Cancers最新文献

{"title":"Primary Bone Vascular Neoplasms: An Integrated Biological Perspective from Bone Pathology to Precision Oncology.","authors":"Aikaterini Anetaki, Constantine Anetakis, Ioannis Chaniotakis, Christos Mpogiatzis, Anna Goussia, Dionysios J Papachristou, Mattheos Bobos","doi":"10.3390/cancers18193229","DOIUrl":"10.3390/cancers18193229","url":null,"abstract":"<p><p>Primary bone vascular neoplasms comprise a rare and biologically heterogeneous group of endothelial tumors encompassing benign, intermediate, and malignant entities with distinct clinicopathological, molecular, and prognostic characteristics. These tumors remain diagnostically and biologically challenging because of overlapping histopathological features, heterogeneous clinical behavior, evolving molecular landscapes, and limited disease-specific evidence. Advances in bone pathology, immunophenotyping, molecular diagnostics, and genomic profiling have substantially improved tumor classification and biological characterization. Importantly, contemporary classification and molecular studies have also highlighted the biological heterogeneity of vascular lesions involving bone, distinguishing well-defined vascular neoplasms from vascular malformations and identifying additional molecularly defined entities relevant to osseous disease and differential diagnosis. Concurrently, increasing recognition of the bone microenvironment and osteoimmunology provides a broader framework for understanding interactions among endothelial, skeletal, stromal, and immune populations and the extracellular matrix, with potential relevance to angiogenesis, bone remodeling, and tumor biology. Previous authoritative syntheses have established the classification, molecular features, diagnosis, and clinical management of these neoplasms. However, comparatively limited attention has been devoted to integrating tumor-intrinsic alterations with vascular-bone crosstalk, extracellular-matrix and mechanobiological signaling, osteoimmune regulation, and emerging precision-oncology strategies. Building on these foundations, this review integrates current evidence on classification, molecular pathogenesis, the skeletal microenvironment, osteoimmunology, biomarkers, and precision oncology. Where relevant, molecularly defined vascular neoplasms and vascular anomalies involving bone are discussed to clarify classification, molecular context, and differential diagnosis without conflating these lesions with the principal WHO-defined primary vascular neoplasms of bone. Findings directly demonstrated in primary bone vascular neoplasms are distinguished from mechanistic concepts extrapolated from physiological bone biology, other bone tumors, or non-osseous vascular neoplasms. Through this evidence-calibrated approach, we propose an integrated vascular-bone-immune framework, identify key knowledge gaps, and define priorities for disease-specific translational research and more individualized patient management.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognosis and Therapies in Non-Clear Cell Renal Cell Carcinomas.","authors":"Trilok Shrivastava, Yusra Medik, Nikhila Sampath Kumar, Shi-Ming Tu, Anuradha Kunthur","doi":"10.3390/cancers18193224","DOIUrl":"10.3390/cancers18193224","url":null,"abstract":"<p><strong>Background/objectives: </strong>Non-clear cell renal cell carcinoma (nccRCC) comprises biologically heterogeneous renal malignancies with distinct molecular drivers, clinical behavior, and therapeutic responses. This review summarizes prognosis and systemic therapy and evaluates emerging histology-specific and biomarker-directed approaches.</p><p><strong>Methods: </strong>We analyzed overall survival by histology in the SEER 17 Registries database (2000-2022) and conducted a narrative review of trials, guidelines, and translational studies. The ICD-O-3-defined population included 43,966 adults; 43,789 with known survival time were included in survival analyses.</p><p><strong>Results: </strong>Median follow-up was 96 months. Compared with papillary RCC, adjusted HRs were 0.67 (95% CI 0.64-0.70) for chromophobe RCC, 3.73 (3.37-4.11) for collecting duct carcinoma, 0.97 (0.80-1.17) for oncocytic tumors, and 33.23 (27.47-40.20) for medullary carcinoma. VEGFR- and MET-directed therapies and immune checkpoint inhibitor combinations show activity that varies by histology.