Discover. Oncology最新文献

{"title":"Immune-related hallmark pathway heterogeneity identifies a prognostic risk signature with independent external validation in glioblastoma.","authors":"Ahmed M Abdelmaguid, Rasha M A Eltanany, Manal F El-Khadragy, Ahmed E Abdel Moneim","doi":"10.1007/s12672-026-05696-5","DOIUrl":"10.1007/s12672-026-05696-5","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most aggressive primary malignant brain tumor in adults and remains associated with poor clinical outcomes despite advances in surgery, radiotherapy, and chemotherapy. Increasing evidence suggests that the glioblastoma immune microenvironment and coordinated oncogenic signaling pathways play critical roles in tumor progression, therapeutic resistance, and survival heterogeneity. However, the prognostic relevance of pathway-level immune activity in GBM remains incompletely understood. In this study, we performed a comprehensive transcriptomic and pathway-centered analysis of glioblastoma using RNA-sequencing data and clinical information obtained from The Cancer Genome Atlas (TCGA-GBM) cohort. Single-sample gene set enrichment analysis (ssGSEA) was applied to quantify hallmark pathway activity across tumors, followed by immune subtype clustering, survival analysis, Cox regression modeling, machine learning-based pathway prioritization, and prognostic risk signature construction. The reproducibility of the developed prognostic model was subsequently evaluated using an independent Chinese Glioma Genome Atlas (CGGA) validation cohort. Our analysis demonstrated substantial inter-patient variability in immune-related and oncogenic hallmark signaling pathways. Inflammatory and mesenchymal-associated pathways, including TNF-α/NF-κB signaling, IL6/JAK/STAT3 signaling, interferon responses, epithelial-mesenchymal transition, hypoxia, complement activation, and KRAS signaling, showed marked differences across patients and were strongly associated with aggressive disease phenotypes. Two immune-associated molecular subtypes with distinct pathway activation patterns were identified. Furthermore, multiple hallmark pathways demonstrated significant prognostic associations and were integrated into a pathway-derived prognostic risk signature that successfully stratified patients into high-risk and low-risk groups with significantly different overall survival outcomes. Multivariate Cox regression analysis confirmed that the calculated risk score retained independent prognostic significance after adjustment for clinical variables. Importantly, external validation using the CGGA cohort demonstrated stable prognostic performance and reproducibility across independent patient populations. Taken together, these findings demonstrate that immune-related hallmark pathway activity contributes substantially to glioblastoma biological heterogeneity and patient prognosis. The proposed pathway-based prognostic framework provides a biologically interpretable approach for survival stratification and may support future efforts toward precision oncology and pathway-oriented therapeutic investigation in glioblastoma.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA DLGAP1-AS2 promotes ESCC progression and indicates unfavorable prognosis via the miR-101-3p/EZH2 axis.","authors":"Liwei Tang, Yichuan Zhang, Xiangting Cheng","doi":"10.1007/s12672-026-05785-5","DOIUrl":"10.1007/s12672-026-05785-5","url":null,"abstract":"<p><strong>Objective: </strong>LncRNAs are crucial regulators and biomarkers in various cancers. However, their expression and functions in esophageal squamous cell carcinoma (ESCC) remain largely unexplored. This study explored the clinial relevance and mechanisms of LncRNA DLGAP1-AS2 in ESCC.</p><p><strong>Methods: </strong>Utilizing the GEO dataset, the identification of differentially expressed lncRNAs in ESCC encompassed DLGAP1-AS2. RT-qPCR was employed to measure its expression in 135 paired tumors and adjacent non-cancerous tissue samples. Patients were followed up for five years. Kaplan-Meier curves and Cox regression analysis evaluated DLGAP1-AS2's prognostic impact, while CCK-8 and Transwell assays assessed cell proliferation. Additionally, commercial assay kits measured ROS, MDA, GSH, and iron levels. DLR and RIP assays confirmed miR-101-3p targeting DLGAP1-AS2 and EZH2.</p><p><strong>Results: </strong>DLGAP1-AS2 was markedly upregulated in ESCC tumor tissues and cell lines. High expression of DLGAP1-AS2 correlated with advanced clinical stages and extensive lymph node metastasis in ESCC patients, and patients with elevated DLGAP1-AS2 expression had a worse prognosis. Mechanistically, DLGAP1-AS2 competitively binds miR-101-3p, upregulating EZH2. Depleting DLGAP1-AS2 significantly curbed ESCC cell proliferation, migration, invasion, and EMT, while boosting ferroptosis-an effect notably reversed by miR-101-3p reduction.</p><p><strong>Conclusion: </strong>DLGAP1-AS2 acts as a potential biomarker for unfavorable prognosis in ESCC patients. Mechanistically, it promotes malignant phenotypes of ESCC cells in vitro by regulating the miR-101-3p/EZH2 axis, enhancing proliferation and EMT, while suppressing ferroptosis.