J Cancer [JOURNAL]
Sun
200 papers
Vemurafenib Induces Apoptosis via JNK Activation and AKT Inhibition in Hepatocellular Carcinoma.
Cho YR, Huang K, Liu Z … +10 more , Kim H, Kim CY, Ma L, Yee N, Kim CR, Park GH, Zhang J, Ryoo ZY, Kim SH, Kim MO
J Cancer · 2026 · PMID 42179788 · Full text
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and remains one of the leading contributors to cancer-related mortality worldwide, primarily due to the disease's therapeutic res...
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and remains one of the leading contributors to cancer-related mortality worldwide, primarily due to the disease's therapeutic resistance and marked tumor heterogeneity. Among the molecular mechanisms implicated in HCC progression, the dysregulation of the JNK and PI3K/AKT signaling pathways plays a critical role in tumor initiation, cell proliferation, and cell survival. Vemurafenib, a clinically approved inhibitor of mutant BRAF kinase, has shown robust antitumor activity across multiple malignancies. However, its therapeutic utility in HCC remains largely unexplored. METHODS: We investigated the anticancer effects of vemurafenib in two human HCC cell lines. RESULTS: Vemurafenib treatments led to significant declines in cell viability and colony formation, accompanied by marked reductions in the migratory and invasive behaviors of HCC cells. Mechanistically, vemurafenib enhanced JNK pathway activation while suppressing AKT phosphorylation. CONCLUSION: Vemurafenib markedly inhibited HCC cell proliferation and metastasis, which was accompanied by a pronounced induction of apoptosis and G0/G1 phase cell-cycle arrest. At the signaling level, these cellular responses were linked to enhanced JNK activation and the suppression of AKT phosphorylation, suggesting that vemurafenib may serve as a potential therapeutic agent for HCC.
MRI-Based Habitat Radiomics for Differentiating Early-Stage Endometrial Carcinoma from Submucous Leiomyoma: A Multicenter Validation Study.
Tian H, Yan A, Cao L … +5 more , Pan Z, Guo Y, Shen B, Wang J, Jiang J
J Cancer · 2026 · PMID 42179787 · Full text
OBJECTIVE: This study aimed to investigate the utility of magnetic resonance imaging (MRI)-based habitat radiomics for preoperatively distinguishing early-stage endometrial carcinoma (EC) from submucous leiomyoma (SML)....
OBJECTIVE: This study aimed to investigate the utility of magnetic resonance imaging (MRI)-based habitat radiomics for preoperatively distinguishing early-stage endometrial carcinoma (EC) from submucous leiomyoma (SML). MATERIALS AND METHODS: A retrospective study was conducted on uterine lesions patients who underwent MRI from three hospitals. The k-means clustering algorithm was applied to segment the MRI into distinct habitats based on T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and apparent diffusion coefficient (ADC) maps. Radiomic features were extracted from whole-tumor and these habitats and selected by the Pearson correlation coefficient and least absolute shrinkage and selection operator (LASSO) regression. A logistic regression (LR) model was constructed by these radiomics in the training set. RESULTS: A total of 231 eligible patients were incorporated, 97 EC and 134 SML confirmed by histopathology. In the training cohort, the AUCs of the models based on features from the whole-tumor, habitat_1, habitat_2, and habitat_3 were 0.826, 0.787, 0.770, and 0.907, respectively, while in the test and external validation cohorts, the corresponding AUCs were 0.774/0.751, 0.486/0.608, 0.663/0.514, and 0.858/0.881. Compared with whole-tumor model, habitat_3 model demonstrated incrementally improved predictive performance in the external validation cohort (0.881 [95% CI: 0.799-0.934]). CONCLUSION: MRI-based habitat radiomics offers incremental improvement for preoperative differentiation between early-stage EC and SML.
Multi-omics Data Reveal SLC9A3R2 Promotes Breast Cancer Progression and an Immunosuppressive Microenvironment.
Chen Z, Wang Y, Wang G … +3 more , Yu Y, Wang X, Cao X
J Cancer · 2026 · PMID 42179786 · Full text
The molecular mechanisms driving the occurrence and progression of breast cancer remain unclear, necessitating the identification of novel molecular biomarkers and therapeutic targets. This study aims to investigate the...