</p><p><strong>Conclusions: </strong>nccRCC should be studied and managed as a collection of distinct entities. Registry associations require cautious interpretation because of residual confounding, evolving classification, and non-proportional hazards; subtype-specific trials and molecular stratification remain priorities.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in Somatic Mutations Between Early-Onset and Late-Onset Colorectal Cancer: A Systematic Review and Meta-Analysis.","authors":"Hui Lionel Raphael Chen, Jun Yan Ian Wee, Jun Kiat Thaddaeus Tan, Wei Ming Aaron Seah, Anders Jacobsen Skanderup, Chin-Ann Johnny Ong, Han Chong Toh, Kwong-Wei Emile Tan, Bee Huat Iain Tan","doi":"10.3390/cancers18193225","DOIUrl":"10.3390/cancers18193225","url":null,"abstract":"<p><strong>Background: </strong>Early-onset colorectal cancer (EOCRC, diagnosed <50 years) is increasing globally and presents with advanced clinicopathological features, yet its mutational landscape compared to late-onset CRC (LOCRC) remains poorly defined.</p><p><strong>Methods: </strong>We systematically searched PubMed and Embase (January 2016-December 2025) for studies comparing somatic mutations between EOCRC and LOCRC. Two reviewers independently screened 1880 records; 43 studies met inclusion criteria. Two public datasets (TCGA, China PanCancer) were also included. Meta-analyses were conducted using random-effects models with Review Manager. Subgroup analysis was restricted to microsatellite-stable (MSS) tumors. Meta-regression evaluated study-level differences in tumor sidedness and stage distribution as sources of heterogeneity. The primary outcome was odds ratios (OR) for mutations in 10 driver genes.</p><p><strong>Results: </strong>Among 154,982 participants, 33,937 (21.9%) had EOCRC. In the overall analysis, EOCRC showed higher frequencies of <i>TP53</i> (OR 1.13), <i>SMAD4</i> (OR 1.15), and <i>PTEN</i> mutations (OR 1.77), and lower frequencies of <i>APC</i> (OR 0.73), <i>KRAS</i> (OR 0.94), and <i>BRAF</i> mutations (OR 0.69). In MSS-restricted analysis, differences persisted for <i>TP53</i>, <i>SMAD4</i>, <i>APC</i>, and <i>KRAS</i>, whereas <i>PTEN</i> and <i>BRAF</i> differences became non-significant. Additionally, <i>NRAS</i> (OR 0.74) and <i>PIK3CA</i> mutations (OR 0.89) were less frequent in MSS-EOCRC. Meta-regression showed that study-level differences in left-sided tumor distribution were associated with lower relative BRAF mutation frequency in EOCRC (β = -5.08, 95% CI -7.66 to -2.49, <i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>EOCRC exhibits a different mutational profile with higher <i>TP53</i> and <i>SMAD4</i> and lower <i>APC</i> and <i>KRAS</i> mutations. These findings highlight the need for further research into alternative mechanisms of CRC carcinogenesis among younger adults.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>PODXL2</i> Expression Is Associated with Inferior Survival, Adverse-Risk Features, and Distinct Transcriptional Programs in Acute Myeloid Leukemia.","authors":"Hyun Min Ko, Katherine Scarton, Samantha C Covey, Lucio Miele, Sun Young Kim","doi":"10.3390/cancers18193219","DOIUrl":"10.3390/cancers18193219","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is characterized by substantial biological heterogeneity that is incompletely captured by current risk-classification frameworks. Podocalyxin-like 2 (<i>PODXL2</i>), a CD34-family transmembrane sialomucin implicated in tumor progression in solid tumors, remains poorly characterized in AML.</p><p><strong>Methods: </strong>We conducted integrated clinical, genomic, transcriptomic, regulatory network, and <i>ex vivo</i> drug-response analyses using two independent AML cohorts, TCGA-LAML and BeatAML.</p><p><strong>Results: </strong>Elevated <i>PODXL2</i> expression was consistently associated with inferior overall survival across both cohorts, including after adjustment for established clinical risk factors. <i>PODXL2</i>-high AML was enriched for adverse-risk features, including ELN 2022 adverse-risk classification, poor-risk cytogenetics, and <i>TP53</i> mutations, whereas <i>IDH2</i> mutations were more frequent in <i>PODXL2</i>-low AML. Transcriptomic analyses identified a distinct <i>PODXL2</i>-high state characterized by enrichment of MYC and E2F target programs, cell-cycle progression, DNA repair, oxidative phosphorylation, mTORC1 signaling, and metabolic pathways. Regulatory network analyses demonstrated enhanced MYC/E2F-associated regulatory activity. <i>PODXL2</i>-high AML also exhibited altered differentiation-state features, characterized by reduced representation of monocyte-like and conventional dendritic cell-like malignant cell states. <i>Ex vivo</i> drug-response profiling identified distinct <i>PODXL2</i>-associated response patterns, including reduced sensitivity to OTX-015 and SRC-family kinase inhibitors.