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Current evidence and emerging approaches in immunotherapy for gynecological cancers.","authors":"Victory Jesutoyosi Ashonibare, Oluwaseun Samuel Hezekiah, Omotola Seunfunmi Kukoyi, Suliat Adenike Hassan, Olaoluwa Ayoade Afolabi, Tunmise Maryanne Akhigbe, Roland Eghoghosoa Akhigbe","doi":"10.1007/s12672-026-05823-2","DOIUrl":"10.1007/s12672-026-05823-2","url":null,"abstract":"","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Resveratrol synergizes with cisplatin to suppress osteosarcoma U2-OS cells via up-regulating Cx43 and inducing ROS-dependent apoptosis.","authors":"Hong-Bo Xing, Hao-Yu Li, Gui-Zhou Zheng, Qi-Hao Zhang, Lei Zhai, Xiang Wu, Shi-Xin Du, Xue-Dong Li","doi":"10.1007/s12672-026-05187-7","DOIUrl":"10.1007/s12672-026-05187-7","url":null,"abstract":"","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: A case study of gastritis cystica profunda mimicking a submucosal tumor treated with endoscopic submucosal dissection.","authors":"Ya-Li Wang, Chen-Fei Liang, Yan-Li Cheng","doi":"10.1007/s12672-026-04557-5","DOIUrl":"10.1007/s12672-026-04557-5","url":null,"abstract":"","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"pH responsive nanoplatforms for radiosensitization and radioprotection in cancer therapy.","authors":"Enhui Dai, Yiqin Qiu, Huan Xu, Guoqiang Zhong, Wei Feng","doi":"10.1007/s12672-026-05781-9","DOIUrl":"10.1007/s12672-026-05781-9","url":null,"abstract":"<p><p>Radiotherapy remains a cornerstone of cancer treatment, but its efficacy is limited by tumor hypoxia, adaptive antioxidant defenses, and the resulting radioresistance. Tumor extracellular acidity, commonly reported within an approximate pH range of 6.5-7.1, contributes to invasion, immune suppression, and treatment resistance while also providing a recurrent, although nonexclusive, stimulus for responsive nanoplatform design. This narrative review critically examines pH-sensitive nanoplatforms that function as molecular switches by altering their structure, surface charge, assembly state, or payload accessibility under acidic conditions. The principal chemical strategies include acid-labile bond cleavage, pH-induced charge reversal, conformational gatekeeping, and ultra-pH-sensitive polymeric probes. Their radiotherapy-specific effects depend on the associated payload or inorganic component and may include increased tumor retention of high-Z materials, catalytic reactive oxygen species amplification, enhanced DNA damage, ferroptosis, cGAS-STING-mediated immune activation, and improved oxygen availability. The strength of evidence varies substantially among applications. Direct preclinical radiosensitization has been demonstrated for selected acid-triggered metal and gold nanoparticle systems, whereas many linker-based, nucleic-acid-gated, ferroptosis-inducing, and oxygen-delivering platforms remain supported mainly by complementary mechanistic studies or non-radiotherapy evidence. Nanoparticle-based radionuclide delivery and dual-responsive systems have also been investigated preclinically, although direct evidence for pH-gated renal sparing remains limited. The integration of pH-sensitive nanoplatforms with FLASH radiotherapy remains a conceptual and computationally informed direction without direct clinical validation. Beyond radiosensitization, pH-responsive gastrointestinal formulations have shown normal-tissue radioprotection in animal models, but tumor-selective reverse-switch nanoradioshields remain largely conceptual. Theranostic integration with MRI-CEST, acidity-sensitive PET, or Cherenkov-based sensing may support future image-guided treatment adaptation, but pH-informed dose painting has not yet been clinically validated. Clinical translation is further constrained by intratumoral pH heterogeneity, potential activation in inflammatory or ischemic tissues, protein-corona effects, manufacturing variability, uncertain pharmacokinetics, regulatory complexity, and the need to synchronize nanoparticle activation with irradiation. Progress will require compartment-specific switching, matched nonresponsive controls, patient-selection biomarkers, scalable manufacturing, and prospective demonstration of improved tumor control without unacceptable normal-tissue toxicity.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating locoregional therapy with systemic and emerging cellular therapies in advanced intrahepatic cholangiocarcinoma.","authors":"Lihua Zhang, Mengqi Zhang, Zengjin Wen, Xiaoxuan Li, Wensheng Qiu","doi":"10.1007/s12672-026-05832-1","DOIUrl":"10.1007/s12672-026-05832-1","url":null,"abstract":"<p><p>Advanced intrahepatic cholangiocarcinoma (ICC) may be liver-confined or liver-dominant after curative resection is no longer feasible. This distribution supports a role for locoregional therapy (LRT), whereas occult or established extrahepatic disease still requires systemic control. This narrative review integrates the most recent clinical and mechanistic evidence for combining LRT with chemotherapy, immune checkpoint inhibition, molecularly targeted treatment, and cellular therapy. Randomized phase III biliary tract cancer trials support gemcitabine-cisplatin plus durvalumab or pembrolizumab as first-line systemic therapy, but the primary analyses improved median overall survival by only 1.3 and 1.8 months. Evidence for adding LRT is less mature and heterogeneous. Prospective single-arm studies of yttrium-90 radioembolization, hepatic arterial infusion, radiotherapy, and cryoablation-based combinations report activity in selected ICC populations, but most lack a contemporary control and cannot isolate the contribution of LRT. No biomarker has validated the incremental benefit of a specific LRT. Clinical development should therefore specify the LRT modality and exposure, disease distribution, systemic backbone, treatment intent, and safety boundary. Routine adoption requires reproducible protocols, comparative survival and safety endpoints, and paired biomarker collection.