The molecular mechanisms driving the occurrence and progression of breast cancer remain unclear, necessitating the identification of novel molecular biomarkers and therapeutic targets. This study aims to investigate the role of () in breast cancer progression via an integrated multi-scale approach. Analysis of The Cancer Genome Atlas (TCGA) data revealed that is upregulated at both protein and mRNA level in breast cancer tissues, related to advanced tumor stage and poor prognosis, especially in luminal subtypes. Functional enrichment analyses linked high expression to epithelial-mesenchymal transition (EMT), estrogen response, and PI3K-AKT/MAPK signaling pathways. Additionally, expression was negatively correlated with the infiltration level of CD8+ T cell as well as the expression of four main immune checkpoint molecules. Single-cell RNA sequencing analysis of patient samples revealed that -positive tumor epithelial cells mediate aberrant cellular communication with endothelial cells, fibroblasts, and macrophages via specific ligand-receptor pairs involving , and . Cell functional assays showed that knockdown of significantly impaired the proliferation, migration, and invasion capacities of breast cancer cells. Our findings establish as a key promoter of breast cancer progression, influencing both intrinsic oncogenic pathways and the extrinsic tumor microenvironment (TME), which provides a novel insight for breast cancer treatment.
Integrative Machine Learning Framework Revealing TRPM4-Associated Signatures and Identifying SPATA6 as a Potential Biomarker in Prostate Cancer.
Zhou H, Mei W, Wang J … +1 more , Liu X
J Cancer · 2026 · PMID 42179785 · Full text
BACKGROUND: The non-selective cation channel TRPM4 can induce necrotic cell death through sodium overload, yet its role in prostate cancer (PCa) progression remains poorly characterized. MATERIALS AND METHODS: Using TCGA...
BACKGROUND: The non-selective cation channel TRPM4 can induce necrotic cell death through sodium overload, yet its role in prostate cancer (PCa) progression remains poorly characterized. MATERIALS AND METHODS: Using TCGA-PCa transcriptomic data centered on TRPM4, we identified transcriptional signatures linked to sodium overload. Leveraging prognostic features, we developed robust prognostic models via ten machine learning algorithms and their combinations, training on TCGA data and validating on internal validation set, GSE46602 and GSE116918. We assessed the model's associations with clinicopathological features, prognosis, immune infiltration, and drug response. Expression of the 10 key model genes was validated in PCa cell lines versus a normal prostate epithelial cell. For SPATA6-the top-contributing gene-we overexpressed it in PCa cells to assess its functional impact. RESULTS: We identified 91 overlapping genes from TRPM4-associated and PCa-related differentially expressed genes. Functional enrichment implicated these genes in small GTPase activity, Rap1 signaling, and cAMP signaling. A TRPM4-related signature model (TRSM) comprising 10 key genes demonstrated strong prognostic performance across training and validation cohorts. TRSM-based risk stratification revealed significant differences in disease-free survival, clinicopathological features, immune infiltration, and immunotherapy response. Drug sensitivity analysis indicated heightened docetaxel sensitivity in the high-risk group. assays confirmed downregulation of all 10 key genes in PCa. SPATA6 overexpression suppressed PCa cell proliferation and migration. CONCLUSION: Our findings underscore the importance of TRPM4-associated molecular features in PCa prognosis. TRSM shows potential as a predictive tool for patient outcomes and a guide for personalized therapy.
Deficiency Inhibits Lung Tumorigenesis Via Activating ER Stress.
Dai W, Xu D, Lei Y … +5 more , Zhang S, Yu T, Tao W, Chen X, Du X
J Cancer · 2026 · PMID 42179784 · Full text
Lung cancer remains the leading cause of cancer-related mortality worldwide, yet its molecular pathogenesis is not fully understood. Here, we identify encoding a mitochondrial β-ketothiolase as a novel oncogene in lung...
Lung cancer remains the leading cause of cancer-related mortality worldwide, yet its molecular pathogenesis is not fully understood. Here, we identify encoding a mitochondrial β-ketothiolase as a novel oncogene in lung cancer. Using a mouse model, we demonstrate that deficiency in mice significantly suppresses -driven lung tumor progression by impairing cancer cell proliferation and enhancing apoptosis. Mechanistically, loss induces proteotoxic endoplasmic reticulum (ER) stress, as evidenced by increased ATF6(N) and phosphorylation of eIF2α and subsequent upregulation of the pro-apoptotic factor CHOP. Crucially, knockdown of partially restores oncogenic potential in mice and rescues the growth defect of -depleted cells, establishing CHOP as a key downstream mediator. Consistent with its oncogenic role, HADHB protein is upregulated in 52% (19/36) of human lung tumors compared to adjacent normal tissues, and low mRNA levels are correlated with good prognosis in lung cancer patients. Our findings unveil a previously unrecognized - regulatory axis in lung cancer progression and provide preclinical rationale for targeting mitochondrial metabolism in combination with ER stress modulators as a therapeutic strategy.
Exploratory Serum Metabolomics Identifies Metabolic Subgroups Across the Gastric Dysplasia-Early Cancer Spectrum.