</p><p><strong>Conclusions: </strong><i>PODXL2</i> expression is associated with adverse clinical and molecular features, distinct transcriptional programs, altered differentiation states, and differential <i>ex vivo</i> drug-response patterns in AML. These findings identify <i>PODXL2</i> expression as a marker associated with adverse clinical and molecular features and inferior survival in AML, although its prognostic discrimination as a standalone marker is modest. Further functional and prospective studies are warranted to establish its biological and clinical significance.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic Endonasal Approaches to Anterior Cranial Base Meningiomas: Indications, Limitations, and Surgical Decision-Making.","authors":"Manat Chopra, David John, David J Cote, Gabriel Zada","doi":"10.3390/cancers18193217","DOIUrl":"10.3390/cancers18193217","url":null,"abstract":"<p><p>Endoscopic endonasal surgery (EES) has fundamentally changed the management of anterior skull base meningiomas by enabling access to many lesions through a direct minimally invasive corridor that avoids traditional transcranial exposure. Improvements in endoscopic optical technology, surgical instrumentation, and skull base reconstruction have steadily expanded the range of tumors that can be treated through an endonasal approach. Even so, EES is not appropriate for every lesion, making thoughtful patient selection and surgical team experience the most important determinants of surgical success. This review explores where EES fits in the contemporary management of anterior skull base meningiomas, including olfactory groove, tuberculum sellae, and planum sphenoidale meningiomas, with particular attention to its indications, limitations, and situations in which EES may not be appropriate. Evidence comparing endoscopic endonasal and transcranial approaches for anterior skull base meningiomas is reviewed, with attention to how tumor anatomy, oncologic objectives, and individual patient characteristics influence the choice of approach. A major consideration is how surgical morbidity can be minimized without compromising oncologic and safety outcomes. Current strategies to protect critical neurovascular structures, reduce the risk of cerebrospinal fluid leakage, and improve skull base durability, including advances in vascularized reconstruction techniques, are discussed. Emerging outcome data and the evolving learning curve associated with EES are also reviewed. Rather than presenting EES as a universal solution, the evidence points toward a patient-centered approach in which operative strategy and clinical decision making is guided by tumor characteristics, anatomy, and surgical goals.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Molecular Alterations to Risk Prediction: Biomarkers of Actinic Keratosis Progression to Cutaneous Squamous Cell Carcinoma.","authors":"Thomas Meyer, Lea Stockfleth, Kerstin Lang, Heiko U Käfferlein, Thomas Brüning, Eggert Stockfleth","doi":"10.3390/cancers18193221","DOIUrl":"10.3390/cancers18193221","url":null,"abstract":"<p><p>The high-and in most countries steadily increasing-incidence of cutaneous squamous cell carcinoma (cSCC) represents a growing public health challenge. As the majority of cSCCs arise from pre-existing actinic keratosis (AKs), these lesions are recognized as the principal precursors of invasive disease. A comprehensive understanding of the molecular mechanisms driving the progression from AK to cSCC is essential for advancing prevention, facilitating early diagnosis, and enabling targeted therapies. Moreover, this knowledge provides a basis for identifying biomarkers that can predict the risk of malignant transformation. The progression from AK to cSCC is a complex, multistep process driven by the gradual accumulation of