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative transcriptomic analysis identifies shared coding and non-coding biomarkers in tongue squamous cell carcinoma across diverse populations.","authors":"Ronit Roy, Monika Rajput, Manoj Pandey","doi":"10.1007/s12672-026-05428-9","DOIUrl":"10.1007/s12672-026-05428-9","url":null,"abstract":"<p><strong>Background: </strong>Tongue cancer, a prevalent subtype of oral malignancy, remains a significant global health burden with high morbidity and mortality, particularly in developing countries. Understanding its molecular landscape is crucial for developing targeted diagnostics and therapeutics.</p><p><strong>Objective: </strong>This systematic review aimed to identify common differentially expressed protein-coding genes (DEGs) in tongue cancer across multiple populations and explore their functional significance through integrative bioinformatic analyses.</p><p><strong>Methods: </strong>We performed an integrative meta-analysis of transcriptomic datasets from China, the USA, and Australia to identify common differentially expressed genes (DEGs). Functional enrichment, protein-protein interaction (PPI), and regulatory network analyses were conducted. Crucially, the clinical relevance of identified hub genes was validated using the TCGA-HNSC cohort to assess correlations with tumor stage and overall survival.</p><p><strong>Results: </strong>A total of 133 common DEGs were identified, primarily enriched in extracellular matrix (ECM) disassembly, collagen catabolism, and IL-17 signaling. Key hub genes included MMP3, MMP10, COL1A1, CDKN2A, and CXCL11. Network analysis uncovered novel lncRNAs, including TENM3-AS1 and DUXAP10, regulating immune and epithelial pathways. Clinical validation demonstrated that high expression of STC2 and MMP3 significantly correlated with advanced tumor stage (p < 0.05). Furthermore, STC2 upregulation was identified as a significant predictor of poor overall survival (p = 0.0037).</p><p><strong>Conclusion: </strong>This study defines a cross-population gene signature driving TSCC through ECM remodeling and immune modulation. The validation of STC2 as a prognostic marker highlights its potential for clinical risk stratification.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiological risk factors and inferred p53 pathway dysregulation in Esophageal squamous cell carcinoma in the Somali population.","authors":"Hashim Mohamed Rooraye, Yusuf Lukman, Rapeah Suppian, Akbar Ali, Che Ismail Che Lah, Ramiza Ramza Ramli","doi":"10.1007/s12672-026-04475-6","DOIUrl":"10.1007/s12672-026-04475-6","url":null,"abstract":"<p><strong>Introduction: </strong>Esophageal squamous cell carcinoma (ESCC) is the most prevalent cancer in Somalia and constitutes a major public health concern in the Horn of Africa. Despite its high incidence, the molecular mechanisms underlying ESCC are not well characterized. This scoping review synthesizes published data on TP53 mutations, environmental and lifestyle risk factors, and the epidemiology of ESCC to identify knowledge gaps and guide future research.</p><p><strong>Methods: </strong>The review was conducted in accordance with the PRISMA-ScR guideline and the Joanna Briggs Institute framework. A structured search was performed in PubMed, Scopus, Embase, and Google Scholar.</p><p><strong>Results: </strong>Twenty studies met the inclusion criteria. ESCC was consistently identified as the leading cancer, representing up to one-third of all malignancies in Somali and neighbouring populations, with most cases diagnosed at advanced stages. Molecular evidence was limited; no sequencing-based studies from Somalia were identified. However, immunohistochemical data indicated p53 overexpression in approximately 60-70% of ESCC cases, suggesting frequent TP53 pathway disruption. Regional studies reported TP53 mutation rates of 50-70%, lower than the 90% observed in high-incidence Asian populations. Key environmental exposures, including khat chewing, co-exposure to aflatoxin and fumonisin, biomass fuel smoke, polycyclic aromatic hydrocarbons, and consumption of very hot beverages, were strongly associated with increased ESCC risk.</p><p><strong>Conclusion: </strong>This review demonstrates a substantial but poorly characterized burden of ESCC in the Horn of Africa, driven by distinct environmental and cultural exposures. Frequent TP53 pathway disruption is evident, yet genomic data remain scarce. Integrating exposure assessment with molecular profiling and enhancing food safety, clean cooking practices, and culturally tailored prevention strategies are essential to reduce ESCC incidence in the region.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148825196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Organizing pneumonia in ALK⁺ non-small cell lung cancer treated with ceritinib: a case report.","authors":"Xiao Lin, Mengyao Xie, Dandan Ma, Dandan Zheng, Jingjing Liu, Jinyan Ye, Lehe Yang, Yao Lu","doi":"10.1007/s12672-026-04810-x","DOIUrl":"10.1007/s12672-026-04810-x","url":null,"abstract":"","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}