Chae S, You HS, Kim JG … +1 more , Cho JY
J Cancer · 2026 · PMID 42179783 · Full text
BACKGROUND: Gastric carcinogenesis involves progressive molecular and metabolic alterations, yet non-invasive biomarkers for early detection and risk stratification remain limited. This study aimed to characterize system...
BACKGROUND: Gastric carcinogenesis involves progressive molecular and metabolic alterations, yet non-invasive biomarkers for early detection and risk stratification remain limited. This study aimed to characterize systemic metabolomic changes across the gastric carcinogenesis spectrum and to investigate potential associations between serum metabolites and gastric microbiome-related pathways. METHODS: In this exploratory study, untargeted serum metabolomics was performed on samples from patients with gastric dysplasia or early gastric cancer (n = 40) and healthy controls (n = 14). Differential metabolite analysis, principal component analysis, and k-means clustering were used to identify metabolic alterations and potential metabolic subgroups. Microbial pathway associations were examined using metabolite origin inference based on gastric-resident taxa reported in prior studies. RESULTS: Eighteen metabolites were significantly altered in gastric carcinogenesis compared with healthy controls. Six metabolites displayed distinct profiles that suggest two metabolic subgroups, including one subgroup showing a metabolic pattern closer to that of healthy controls, independent of histologic severity. Microbial pathway inference suggested contributions from Pseudomonadota, Actinomycetota, and Bacillota, with ornithine-related metabolites emerging as a key metabolic link previously implicated in dysplasia-to-carcinoma progression. These findings highlight inter-patient heterogeneity and potential metabolic-microbial interactions underlying gastric carcinogenesis. CONCLUSION: These findings suggest that serum metabolomic profiling may capture metabolic heterogeneity across the gastric dysplasia-early gastric cancer spectrum and generate hypotheses regarding microbiome-related metabolic alterations. While exploratory in nature, this study provides preliminary evidence supporting the potential of serum metabolites as non-invasive indicators of early gastric carcinogenesis, warranting validation in larger and longitudinal cohorts.
The Overexpression of Myelin and Lymphocyte Protein (MAL) Downregulates MUC1 and Enhances Cisplatin Sensitivity in Non-Small Cell Lung Cancer Cells.
Saldaña-Villa AK, Vázquez-Almazán B, Flores-Maldonado C … +8 more , Vizuet-de-Rueda JC, Oropeza-Durán EN, Bonilla-Delgado J, Cortés-Malagón EM, Contreras RG, Teran LM, Ortiz-Quintero B, Lara-Lemus R
J Cancer · 2026 · PMID 42038033 · Full text
The epigenetic repression of myelin and lymphocyte protein gene () and over-expression of MUC1 protein are two well-documented hallmarks of various carcinomas including lung cancer. The purpose of this work was to invest...
The epigenetic repression of myelin and lymphocyte protein gene () and over-expression of MUC1 protein are two well-documented hallmarks of various carcinomas including lung cancer. The purpose of this work was to investigate whether ectopic expression of MAL could modify the proliferative activity of MUC1 in human lung adenocarcinoma HCC827 cells. We generated stable HCC827 cell lines, expressing GFP- or myc-MAL constructs, then, followed the expression of MUC1 by RT-qPCR and Western blot, and tested proliferation and sensitivity of those cells to cisplatin. Our results showed that ectopic expression of MAL nearly eliminated cellular levels of MUC1-C. This effect is primarily due to down-regulation of expression, as confirmed by RT-qPCR. Additionally, lysosomal-associated degradation of MUC1 may also contribute, as observed when the cells were treated with ammonium chloride and chloroquine. The reduced quantity of MUC1-C negatively affected both cyclin D1 and c-Myc, protein levels, which are linked to cell-proliferative signals involving MUC1-C. Furthermore, expression of MAL decreased the viability of HCC827 cells, and increased their sensitivity to cisplatin. MAL and MUC1 showed an antagonistic relationship in cancer cells, and these findings provide new insights with respect to the regulation of MUC1 and a better understanding of MAL as a potential tumor suppressor.
Prognostic Impact of UBA1 Expression in Breast Cancer.
Koch J, Vatter L, Heyer J … +5 more , Klar M, Juhasz-Böss I, Werner M, Kurowski K, Bronsert P
J Cancer · 2026 · PMID 42038032 · Full text
BACKGROUND: The use of established prognostic markers has improved the diagnostic stratification and therapeutic approaches of breast cancer. Ubiquitin-like modifier activating enzyme 1 (UBA1), a key enzyme in the ubiqui...
