World Journal of Oncology最新文献

{"title":"Transcription Factor MAX Regulates Liver Cancer Cell Growth, Migration, Invasion, and Epithelial-Mesenchymal Transition by Promoting SF3A3 Expression.","authors":"Gui Zhou, Mei Yu Dai, Xiang Chen, Li Ming Liu, Fa Quan Lin","doi":"10.14740/wjon2783","DOIUrl":"10.14740/wjon2783","url":null,"abstract":"<p><strong>Background: </strong>The regulatory relationship between transcription factor MAX and splicing factor SF3A3 in hepatocellular carcinoma (HCC) is unknown. We investigated whether MAX directly regulates SF3A3 and their functional role in HCC progression.</p><p><strong>Methods: </strong>MAX and SF3A3 expression were analyzed in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-HCC) dataset (UALCAN, GEPIA) and validated in 33 paired HCC and adjacent non-tumor tissues by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Expression and prognostic significance were assessed across cancer stages, grades, and nodal status. Functional roles were evaluated in Hep3B (high expression) and PLC/PRF/5 (low expression) cells using shRNA-mediated knockdown and overexpression, respectively. Cell proliferation (cell counting kit-8, colony formation), migration (wound healing, Transwell), invasion (Matrigel Transwell), and epithelial-mesenchymal transition (EMT) (Western blot for E-cadherin, N-cadherin, and vimentin) were assessed. Mechanistic studies included chromatin immunoprecipitation (ChIP)-quantitative polymerase chain reaction (qPCR), luciferase reporter assays with site-directed mutagenesis, and Myc inhibition. <i>In vivo</i> tumor growth was evaluated using a xenograft mouse model.</p><p><strong>Results: </strong>MAX and SF3A3 were overexpressed in HCC tissues compared to normal liver, and high expression was correlated with reduced patient survival, advanced cancer stage, higher tumor grade, and nodal metastasis. A significant positive correlation between MAX and SF3A3 expression was observed. Functional assays demonstrated that MAX or SF3A3 overexpression promoted HCC cell proliferation, migration, invasion, and EMT, while knockdown suppressed these phenotypes. MAX directly bound the SF3A3 promoter (P3 E-box) and activated its transcription in a Myc-dependent manner. Overexpression of MAX or SF3A3 promoted malignant phenotypes, while SF3A3 knockdown reversed MAX-driven oncogenic effects <i>in vitro</i> and reduced tumor growth <i>in vivo.</i></p><p><strong>Conclusion: </strong>This study establishes a novel MAX-SF3A3 regulatory axis in which MAX directly binds the SF3A3 promoter and activates its transcription in a Myc-dependent manner, driving HCC cell proliferation, migration, invasion, EMT, and tumor growth. Targeting the MAX-SF3A3 axis represents a potential therapeutic strategy for HCC.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":"17 4","pages":"556-571"},"PeriodicalIF":2.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Bioinformatics Analysis Identifies NCAPG2 as an Immune-Related Prognostic Biomarker in Breast Cancer.","authors":"Jia Li, Qian Wang, Hao Qiao","doi":"10.14740/wjon2768","DOIUrl":"10.14740/wjon2768","url":null,"abstract":"<p><strong>Background: </strong>Non-SMC condensin II complex subunit G2 (NCAPG2) is an important molecule in regulating chromosome segregation of mitosis and acts as an oncogene and biomarker in various tumors. This study aimed to explore the role of NCAPG2 in breast cancer (BC).</p><p><strong>Methods: </strong>The mRNA and protein expression of NCAPG2 was explored in the Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), Human Protein Atlas (HPA), and bc-GenExMiner databases. Survival analyses were performed using the Kaplan-Meier plotter and bc-GenExMiner databases. We used the COSMIC, CistromeDB, and cBioPortal databases to analyze the transcriptional regulation and genetic alteration. Function enrichment analyses were performed with CancerSEA and Metascape database.</p><p><strong>Results: </strong>NCAPG2 expression was significantly higher in BC than normal samples. NCAPG2 expression was positively correlated with the Scarff-Bloom-Richardson (SBR) grade, HER2 status, lymph nodal status, TP53 and BRCA1/2 mutation, and Nottingham prognostic index (NPI), while negatively correlated with age, ER status, and PR status. Survival analyses indicated that overexpressed NCAPG2 was associated with the adverse prognosis of BC. Gene Set Enrichment Analysis (GSEA) and function enrichment analyses of single-cell and co-expressed genes of NCAPG2 consistently showed that NCAPG2 was involved in cell cycle, immune, DNA damage, cancer-related pathways, proliferation, and DNA repair. The result of TIMER showed that NCAPG2 was associated with infiltrating immune cells and the exhausted T cell phenotype, such as CD8⁺ T cells, PD-1, CTLA4, and TIM-3.