genetic, epigenetic, and microenvironmental alterations. Over the past decades, numerous molecular changes associated with this transition have been identified. However, no single biomarker has demonstrated sufficient predictive accuracy for clinical use. This reflects the pronounced molecular heterogeneity of AKs as no individual alteration is uniformly present in all lesions that undergo malignant progression. In addition, numerous proposed biomarkers are also detected in non-progressive AKs and even in non-neoplastic skin, which compromises their sensitivity and specificity for predicting progression to cSCC. Current evidence, therefore, suggests that the most promising strategy for identifying AKs at greatest risk of malignant transformation is the development of a multi-marker panel. This panel, ideally, should integrate molecular signatures encompassing genetic, epigenetic, proliferative, inflammatory, and microenvironmental markers. This review summarizes the molecular factors that currently represent the most promising candidates for inclusion in such a multi-marker panel and discusses their potential clinical utility, while emphasizing the need for validation in well-designed prospective longitudinal studies.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gleason Pattern 4 Burden and Adverse Pathology in ISUP Grade Group 2 Prostate Cancer: Implications for Active Surveillance Selection.","authors":"Lucas Regis, Clara Perez, Jacques Planas, Ana Celma, Merce Cuadras, Maria-Eugenia Semidey, Richard Mast, Juan Morote, Enrique Trilla","doi":"10.3390/cancers18193222","DOIUrl":"10.3390/cancers18193222","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Active surveillance (AS) is increasingly considered for selected patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 2 prostate cancer. However, candidate selection remains controversial due to histological heterogeneity and the risk of harboring adverse pathology (AP). We aimed to identify preoperative clinical, multiparametric magnetic resonance imaging (mpMRI), and histological predictors of AP, biochemical recurrence (BCR), and postoperative PSMA PET/CT positivity in men with biopsy-confirmed ISUP GG 2 disease undergoing robotic-assisted radical prostatectomy (RARP).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We retrospectively analyzed 127 consecutive patients with biopsy-proven ISUP GG 2 prostate adenocarcinoma from a prospective single-center RARP database (2012-2024). All patients underwent pre-biopsy 3T mpMRI and systematic plus software-fusion targeted biopsies, with diagnostic specimens strictly lacking cribriform architecture or intraductal carcinoma. AP was defined as pathological stage ≥ pT3 and/or ISUP GG upgrading to ≥3 in the final surgical specimen. BCR was defined as two consecutive postoperative PSA measurements ≥ 0.2 ng/mL. Patients with BCR underwent PSMA PET/CT restaging. Univariable and multivariable logistic regression analyses evaluated independent preoperative predictors of AP, incorporating separate models for ≥10% and ≥15 biopsy Gleason pattern 4 thresholds to prevent collinearity. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow calibration tests.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Median patient age was 63.2 years, median PSA was 7.6 ng/mL, and median PSA density (PSAD) was 0.18 ng/mL. PI-RADS ≥ 4 lesions were identified in 71.6% of patients, and median biopsy pattern 4 proportion was 21.1%. Overall, AP occurred in 39 of 127 patients (30.7%), driven by ISUP upgrading to GG ≥ 3 in 21.3% (n = 27) and upstaging to ≥pT3 in 17.3% (n = 22). No undergrading was observed. On univariable analysis, PSA (&lt;i&gt;p&lt;/i&gt; = 0.028), PSAD (&lt;i&gt;p&lt;/i&gt; = 0.011), and biopsy pattern 4 proportion ≥ 10% (&lt;i&gt;p&lt;/i&gt; = 0.042) and ≥15% (&lt;i&gt;p&lt;/i&gt; = 0.027) were significantly associated with AP. On multivariable analysis, PSAD (OR 6.75, 95% CI 3.51-12.87, &lt;i&gt;p&lt;/i&gt; = 0.005) and biopsy pattern 4 proportion ≥ 10% (OR 2.54, 95% CI 1.15-6.54, &lt;i&gt;p&lt;/i&gt; = 0.036) or ≥15% (OR 2.74, 95% CI 1.06-6.06, &lt;i&gt;p&lt;/i&gt; = 0.023) remained independent predictors of AP. The final multivariable model demonstrated solid discrimination (AUC = 0.78, 95% CI 0.71-0.85) and satisfactory calibration (&lt;i&gt;p&lt;/i&gt; = 0.42). At a mean follow-up of 32.3 