BACKGROUND: The use of established prognostic markers has improved the diagnostic stratification and therapeutic approaches of breast cancer. Ubiquitin-like modifier activating enzyme 1 (UBA1), a key enzyme in the ubiquitin-proteasome pathway, has been reported to play a role in the pathogenesis of various malignant tumors. However, its functional impact on breast cancer progression, especially across intrinsic subtypes, remains poorly understood. This study aimed to evaluate the prognostic relevance of UBA1 protein expression in patients with breast cancer. METHODS: Formalin-fixed, paraffin-embedded (FFPE) tissue samples from 413 chemotherapy-naïve patients with invasive breast cancer were obtained from the Institute of Surgical Pathology (ISP) at the University Medical Centre Freiburg in Germany. Haematoxylin and eosin (H&E)-stained slides were digitised and annotated to define regions of interest (ROIs) for tissue microarray (TMA) construction. TMA sections were immunohistochemically stained for UBA1 expression and intrinsic subtype markers, including oestrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67. All slides were digitised. UBA1 and intrinsic markers were evaluated and analysed using AI-assisted image analysis software (HALO AI). Furthermore, UBA1 expression was analysed separately in both tumor cells and tumor-associated stroma. All results were statistically correlated with clinicopathological data parameters. RESULTS: High UBA1 expression in both the tumor and stromal compartments was significantly associated with reduced overall survival (OS). Subtype-specific analyses revealed that elevated stromal UBA1 expression, particularly in the cytoplasm, was associated with poorer survival in luminal A and luminal B subtypes. Conversely, increased nuclear UBA1 expression in tumor cells was associated with worse outcomes in the luminal B subtype. Multivariable Cox regression analyses revealed that UBA1 expression in tumor cells was an independent prognostic marker. Furthermore, bivariate analyses revealed that high stromal UBA1 expression was associated with a broader range of adverse clinicopathological parameters, most notably at the cytoplasmic level. CONCLUSION: This study highlights the prognostic significance of UBA1 protein expression in breast cancer, thereby demonstrating its potential utility as a diagnostic and therapeutic target.
Deciphering Cancer Therapy-Induced Cardiotoxicity in the Era of Spatial and Multi-Omics from Systemic Mechanisms to Microenvironments.
Gou C, Li Q, Xiong T … +4 more , Lin S, Wang K, Liu J, Xue C
J Cancer · 2026 · PMID 42038031 · Full text
Cardio-oncology has emerged as a critical discipline addressing the cardiovascular sequelae of antineoplastic therapies. While traditional chemotherapy, targeted therapies, and immune checkpoint inhibitors (ICIs) have re...
Cardio-oncology has emerged as a critical discipline addressing the cardiovascular sequelae of antineoplastic therapies. While traditional chemotherapy, targeted therapies, and immune checkpoint inhibitors (ICIs) have revolutionized cancer survival, they are frequently accompanied by cardiotoxicity ranging from asymptomatic left ventricular dysfunction to fulminant myocarditis. Current clinical strategies, relying heavily on echocardiography and serum biomarkers, often fail to detect early molecular perturbations or elucidate the complex multicellular interactions within the cardiac microenvironment. The advent of multi-omics technologies, genomics, transcriptomics, proteomics, and metabolomics, has provided systemic insights into these pathomechanisms. More recently, the integration of single-cell RNA sequencing (scRNA-seq) and spatial omics has enabled "" visualization of cellular heterogeneity and intercellular communication, resolving the "blind spots" of bulk sequencing. This review synthesizes the current landscape of therapy-induced cardiotoxicity, highlights the limitations of conventional methodologies, and comprehensively examines how multi-dimensional omics strategies are reshaping our understanding of mechanisms, biomarker discovery, and precision cardioprotection.
A squamous epithelial gene interaction perturbation network index for risk stratification in esophageal squamous cell carcinoma.
Zhang C, Wang H, Wang H … +5 more , Wang X, Tang S, Li F, Wang LD, Sheng J
J Cancer · 2026 · PMID 42038030 · Full text
Esophageal squamous cell carcinoma (ESCC) exhibits substantial molecular heterogeneity and unfavorable clinical outcomes. Current transcriptomic advances are shifting the focus from static gene expression profiles to the...
Esophageal squamous cell carcinoma (ESCC) exhibits substantial molecular heterogeneity and unfavorable clinical outcomes. Current transcriptomic advances are shifting the focus from static gene expression profiles to the dynamic architecture of gene interaction networks. However, gene interaction perturbation signatures specific to ESCC remain poorly understood. This study aimed to develop a network-informed prognostic index derived from malignant epithelial cell signatures. In-house single-cell RNA sequencing data from 15 ESCC samples from the First Affiliated Hospital of Zhengzhou University were analyzed to identify dysregulated genes in malignant squamous epithelial cells. Then, a gene interaction perturbation network index (GIPNI) was constructed by systematically evaluating 75 combinations of machine-learning methods and validated across 3 independent cohorts. Associations between the GIPNI and genomic alterations, immune-related characteristics, and therapeutic response were also evaluated. Results showed ESCCs with high-GIPNI scores were associated with advanced clinicopathological features and overactivated mitotic cell cycle and epithelial cell differentiation pathways. Immune profiling suggested that low-GIPNI tumors had a more immune-infiltrated microenvironment. Notably, high-GIPNI ESCCs were associated with higher sensitivity to some common chemotherapeutic agents. Overall, the GIPNI provides a network-informed and malignant squamous cell-oriented framework for prognostic assessment in ESCC. This integrative approach may facilitate risk stratification and provide insights into individualized therapeutic strategies.