</p><p><strong>Conclusion: </strong>We found that the mRNA and protein expression of NCAPG2 was upregulated in BC. Overexpressed NCAPG2 might act as an adverse prognosis biomarker in BRCA and had a distinct function in the cell cycle, proliferation, and immune infiltration.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":"17 4","pages":"509-523"},"PeriodicalIF":2.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Potential Nuclear Factor-Kappa B1 Gene Polymorphism rs28362491 and miR-206 Level in Patients With Acute Lymphoblastic Leukemia.","authors":"Isra Muradi, Jehad Alhmoud, Moath Al-Qaraleh, Maher Sughayer, Khalid Halahleh","doi":"10.14740/wjon2762","DOIUrl":"10.14740/wjon2762","url":null,"abstract":"<p><strong>Background: </strong>microRNAs (miRNAs) and the nuclear factor-kappa B1 (NF-κB1) signaling pathway play a critical role in leukemogenesis. The miR-206 and NF-κB1-94 ATTG polymorphism (rs28362491) have a potential impact on cancer progression and treatment response. The primary objective of this study was to evaluate the levels of expression of miR-206, the genotypic distribution of the NF-κB1-94 ATTG polymorphism, and the secondary objective was to assess their relationship in patients with acute lymphoblastic leukemia (ALL), Hodgkin lymphoma (HL), and healthy controls.</p><p><strong>Methods: </strong>This was a retrospective case-control study conducted at King Hussein Cancer Center, from April to July 2023 and involved three distinct groups, ALL (n = 46), HL (n = 35), and healthy individuals (n = 30). Tissue samples were collected from patients, while blood samples from the control group. Data were retrieved from electronic medical records. The samples were analyzed for miR-206 expression and NF-κB1-94 ATTG polymorphism genotypes. miR-206 levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Genotypic distributions were determined through PCR and subsequent sequencing. Statistical analyses evaluated correlations between miR-206 levels, NF-κB1 genotypes, and clinical outcomes.</p><p><strong>Results: </strong>miR-206 expression was significantly lower in ALL patients compared to healthy controls (P < 0.0001), with mean values of 0.01 ± 0.1 in ALL, 0.01 ± 0.02 in HL, and 2,777.2 ± 31.55 in control subjects, suggesting a potential tumor suppressor role in ALL and HL. The genotypic distribution of the NF-κB1 (rs28362491) polymorphism revealed that homozygous Ins/Ins genotype was most prevalent in ALL compared with controls (41.3% vs 12%, P = 0.0048), and lowest in HL (28.5%). The heterozygous Ins/Del genotype was most prevalent in controls (60%), HL (42.8%), and least common in ALL (30.4%), indicating a possible protective effect against ALL. Further analysis showed no significant differences in miR-206 levels across the NF-κB1 genotypes (P = 0.9086) according to remission status for heterozygous Ins/Del and homozygous Del/Del compared to homozygous Ins/Ins.</p><p><strong>Conclusions: </strong>This study suggests that: 1) there was no significant difference in miR-206 expression across different NF-κB1-94 ATTG polymorphism genotypes; 2) reduced miR-206 expression could have a potential tumor suppressor role in ALL patients; 3) there was no significant genotype effect on remission status in ALL patients; and 4) both abnormalities could serve as biomarkers.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":"17 4","pages":"463-476"},"PeriodicalIF":2.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RAD51 in Breast Cancer: From Vulnerability to Resistance.","authors":"Rana Salman Anjum, Kazuaki Takabe","doi":"10.14740/wjon2764","DOIUrl":"10.14740/wjon2764","url":null,"abstract":"<p><p>Homologous recombination deficiency (HRD) has transformed the therapeutic landscape of breast cancer through the clinical success of poly(ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy. Central to this vulnerability is radiation sensitivity 51 (RAD51), the recombinase that executes homologous DNA repair and stabilizes stalled replication forks. In breast cancer susceptibility type 1 (BRCA1)- and breast cancer susceptibility type 2 (BRCA2)-mutant tumors, impaired RAD51 loading produces profound sensitivity to DNA-damaging agents. However, accumulating evidence indicates that restoration of RAD51 function-particularly its role in replication fork protection-is an important mechanism underlying therapeutic resistance. Beyond its canonical role in strand exchange-mediated double-strand break (DSB) repair, RAD51 orchestrates replication fork reversal, stabilization, and restart under conditions of oncogene-driven replication stress. These fork-associated functions can be mechanistically separable from classical homologous recombination and may be sufficient to confer resistance to PARP inhibitors even