mortality rates. Although epidermoid lung cancer is one of the most prevalent subtypes of lung cancer, no targeted therapy is currently available for this type of cancer. CX3CL1 is a ch...
Lung cancer has one of the highest mortality rates. Although epidermoid lung cancer is one of the most prevalent subtypes of lung cancer, no targeted therapy is currently available for this type of cancer. CX3CL1 is a chemokine that has emerged as a potential molecular target for several malignancies. Chemokines direct the migration of various cell types to the tumor and influence tumor cell behavior. To date, little information is available on the role of this chemokine in squamous cell lung cancer. Using immunofluorescence, we evaluated the expression of CX3CL1 in histological specimens of neoplastic lung tissue from squamous cell lung cancer patients. CX3CL1 was expressed in squamous neoplastic lung tissues at all grades of tumor differentiation. We found this chemokine in the cytoplasm and nucleus of non-transformed cells in the adjacent tissue, but it was infrequent in the nucleus of neoplastic cells, which could have biological relevance.
NCAPH as a potential prognostic signaling biomarker regulating low-grade glioma cell proliferation, migration, invasion, immune microenvironment, and drug sensitivity.
Dai L, Jiang S, Zhou P
J Cancer · 2025 · PMID 41210692 · Full text
NCAPH is mainly involved in the transformation of nuclear chromatin in the intercellular phase into a highly heliform nuclear chromosome, encoded by a gene on chromosome 2q11.2. Studies have found that NCAPH, as an oncog...
NCAPH is mainly involved in the transformation of nuclear chromatin in the intercellular phase into a highly heliform nuclear chromosome, encoded by a gene on chromosome 2q11.2. Studies have found that NCAPH, as an oncogene, plays important roles in the occurrence and development of several cancers, significantly affecting the survival and prognosis of patients. However, the role of NCAPH in low-grade glioma (LGG) has been largely unexplored. Here, we conduct a comprehensive analysis of NCAPH expression, abundance of cell subsets in single-cell cohorts, prognosis, co-localization, epigenetic alterations, functional enrichment, tumor immune-related features, immunotherapy response, drug sensitivity, and molecular docking in LGG. Our findings suggest that NCAPH is significantly overexpressed in LGG and is strongly relevant to poor prognosis, and that NCAPH plays important roles in reshaping the tumor microenvironment, which may promote immune tolerance of LGG and thus become a potential immunotherapeutic target. The sensitivity of LGG patients with high NCAPH expression to chemotherapy agents such as temozolomide also suggests the potential therapeutic effect of chemotherapy combined with immunotherapy. Furthermore, NCAPH was positively correlated with cell cycle, proliferation, DNA damage and repair, EMT, invasion, and apoptosis, while negatively associated with inflammation, quiescence and angiogenesis. Together, this study provides a comprehensive understanding of the role of NCAPH in LGG and suggests that NCAPH may be a potential prognostic biomarker for LGG patients, with potential for drug development and immunotherapy.
Tyrosine Kinase Inhibitors Outperform Immune Checkpoint Inhibitors in Bone-Predominant Metastatic Renal Cell Carcinoma: A Multicenter Real-World Analysis.
Meng L, Psutka SP, Gheeya J … +9 more , Li M, Noonavath M, Orcutt D, Gross E, Collier KA, Mortazavi A, Folefac E, Monk P, Yang Y
J Cancer · 2025 · PMID 41210691 · Full text
Bone-predominant metastatic renal cell carcinoma (mRCC) presents significant clinical challenges due to its associated morbidities and poor prognosis. Optimal first-line treatment remains unclear, largely because these p...
Bone-predominant metastatic renal cell carcinoma (mRCC) presents significant clinical challenges due to its associated morbidities and poor prognosis. Optimal first-line treatment remains unclear, largely because these patients are often excluded from clinical trials due to difficulties in measuring bone lesions. Emerging evidence suggests that bone metastases exhibit high angiogenesis gene signatures, potentially predicting favorable responses to tyrosine kinase inhibitors (TKIs). We conducted a multicenter retrospective analysis of patients with bone-predominant mRCC treated at The Ohio State University Comprehensive Cancer Center and Fred Hutchinson Cancer Center from January 2008 to June 2021. Bone predominance was defined as having a greater number of osseous metastases compared to extra-osseous sites using computed tomography or bone scans. Patients receiving first-line TKIs or immune checkpoint inhibitors (ICIs) were included; those treated with combination TKI-ICI therapies were excluded due to limited numbers. Demographic, clinical, and treatment data were collected. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methods and compared using the log-rank test. Univariate Cox regression analysis was conducted to identify factors associated with OS. A total of 69 patients with bone-predominant mRCC were identified, with 40 receiving TKIs and 29 receiving ICIs as first-line therapy. Baseline characteristics were comparable between groups. The median OS was significantly longer for patients treated with TKIs compared to those receiving ICIs (41.3 months vs. 19.3 months; log-rank = 0.036). A trend toward improved median PFS was observed in the TKI group (7.9 months vs. 4.9 months; = 0.075). Univariate analysis showed that treatment with ICIs was associated with an increased risk of death compared to TKIs (hazard ratio = 1.96; = 0.040). Objective response rates were higher in the TKI group (22.9% vs. 12.0%), although this difference was not statistically significant ( = 0.332). In this multicenter real-world analysis, first-line treatment with TKIs was associated with significantly improved OS compared to ICIs in patients with bone-predominant mRCC. These findings suggest that TKI-containing regimens may be the preferred front-line therapy for this patient subgroup. Prospective studies are warranted to validate these results and to optimize treatment strategies for bone-predominant mRCC.