Longitudinal CT-based deep learning radiomics for predicting prognosis in esophageal squamous cell carcinoma treated with definitive chemoradiotherapy: a two-center study.
Hu X, Maitudi W, Chen X … +2 more , Zhao L, Pang Q
J Cancer · 2026 · PMID 42038029 · Full text
PURPOSE: To develop and validate a longitudinal deep-learning based survival prediction model for esophageal squamous cell carcinoma (ESCC) patients who received definitive concurrent chemoradiotherapy (CCRT). METHODS: A...
PURPOSE: To develop and validate a longitudinal deep-learning based survival prediction model for esophageal squamous cell carcinoma (ESCC) patients who received definitive concurrent chemoradiotherapy (CCRT). METHODS: A total of 257 ESCC patients from two centers were recruited. Among them, 205 patients were in the training cohort and 52 in the external testing cohort. The CrossFormer algorithm was utilized to extract features from pre- and post- treatment CECT scans. We constructed clinical, Delta-radiomics and deep-learning models. Models were evaluated by the C-index and integrated Brier score (iBS). Prognostic stratification was performed based on risk scores, and model interpretability was evaluated using Grad-CAM and SurvSHAP(t). RESULTS: The Fusion model demonstrated superior predictive performance, achieving a C-index of 0.768 (95% CI: 0.731-0.804) in the training cohort and 0.734 (95% CI:0.665-0.803) in the testing cohort. The Fusion model also showed the best calibration (Training cohort: iBS=0.096; Testing cohort: iBS=0.151). Patients were stratified into high-risk and low-risk groups based on risk scores, with significant differences in overall survival (OS) between the groups ( < 0.001). CONCLUSION: We developed a model integrating longitudinal CECT scans to predict OS in ESCC patients undergoing CCRT. The results highlight the importance of capturing tumor changes during treatment for accurate prognostic stratification. The model shows its potential for guiding personalized treatment strategies in clinical practice.
Targeting MUC16 to Reverse Anoikis Resistance: A Promising Strategy for Metastatic Lung Adenocarcinoma Therapy.
Kulsoom, Ali W, Ma Z … +3 more , Cai W, Wang Z, Wang F
J Cancer · 2026 · PMID 42038028 · Full text
BACKGROUND: Although the mucin glycoprotein is well established as an oncogenic biomarker in ovarian cancer, its mechanistic contribution to lung adenocarcinoma (LUAD) remains poorly defined. This study integrates multi...
BACKGROUND: Although the mucin glycoprotein is well established as an oncogenic biomarker in ovarian cancer, its mechanistic contribution to lung adenocarcinoma (LUAD) remains poorly defined. This study integrates multi-omics profiling and functional validation to uncover as a novel determinant of detachment-induced survival in LUAD. METHODS: Transcriptomic and clinical data from TCGA-LUAD and GEO cohorts were analyzed to identify differentially expressed anoikis-related genes. Functional enrichment, GSVA, and network analyses delineated key signaling pathways. Multi-omic integration including copy-number, methylation, immune infiltration, and pharmacogenomic data was used to explore upstream regulatory mechanisms. Experimental assays were performed in A549 cells following siRNA-mediated silencing, assessed by qRT-PCR, wound-healing, and transwell migration analyses. RESULTS: Nineteen overlapping anoikis-related differentially expressed genes (ARDEGs) were identified, with displaying the most significant upregulation in LUAD and a strong association with poor overall survival (HR = 1.04, p < 0.001). Pathway enrichment indicated activation of cell-adhesion, Hippo, and PI3K-AKT signaling networks. Multi-omic analysis revealed that promoter hypomethylation and copy-number gain drive overexpression, which correlates with reduced cytotoxic T-cell infiltration and an immunosuppressive microenvironment. Functionally, knockdown diminished cell adhesion, migration, and wound closure, consistent with loss of detachment survival capacity. CONCLUSION: This work establishes as a mechanistic mediator of metastatic competence in LUAD, acting through adhesion-linked PI3K-AKT signaling to protect tumor cells from detachment-induced apoptosis. Therapeutic inhibition of MUC16 may restore apoptotic susceptibility and suppress metastatic spread in lung cancer.