in tumors with persistent genomic scar signatures. Thus, breast cancer evolution under therapeutic pressure can be conceptualized as a transition from RAD51 deficiency-driven vulnerability to RAD51-dependent adaptive survival. In this review, we integrate structural, mechanistic, and translational insights into RAD51 biology and propose a dynamic framework in which replication fork protection represents a central adaptive axis in resistant breast cancer. We discuss functional biomarkers of RAD51 activity, subtype-specific dependency patterns, and emerging strategies to therapeutically target RAD51 in PARP inhibitor-refractory and replication stress-high disease. Understanding when RAD51 is deficient and when it becomes indispensable will be critical for refining precision oncology approaches in breast cancer. We argue that future precision oncology strategies must move beyond static HRD classification toward dynamic assessment of RAD51-dependent replication stress tolerance.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":"17 4","pages":"429-441"},"PeriodicalIF":2.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Transcriptomic Analysis Identifies Potential Biomarkers in Castration-Resistant Prostate Cancer.","authors":"Abdulghani A Naeem, Saud A Abdulsamad, Ateequllah Hayat, Ayesha Naeem, Nada Alhazmi, Ghaith Fallata, Anas Bokhari, Abdulmajeed H Alharbi, Kinani A Alkinani, Abdullah M Alshehri, Khadijah M Aldabbagh","doi":"10.14740/wjon2772","DOIUrl":"10.14740/wjon2772","url":null,"abstract":"<p><strong>Background: </strong>Castration-resistant prostate cancer (CRPC) represents an aggressive stage of prostate cancer that develops following resistance to androgen deprivation therapy. Although androgen receptor (AR) signaling remains a central driver of disease progression, additional adaptive molecular mechanisms contribute to therapeutic resistance. Understanding the transcriptional programs underlying CRPC may facilitate the identification of novel biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>RNA sequencing-based transcriptomic profiling was performed to compare a non-malignant prostate epithelial model (PNT2) with a CRPC model retaining AR expression (22Rv1). Differential gene expression analysis was conducted using DESeq2. Functional enrichment analyses were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Gene co-expression network analysis was applied to identify coordinated regulatory interactions. Clinical validation of candidate genes was performed using Gene Expression Profiling Interactive Analysis 2 (GEPIA2), integrating datasets from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project.</p><p><strong>Results: </strong>Transcriptomic comparison revealed extensive transcriptional remodeling associated with the castration-resistant phenotype. Several genes, including <i>MALAT1</i>, <i>FASN</i>, <i>PARP1</i>, <i>SET</i>, ENSG00000214719, and <i>IGF1</i>, were significantly dysregulated. Functional enrichment analyses demonstrated activation of metabolic processes, ribosome-associated pathways, nucleic acid binding functions, and PI3K-Akt signaling. Gene co-expression network analysis identified an AR-centered regulatory module involving <i>PARP1</i>, <i>KDM6B</i>, <i>BAZ2A</i>, <i>RANGAP1</i>, <i>NFAT5</i>, and <i>MAP4</i>. Clinical validation confirmed elevated expression of FASN, PARP1, SET, and ENSG00000214719 in prostate adenocarcinoma samples.</p><p><strong>Conclusions: </strong>Integrated transcriptomic and network analyses reveal coordinated metabolic, epigenetic, and DNA damage response pathways contributing to CRPC progression and identify potential combinatorial therapeutic vulnerabilities in advanced prostate cancer.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":"17 4","pages":"494-508"},"PeriodicalIF":2.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial Immune Remodeling Across the Gallbladder Carcinogenesis Spectrum: A Multicenter Digital Pathology Study.","authors":"Tamta Kveliashvili, George Didava, George Burkadze, Shota Kepuladze","doi":"10.14740/wjon2771","DOIUrl":"10.14740/wjon2771","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Gallbladder carcinoma (GBC) is the most aggressive malignancy of the biliary tract and is commonly associated with late diagnosis and early metastatic dissemination. Although the morphological sequence of gallbladder carcinogenesis from chronic inflammation to epithelial dysplasia and invasive carcinoma is well recognized, the role of the tumor immune landscape during this process remains insufficiently characterized. This study aimed to quantitatively evaluate immune microenvironment alterations across the spectrum of gallbladder lesions using immunohistochemistry and digital pathology analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective multicenter study was conducted using formalin-fixed paraffin-embedded gallbladder specimens collected between 2015 and 2026 from several collaborating hospitals and analyzed at the Department of Molecular Pathology, Tbilisi State Medical University. The study cohort included 90 cases representing chronic cholecystitis, intestinal metaplasia, biliary intraepithelial neoplasia (BilIN-1, BilIN-2, BilIN-3), and invasive gallbladder adenocarcinoma. Immunohistochemical analysis was performed for CD8 (cytotoxic T lymphocytes), FOXP3 (regulatory T cells), and CD163 (tumor-associated macrophages). Whole-slide digital image analysis using QuPath and ImageJ was applied to quantify immune cell densities and evaluate spatial distribution between tumor center and invasive tumor front compartments. Composite immune indices were calculated to integrate cytotoxic and immunosuppressive immune populations. The immune suppression index was defined as (FOXP3 + CD163)/CD8.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Quantitative analysis demonstrated progressive remodeling of the immune landscape across the spectrum of gallbladder lesions. CD8-positive cytotoxic lymphocytes were present in all lesion categories but showed heterogeneous density in invasive carcinoma. In contrast, FOXP3-positive regulatory T cells and CD163-positive macrophages demonstrated increased infiltration in dysplastic lesions and invasive tumors. Spatial analysis revealed preferential localization of CD8-positive lymphocytes at the invasive tumor margin with reduced infiltration of the tumor center, consistent with an immune exclusion pattern. Tumors associated with liver metastases exhibited lower cytotoxic lymphocyte density and increased infiltration by regulatory T cells and macrophages. Composite immune suppression indices were correspondingly elevated in metastatic tumors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Gallbladder carcinogenesis is associated with significant remodeling of the tumor immune microenvironment characterized by enrichment of immunosuppressive immune populations and spatial restriction of cytotoxic lymphocyte infiltration. Digital pathology-based quantification of immune architecture provides reproducible assessment of tumor-immune interactions and may contribute to the identification of immune-related biomarker","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":"17 4","pages":"524-533"},"PeriodicalIF":2.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct and Indirect Associations of Sociodemographic Factors and Patient-Perceived Barriers With Delayed Breast Cancer Presentation: A Cross-Sectional Path Analysis.","authors":"Juan Adrian Wiranata, Susanna Hilda Hutajulu, Yufi Kartika Astari, Angelica Abigael, Mardiah Suci Hardianti, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, Yayi Suryo Prabandari, Ibnu Purwanto","doi":"10.14740/wjon2754","DOIUrl":"10.14740/wjon2754","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Delayed presentation remains a contributor to advanced-stage breast cancer (BC) diagnosis and poor outcomes. Although sociodemographic factors are known to influence presentation delay, patient-perceived barriers may play a role in help-seeking behavior. However, the association linking sociodemographic characteristics, patient-perceived barriers, and delayed presentation remains insufficiently understood. This study aimed to examine the direct and indirect associations between sociodemographic factors, patient-perceived barriers, and delayed BC presentation using a path analysis approach.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This cross-sectional study included 150 women with BC. Sociodemographic characteristics, presentation interval, and patient-perceived barriers were collected through medical records and semi-structured interviews. Patient-perceived barriers were identified through content analysis of open-ended responses. Path analysis was conducted to estimate direct, indirect, and total effects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;None of the total indirect effects from sociodemographic variables to presentation delay through patient-perceived barriers were statistically significant. Five specific indirect pathways tested using the joint-significance approach were also non-statistically significant: age through fear of surgery (β = -0.002; P = 0.149), monthly income through fear of diagnosis (β = -0.029; P = 0.116), monthly income through fear of surgery (β = 0.047; P = 0.087), monthly income through preference for a female physician (β = 0.026; P = 0.135), and education through fear of surgery (β = 0.072; P = 0.051). Several sociodemographic factors showed significant direct associations with specific