months, BCR occurred in 23 patients (18.1%; 3-year recurrence-free survival: 81.3%). Restaging PSMA PET/CT was positive in 8 of 23 recurrences (34.8%; three local, four regional nodal, one solitary bone). Neither clinical nor radiological parameters independently predicted BCR or PSMA PET/CT positivity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conc","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GSTT2 Switches from a Homeostatic Antioxidant to a Cell-Cycle-Coupled Factor in Therapy-Resistant Esophageal Adenocarcinoma.","authors":"Daysha Ferrer-Torres, Paramita Ray, Noah Etzioni, Max A Hammer, Archismaan Ghosh, Meilan Liu, Vinay Jeeyar, Sachin Wani, Sunnie S Kim, Benedetto Mungo, Stefan Marasligiller, Danielle Kim Turgeon, Jules Lin, Peter D R Higgins, Jason R Spence, Kiran H Lagisetty, David G Beer, Dipankar Ray","doi":"10.3390/cancers18193220","DOIUrl":"10.3390/cancers18193220","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Glutathione S-transferase theta 2 (GSTT2) is highly expressed in esophageal tissues from African American (AA) compared with European American (EA) individuals, but its localization, regulation, and relevance to esophageal adenocarcinoma progression remain unclear. <b>Methods:</b> Here, we combined FISH, immunofluorescence, patient-derived culture models, cell-cycle synchronization, biochemical perturbation, and transcriptomics to define GSTT2 expression in normal and neoplastic esophageal contexts. <b>Results:</b> In developing and adult esophageal tissues, GSTT2 mRNA and protein were broadly distributed across squamous epithelium and lamina propria, co-localizing with p63-positive basal/progenitor cells and extending into differentiated compartments, with no major ancestry-associated differences in spatial patterning. In Barrett's esophagus, GSTT2 protein was retained in metaplastic columnar epithelium and slightly elevated in dysplastic versus adjacent non-dysplastic regions. GSTT2 mRNA was highest in normal squamous esophagus, reduced during Barrett's-to-adenocarcinoma progression, but increased in treatment-resistant esophageal adenocarcinoma (EAC). In resistant EAC, GSTT2 co-expression shifted from homeostatic antioxidant programs to proliferation and mitotic pathways, including the G2-M checkpoint, E2F targets, and Reactome Cell Cycle, with leading-edge regulators CDK1 and CDC20. Sequence analysis identified putative APC-C and FBXW7 recognition motifs. In synchronized cells, GSTT2 abundance declined during S-G2/M and increased during mitotic exit/early G1 in cytosolic and membrane fractions. Forskolin, a dual inhibitor of FBXW7 and CDC20, stabilized GSTT2 and rescued CDC20- or FBXW7-associated loss, implicating APC-CDC20 and FBXW7 pathways in GSTT2 turnover. In EAC cells, by contrast, CDC20 was found to be a cooperative partner stabilizing GSTT2. <b>Conclusions:</b> These findings identify GSTT2 as a spatially widespread, ancestry-associated, cell-cycle-regulated protein with potential oncogenic roles in EAC resistance.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpretable CT-Based Radiomics for Prediction of High-Affinity Neoantigens Associated Immunogenic States in Advanced Hepatocellular Carcinoma Treated with TACE Plus Targeted Therapy and Immunotherapy.","authors":"Chaofan Bian, Yanjin Qin, Hongliang Zou, Wenzhe Fan, Jiaping Li","doi":"10.3390/cancers18193218","DOIUrl":"10.3390/cancers18193218","url":null,"abstract":"<p><p><b>Objectives:</b> To develop and validate a CT radiomics-based machine learning model for the noninvasive prediction of HANS status in advanced HCC and to investigate the prognostic and genomic characteristics associated with HANS status. <b>Materials and Methods:</b> This retrospective study included patients with advanced HCC treated with TACE-based triplet therapy. Patients were followed until death or last follow-up. Tumor tissue underwent whole-exome sequencing for HANS calculation, and arterial-phase CT images were used for radiomic feature extraction. A radiomics model (HANS-Rad), a clinical model (HANS-Clin), and a combined model (HANS-RC) were developed using least absolute shrinkage and selection operator regression. Model performance was evaluated using receiver operating characteristic curve analysis. Calibration and decision curve analyses were performed to assess model reliability and clinical utility. Shapley