Orientin and Cancer Suppression: Molecular Mechanisms and Synergistic Effects.
Ahmed EA, Rajendran P
J Cancer · 2026 · PMID 42038027 · Full text
Orientin, a C-glycosyl flavonoid (luteolin-8-C-glucoside) naturally present in plants such as (holy basil), , rooibos tea, and species, exhibits a wide range of pharmacological activities, including antioxidant, anti-i...
Orientin, a C-glycosyl flavonoid (luteolin-8-C-glucoside) naturally present in plants such as (holy basil), , rooibos tea, and species, exhibits a wide range of pharmacological activities, including antioxidant, anti-inflammatory, and anticancer effects. In cancer research, orientin has been identified as a potent natural compound that can regulate several fundamental hallmarks of tumor progression, including excessive cell proliferation, resistance to apoptosis, angiogenic signaling, and metastatic dissemination. This review highlights orientin as a low-toxicity, naturally derived flavonoid that is generally well tolerated by healthy cells and may offer cytoprotective and antioxidant benefits, in contrast to conventional chemotherapeutics that often damage normal tissue, while selectively targeting cancer cells. The underlying molecular mechanisms responsible for orientin's inhibition of cancer progression, as well as its potential synergy with other therapies, are summarized. Collectively, these properties suggest a favorable pharmacological profile, supporting its consideration for clinical applications, especially in combination treatment approaches.
An integrated bulk and single-cell transcriptomic analysis reveals stemness-driven immune regulation and therapeutic vulnerability in colorectal cancer.
Chen IH, Chang KF, Chao CC … +14 more , Lin CH, Chang CH, Ko CC, Lin HR, Wu CJ, Yuan CH, Kumar S, Solomon DD, Xuan DTM, Palekkode N, Fathima A, Lee YK, Hsieh CB, Wu YJ
J Cancer · 2026 · PMID 42038026 · Full text
Tumor stemness is increasingly recognized as a key contributor to tumor heterogeneity, immune regulation, and therapeutic resistance in colorectal cancer (CRC). In this study, we developed a stemness-based risk model usi...
Tumor stemness is increasingly recognized as a key contributor to tumor heterogeneity, immune regulation, and therapeutic resistance in colorectal cancer (CRC). In this study, we developed a stemness-based risk model using bulk transcriptomic data from The Cancer Genome Atlas and evaluated its prognostic and therapeutic relevance through integrative analyses. The proposed risk score robustly stratified patients into distinct prognostic groups and remained an independent predictor of overall survival after adjustment for clinicopathological variables. Stemness-high tumors exhibited altered immune infiltration patterns and coordinated upregulation of immune checkpoint-related genes. Although the association between stemness score and immune evasion potential was modest, its clinical relevance was supported by validation in independent immunotherapy-treated cohorts, where low-risk patients demonstrated improved survival and higher response rates. Single-cell RNA sequencing (scRNA-seq) analysis further revealed that enhanced stemness and dedifferentiation were predominantly localized within malignant epithelial cells. Together, these findings establish tumor stemness as a central determinant of prognosis, immune regulation, and therapeutic vulnerability in CRC.
WISP-3 promotes angiogenesis in non-small cell lung cancer through p38/JNK-c-Jun-mediated PDGF-A upregulation.
Chang EM, Lin SL, Cheng CY … +4 more , Tang CH, Chen YC, Lee CW, Lin CY
J Cancer · 2026 · PMID 42038025 · Full text
Angiogenesis is a pivotal process for tumor progression and metastasis in non-small cell lung cancer (NSCLC). However, the molecular mechanisms by which WNT1-inducible signaling pathway protein 3 (WISP-3) contributes to...
Angiogenesis is a pivotal process for tumor progression and metastasis in non-small cell lung cancer (NSCLC). However, the molecular mechanisms by which WNT1-inducible signaling pathway protein 3 (WISP-3) contributes to NSCLC angiogenesis remain poorly defined. This study investigated the role of WISP-3 in regulating pro-angiogenic signaling in lung adenocarcinoma (LUAD) cells. Conditioned medium from H1299 and A549 cells treated with recombinant WISP-3 (0-100 ng/mL) significantly and dose-dependently enhanced the tube formation of human umbilical vein endothelial cells (HUVECs). WISP-3 selectively upregulated platelet-derived growth factor A (PDGF-A) expression at both mRNA and protein levels in NSCLC cell lines, while other angiogenic factors remained unaffected. Notably, knockdown of PDGF-A using siRNA markedly abolished WISP-3-induced HUVEC tube formation, confirming PDGF-A as a critical mediator in this process. Mechanistically, WISP-3 rapidly triggered the phosphorylation of p38 and JNK signaling pathways. These activations led to the phosphorylation of the transcription factor c-Jun, which in turn promoted PDGF-A gene expression. Pharmacological inhibition of p38 (Adezmapimod), JNK (SP600125), or c-Jun (T-5224) effectively suppressed WISP-3-induced c-Jun activation, PDGF-A expression, and subsequent angiogenesis. Collectively, our findings identify a novel WISP-3/p38-JNK/c-Jun/PDGF-A signaling axis that drives vascular remodeling in NSCLC. Targeting WISP-3 or its downstream effectors may represent a promising therapeutic strategy for anti-angiogenic treatment in lung cancer.