patient-perceived barriers. Increasing age was associated with lower fear of visiting health facilities (β = -0.245; P &lt; 0.05) and lower fear of surgery (β = -0.149; P &lt; 0.05). Higher income was associated with lower fear of diagnosis (β = -0.128; P &lt; 0.05), higher fear of surgery (β = 0.170; P &lt; 0.05), and greater preference for female physicians (β = 0.161; P &lt; 0.05). Lower educational attainment was associated with higher fear of surgery (β = 0.283; P &lt; 0.01), while unmarried status was associated with higher fear of healthcare costs (β = 0.383; P &lt; 0.01) and lower likelihood of seeking complementary and alternative medicine (β = -0.130; P &lt; 0.05). Several patient-perceived barriers were directly associated with delayed presentation, including fear of diagnosis (β = 0.165; P &lt; 0.01), fear of surgery (β = 0.247; P &lt; 0.01), painless symptoms (β = 0.367; P &lt; 0.001), symptom minimization (β = 0.105; P &lt; 0.05), perceived busyness (β = 0.244; P &lt; 0.01), and preference for female physicians (β = 0.105; P &lt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Although the hypothesized mediation of sociodemographic factors by patient-perceived barriers was not supported, several sociodemographic factors were associated with distinct ba","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":"17 4","pages":"454-462"},"PeriodicalIF":2.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Analysis of Ozanimod-Related Adverse Events Based on the FAERS Database.","authors":"Zi Ru Zhou, Qun Yan Zhou, Yue Shen, Xiao Yi Zhao, Qiang Zhan, Jing Sun, Zhong Xia Chen","doi":"10.14740/wjon2777","DOIUrl":"10.14740/wjon2777","url":null,"abstract":"<p><strong>Background: </strong>Ozanimod, a selective sphingosine-1-phosphate receptor modulator, has been approved for the treatment of moderately to severely active ulcerative colitis (UC) and relapsing forms of multiple sclerosis (MS). However, its postmarketing adverse event (AE) reporting profile requires further characterization.</p><p><strong>Methods: </strong>AE reports involving ozanimod from Q2 2020 to Q1 2025 were retrieved from the FDA Adverse Event Reporting System (FAERS) database. Frequency-based and Bayesian disproportionality methods were applied, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM), to identify pharmacovigilance reporting signals.</p><p><strong>Results: </strong>A total of 15,910 AE reports involving ozanimod were retrieved, of which 7,305 reports listed ozanimod as the primary suspected drug. Most reports involved patients aged 18-64 years (67.5%), and more reports were submitted for female patients than for male patients. Frequently reported events included fatigue, headache, dizziness, and back pain. Labeled or clinically recognized safety events, such as decreased lymphocyte count, decreased heart rate, hypertension, macular edema, and liver test abnormalities, were also detected as reporting signals. Disease-related Preferred Terms, including MS relapse, MS, UC, and proctitis ulcerative, showed strong disproportionality signals but may reflect underlying disease activity, treatment failure, indication, or reporting context rather than toxic adverse drug reactions. In addition, several hypothesis-generating FAERS signals not explicitly listed in current product labeling were observed, including depression, feeling of despair, decreased interest, penile swelling, and papillary thyroid cancer. These findings require cautious interpretation because FAERS cannot establish incidence, absolute risk, or causality.</p><p><strong>Conclusions: </strong>This study provides a postmarketing pharmacovigilance signal profile of AE reports involving ozanimod. The findings support continued monitoring of labeled safety concerns, careful interpretation of disease-activity-related reports, and further validation of selected unlabeled signals in prospective studies or better-controlled real-world datasets.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":"17 4","pages":"534-546"},"PeriodicalIF":2.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Epidermal Growth Factor Receptor 2 Negative, Low, and Overexpression in Breast Cancer Patients: Study on Recurrence-Free and Overall Survival.","authors":"Widyanti Soewoto, Kristanto Yuli Yarso, Ida Bagus Budhi Surya Adnyana, Wibisono Wibisono, Alifia Ramadhani Herida, Arie Assakandari, Diesta Maylitadara, Aldona Akhira Susanto, Azzahra Fadhlila Aulia Nisa, Cornelius Steve","doi":"10.14740/wjon2780","DOIUrl":"10.14740/wjon2780","url":null,"abstract":"<p><strong>Background: </strong>Human epidermal growth factor receptor 2 (HER2) expression is a key prognostic marker in breast cancer. Recently, HER2-low breast cancer has emerged as a potentially distinct subgroup; however, its prognostic significance remains controversial, particularly in real-world clinical settings. This study aimed to evaluate recurrence-free and overall survival (OS) across HER2 expression categories: HER2-negative, HER2-low, and HER2-overexpressing.