Causal Relationship Between Metabolic Traits and Risk of NSCLC: A Two-Sample Mendelian Randomization Analysis.
Li X, Cui W, Duan C … +1 more , Zhang C
J Cancer · 2025 · PMID 41210690 · Full text
Although the impact of circulating metabolites on the immune microenvironment of lung cancer has been recognized, the causal relationship between these metabolites and non-small cell lung cancer (NSCLC) remains unclear....
Although the impact of circulating metabolites on the immune microenvironment of lung cancer has been recognized, the causal relationship between these metabolites and non-small cell lung cancer (NSCLC) remains unclear. We investigated whether 233 metabolic traits have a causal effect on NSCLC using data from population-based genome-wide association studies (GWAS). We employed the inverse variance weighted (IVW) method with random effects as the primary analytical tool. After performing two-sample Mendelian randomization (MR) analysis of 233 metabolic traits on NSCLC risk, we selected the significant ones for further sensitivity analyses. Applying a false discovery rate (FDR) correction (P < 0.05), we identified a causal relationship between two metabolic traits and NSCLC: the ratio of Omega-3 fatty acids to total fatty acids (Omega_3_pct) (OR: 1.18, 95% CI: 1.08-1.29, P=0.036) and the ratio of 22:6 docosahexaenoic acid to total fatty acids (DHA_pct) (OR: 1.26, 95% CI: 1.11-1.42, P=0.036). Sensitivity analyses yielded consistent results. We innovatively utilized GWAS data for multiple metabolic traits to conduct a two-sample Mendelian randomization analysis of the association between 233 metabolic traits and NSCLC. The findings suggest that higher proportions of Omega-3 fatty acids and 22:6 docosahexaenoic acid in total fatty acids may causally increase the risk of NSCLC, providing novel insights into the role of circulating metabolites in lung cancer development.
Local Genetic Correlations and Pleiotropy Reveal Shared Genetic Architecture Between COVID-19 Phenotypes and Prostate Cancer in European Populations.
Xiang R, Zhao X, Chen L … +3 more , Wu X, Xiao J, Jiang X
J Cancer · 2025 · PMID 41210689 · Full text
While a link between coronavirus disease 2019 (COVID-19) and prostate cancer (PrCa) has been observed in clinical settings, the shared underlying genetic influences remain unclear. Leveraging summary statistics from the...
While a link between coronavirus disease 2019 (COVID-19) and prostate cancer (PrCa) has been observed in clinical settings, the shared underlying genetic influences remain unclear. Leveraging summary statistics from the hitherto largest genome-wide association studies (GWASs) of European-ancestry populations, we performed the first comprehensive genome-wide cross-trait analysis to investigate the shared genetic architecture, pleiotropy, and potential causal relationships between three COVID-19 phenotypes and PrCa. We found no evidence of significant genome-wide genetic correlations between COVID-19 phenotypes and PrCa ( > 0.05). However, after partitioning the whole genome into 2353 independent regions, we observed significant local genetic correlations at chromosome 1 (chr1), chr7, and chr14 for PrCa with at least one COVID-19 phenotype ( < 0.05/2353). Cross-trait meta-analysis identified 22 independent single nucleotide polymorphisms (SNPs) shared between PrCa and at least one COVID-19 phenotype, totalling 25 associations, including 2 with infection, 14 with hospitalization, and 9 with critical illness. Transcriptome-wide association study (TWAS) revealed eight distinct shared genes (, , , , , , , and ), predominantly enriched in tissues of the respiratory, neurological, and reproductive systems. Bidirectional Mendelian randomization (MR) demonstrated no causal association between COVID-19 phenotypes and PrCa. Using a multi-layered analytical framework, our study provides novel insights into the shared genetic bases between COVID-19 phenotypes and PrCa, supported by significant local genetic correlations, pleiotropic SNPs, and shared genes. These findings highlight common biological mechanisms rather than direct causal relationships, suggesting the limited benefits of additional PrCa screening in COVID-19 survivors. Furthermore, the identified genes represent promising targets for future mechanistic research and clinical interventions, warranting further validation.
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