The Role of Lipid Metabolism in the Progression of Breast Cancer.
Liu TT, Wang MM
J Cancer · 2026 · PMID 42038024 · Full text
Breast cancer is one of the most prevalent malignancies globally, it is closely associated with lipid metabolism reprogramming. Targeting lipid metabolism pathways has become a promising strategy for breast cancer treatm...
Breast cancer is one of the most prevalent malignancies globally, it is closely associated with lipid metabolism reprogramming. Targeting lipid metabolism pathways has become a promising strategy for breast cancer treatment. Lipid metabolism encompasses the biochemical processes of lipid biosynthesis, catabolism, uptake, and post-synthetic modification. Dysregulation of these processes can promote tumorigenesis and cancer cell metastasis. This review summarizes four major facets of lipid metabolism, including fatty acid (FA) metabolism, cholesterol metabolism, phospholipid (PL) metabolism, and sphingolipid metabolism. It also discusses the roles of key molecules in these pathways in breast cancer, including FA synthase (FASN), cluster of differentiation 36 (CD36), and acyl-CoA synthetase long-chain family member 4 (ACSL4). These molecules may improve therapeutic responses, overcome drug resistance, and reshape the tumor immune microenvironment by regulating FA synthesis and lipid uptake. Targeting lipid metabolic pathways may provide potential biomarkers for patient stratification and therapeutic guidance, and may also offer new opportunities for cancer treatment.
Roles of Cellular Neighborhoods in Lung Cancer.
Bai R, Sun W
J Cancer · 2026 · PMID 42038023 · Full text
The occurrence and development of lung cancer (LC) involve complex interactions between various cell types in the tumor microenvironment (TME). Understanding the spatial distribution and interaction mechanisms of these c...
The occurrence and development of lung cancer (LC) involve complex interactions between various cell types in the tumor microenvironment (TME). Understanding the spatial distribution and interaction mechanisms of these cells may be the key to overcoming LC. The advancements of single-cell and spatial transcriptome techniques have promoted our understanding of cellular neighborhoods (CNs) and their functions in the pathogenesis of LC. In this review, we focus on the impact of different etiologies on LC CNs and the current research status of CNs in LC. This review may provide new insights into the molecular mechanisms of LC pathogenesis, develop more refined classification principles for LC diagnosis, and offer new perspectives for LC treatment.
Association between Oxidative Balance Score and Colorectal Cancer: Insights from NHANES 1999-2018.
Chen D, Xie B, Fang H … +5 more , Chang H, Qiu W, Fang J, Wu Y, Peng XE
J Cancer · 2026 · PMID 42038022 · Full text
BACKGROUND: Previous studies have indicated an association between high antioxidant exposure and colorectal cancer (CRC) risk in elderly populations. However, the relationship between the oxidative balance score (OBS) an...
BACKGROUND: Previous studies have indicated an association between high antioxidant exposure and colorectal cancer (CRC) risk in elderly populations. However, the relationship between the oxidative balance score (OBS) and CRC risk in the general population remains unclear. OBJECTIVE: In this study, we used the OBS, which is based on dietary and lifestyle factors, to assess the oxidative stress (OS) status of individuals and to explore the association between OBS and CRC risk in American adults. METHODS: Overall, 44,482 participants from the National Health and Nutrition Examination Survey (NHANES 1999-2018) were included in the cross-sectional study, of whom 340 had CRC. OBS, which consists of 20 dietary and lifestyle factors, was the exposure variable. Weighted multivariate logistic regression, subgroup analysis, and restricted cubic spline curves were used to assess the association between OBS and CRC. Sensitivity analyses were conducted to evaluate the robustness of the results. RESULTS: Multiple logistic regression showed that the CRC risk decreased by 2.0% for each OBS unit added (= 0.98, 95%: 0.96-1.00, =0.019). Compared with the lowest OBS reference group (T1), OBS in the highest tertile of OBS (T3) was associated with a reduced CRC risk (= 0.58, 95%: 0.39-0.84). Similarly, individuals in the highest dietary OBS tertile (T3) had a reduced CRC risk (= 0.63, 95%: 0.44-0.91), whereas no significant association was observed in lifestyle OBS and CRC. CONCLUSION: Higher OBS and dietary OBS were associated with CRC. A healthy lifestyle and antioxidant-rich diet may be useful for preventing CRC.