</p><p><strong>Methods: </strong>This observational analytic study used a retrospective cohort design conducted at Dr. Moewardi Hospital, a tertiary referral center in Central Java, Indonesia. A total of 2,310 breast cancer patients with complete HER2 immunohistochemistry (IHC) results and documented survival data from 2018 to 2020 were included. HER2 status was classified as HER2-negative (IHC 0), HER2-low (IHC 1+ or IHC 2+ without amplification), and HER2-overexpression (HER2-positive). The primary outcome was OS, defined as the time from diagnosis to death from any cause. Survival was analyzed using the Kaplan-Meier method, with comparisons by log-rank test and risk estimation using Cox proportional hazards regression.</p><p><strong>Results: </strong>Of the patients, 43.6% were HER2-negative, 21.3% HER2-low, and 35.2% HER2-overexpressing. Kaplan-Meier analysis showed significant differences in OS among groups (log-rank χ² = 17.150; P < 0.001). HER2-negative patients had the best outcomes (mean OS 6.38 years; median unreached), followed by HER2-low (mean OS 5.60 years; median 4.00 years), and HER2-overexpression (mean OS 4.80 years; median 3.00 years). Significant differences were observed between HER2-negative vs. HER2-low (P = 0.015) and HER2-negative vs. HER2-overexpression (P < 0.001), but not between HER2-low and HER2-overexpression (P = 0.356). In Cox analysis, HER2-negative status reduced mortality risk by 22.2% compared with HER2-overexpression (hazard ratio 0.778; 95% confidence interval, 0.679-0.892; P < 0.001), while HER2-low showed no significant difference (hazard ratio 0.935; P = 0.413).</p><p><strong>Conclusions: </strong>HER2 expression is a significant prognostic factor in breast cancer. HER2-low patients have worse survival than HER2-negative patients and outcomes comparable to HER2-overexpression. These findings suggest that HER2-low breast cancer should not be considered low-risk and have important implications for prognostic stratification and treatment planning.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":"17 4","pages":"547-555"},"PeriodicalIF":2.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent Prognostic Impact of Histopathological Features and Combined Hematological-Biochemical Indices in Rectal Versus Colorectal Cancer: A Single-Center Study.","authors":"Vladica Cuk, Jovan Juloski, Marijana Gacinovic, Mirela Cuk, Radosav Radulovic, Jelena Grahovac","doi":"10.14740/wjon2787","DOIUrl":"10.14740/wjon2787","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer is frequently analyzed as a single disease entity despite recognized biological and clinical differences between colon and rectal tumors. This study investigated whether systemic inflammatory and nutritional indices demonstrate similar prognostic value in a pooled colorectal cancer cohort and in rectal adenocarcinoma analyzed separately.</p><p><strong>Methods: </strong>A predefined subgroup analysis of a previously established single-center cohort of surgically treated patients with long-term follow-up was performed. Prognostic associations of clinical, hematological, biochemical, and histopathological variables were evaluated in the overall colorectal cancer cohort and subsequently in patients with rectal adenocarcinoma using Kaplan-Meier and Cox regression analyses.</p><p><strong>Results: </strong>In the colorectal cancer cohort, severe postoperative complications (Clavien-Dindo III-V), higher lymph node ratio, tumor deposits, and modified Glasgow Prognostic Score 2 were independently associated with worse overall survival, while TNM stage, reduced peritumoral lymphocytic response, and tumor deposits predicted disease-free survival. In contrast, rectal adenocarcinoma demonstrated a distinct prognostic pattern: perineural invasion was associated with poorer overall survival in the exploratory rectal cancer subgroup analysis (hazard ratio (HR) = 25.125; P = 0.003), whereas platelet-to-lymphocyte ratio retained statistical significance with a modest effect size. Other systemic inflammatory and pathological parameters showed limited impact.</p><p><strong>Conclusions: </strong>Colon and rectal cancers exhibit divergent prognostic architectures. Combined analyses may reduce risk stratification accuracy and obscure the true value of inflammatory biomarkers, supporting the development of tumor site-specific prognostic models in colorectal oncology.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":"17 4","pages":"572-587"},"PeriodicalIF":2.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}