Circulating Tumor Cells Detected Using EpAb3-5 as Prognostic Indicators in Head and Neck Squamous Cell Carcinoma.
Hsu PC, Lung CF, Kuo CY … +2 more , Wu HC, Hsu YC
J Cancer · 2026 · PMID 42038021 · Full text
BACKGROUND: EpAb3-5, an anti-EpCAM (epithelial cell adhesion molecule) neutralizing antibody, enhances circulating tumor cell (CTC) detection, but its clinical and prognostic relevance in head and neck squamous cell carc...
BACKGROUND: EpAb3-5, an anti-EpCAM (epithelial cell adhesion molecule) neutralizing antibody, enhances circulating tumor cell (CTC) detection, but its clinical and prognostic relevance in head and neck squamous cell carcinoma (HNSCC) remains unclear. METHODS: We retrospectively analyzed 66 HNSCC patients. CTCs were enumerated using EpAb3-5 and a commercial EpCAM-based platform (MACS), and tumor EpCAM expression detected using EpAb3-5 was assessed by immunohistochemistry. Associations with clinicopathologic features were evaluated, and survival outcomes were analyzed using Kaplan-Meier and Cox regression models, truncated at five years. RESULTS: EpAb3-5 detected significantly more CTCs than MACS (p < 0.001), indicating greater detection sensitivity. Tumor EpCAM expression detected by EpAb3-5 correlated with nodal status (p < 0.01) but not T classification or overall stage. Although EpAb3-5-detected EpCAM expression alone was not an independent predictor of overall survival (OS) or disease-free survival (DFS), its integration with tumor staging revealed a context-dependent prognostic association. Specifically, low EpCAM expression assessed using EpAb3-5 identified early-stage patients with better OS (p < 0.05), whereas no significant survival differences were observed in advanced-stage disease. CONCLUSIONS: EpAb3-5 enhances CTC detection compared with a conventional EpCAM-based method and provides complementary prognostic information when interpreted alongside tumor staging. These findings indicate that EpCAM immunoreactivity assessed using EpAb3-5 may assist in refining risk stratification in early-stage HNSCC; however, these observations should be considered exploratory and warrant further validation in larger prospective cohorts.
Therapeutic Targeting of Oxidative Phosphorylation in Microsatellite Instability-High Gastric Cancer.
Ang B, Bai Y, Deng X … +10 more , Wu Q, Wang Y, Xu S, Zhang W, Li Y, Chen D, Li R, Li S, Zhao Z, Zhang Y
J Cancer · 2026 · PMID 42038020 · Full text
BACKGROUND: Gastric cancer is the third leading cause of cancer-related mortality worldwide. According to The Cancer Genome Atlas (TCGA), it can be classified into four molecular subtypes, including microsatellite instab...
BACKGROUND: Gastric cancer is the third leading cause of cancer-related mortality worldwide. According to The Cancer Genome Atlas (TCGA), it can be classified into four molecular subtypes, including microsatellite instability (MSI) and genomically stable (GS) subtypes, which display distinct clinical and pathological features. However, differences in their tumor microenvironment, particularly metabolic reprogramming, remain poorly understood. METHODS: Single-cell RNA sequencing data from gastric cancer patients classified as GS or MSI were enrolled. Cell clusters were identified and annotated to compare cellular landscapes between subtypes. Differential gene expression and pathway analyses were performed among malignant epithelial cells. Key genes related to oxidative phosphorylation were identified using LASSO regression, and their expression was further validated in the TCGA dataset. Patient-derived xenograft models were used to compare tumor growth rates, ATP levels, and expression of oxidative phosphorylation -related genes. RESULTS: Single-cell transcriptomic analysis revealed eight major cell types in MSI tumors. Compared to the GS subtype, MSI samples showed significantly greater infiltration of T cells and a lower proportion of epithelial cells. Malignant cells from MSI samples exhibited increased activity of oxidative phosphorylation pathways. LASSO regression identified five oxidative phosphorylation-related genes that were consistently overexpressed in MSI tumors in both single-cell and TCGA datasets. In Patient-derived xenograft models, MSI tumors grew more rapidly and demonstrated higher ATP levels and elevated expression of the five oxidative phosphorylation-related genes compared to MSS tumors. CONCLUSION: Our study reveals enhanced oxidative phosphorylation metabolism in MSI gastric cancer at single-cell resolution and identifies five oxidative phosphorylation-related genes that may serve as potential therapeutic targets for this subtype.
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