Additive Explanations (SHAP) were used for model interpretation. Genomic analyses were conducted to explore differences between predicted HANS subgroups. <b>Results:</b> A total of 129 patients were included (median age, 54 years; IQR, 44-62 years; 90% men). The HANS-High group demonstrated longer overall survival compared with the HANS-Low group (median, 23.0 vs. 10.0 months; hazard ratio, 0.60; <i>p</i> = 0.026). The combined HANS-RC model achieved the best performance, with an area under the curve (AUC) of 0.964 in the training set and 0.869 (95% CI, 0.716-1.000) in the test set, outperforming the radiomics-only and clinical models. The model also showed favorable calibration and net benefit. Genomic analyses revealed that HANS-High tumors exhibited higher tumor mutational burden and enrichment of immune-related and oncogenic pathways, whereas HANS-Low tumors were associated with distinct mutational patterns and pathway alterations. <b>Conclusions:</b> A radiomics-based machine learning model using CT images enables the noninvasive prediction of HANS status in advanced HCC, with strong prognostic relevance and biologic interpretability supported by genomic analyses.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PET Tumour Segmentation in Head and Neck Cancer: Reproducibility, Reader Dependence and Concordance with CT-Defined Tumour Volume in a 154-Patient Cohort.","authors":"Anne-Sophie Pirson, Gilles Delahaut, Raphaël Georis, Stéphanie Deheneffe, Sébastien Van der Vorst, Ken Kudura","doi":"10.3390/cancers18193214","DOIUrl":"10.3390/cancers18193214","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Volumetric PET biomarkers carry substantial prognostic value in head and neck squamous cell carcinoma (HNSCC), yet their clinical implementation is hampered by segmentation heterogeneity. A fundamental and unresolved question is which segmentation method is most suitable for routine clinical use, both for a reader experienced in PET segmentation and for a reader without PET segmentation experience, such as an ENT surgeon or a radiation oncologist. This study addressed this question by assessing the intra- and interobserver reproducibility of four PET segmentation methods in MIM Maestro Software Version 7.4.2, identifying tumour-related determinants of variability, and examining concordance between PET-derived metabolic tumour volume (MTV) and CT-based gross tumour volume (GTV). &lt;b&gt;Methods:&lt;/b&gt; Two readers with contrasting PET segmentation experience, a nuclear medicine physician experienced in PET segmentation (R1) and an ENT surgeon without prior PET segmentation training (R2), applied four methods to the primary tumours of 154 patients with HNSCC (oral cavity, oropharynx, hypopharynx or larynx) treated with definitive (chemo)radiotherapy between 2010 and 2021: fixed absolute thresholds at SUV 3.0 and 4.0, a relative threshold at 41% of the maximum standardised uptake value (SUVmax), and a gradient edge-detection algorithm (PET Edge+). R1 segmented twice with a washout of at least 4 weeks; R2 performed one session and delineated CT-GTV in the 85 patients whose PET/CT-derived CT served directly as the radiotherapy planning scan. The second session of R1 served as the reference for all interobserver and MTV-GTV analyses. Agreement was assessed by ICC (two-way mixed model), coefficient of variation, repeatability coefficient and Bland-Altman analysis; determinants of variability by a multivariable linear mixed-effects model with a random intercept per patient. &lt;b&gt;Results:&lt;/b&gt; All four methods demonstrated excellent intraobserver (ICC 0.993 to &gt;0.999) and interobserver (ICC 0.989-0.996) reproducibility. SUV3.0 generated significantly more relative error than SUV41% (β = +3.1%; 95% CI 0.89, 5.3). PET Edge+ was the only method for which a significant method × reader interaction was observed in this reader pair: the reader without PET segmentation experience generated more error than the reader experienced in PET segmentation (β = +7.1%; 95% CI 3.9, 10), an effect concentrated in smaller tumours (below approximately 15 mL); in the 85-patient GTV subset, where tumours were larger on average, the interobserver ICC for PET Edge+ was 0.997. GTV concordance was good for three of four methods (ICC 0.808-0.895); SUV41% showed only moderate concordance (ICC 0.572). &lt;b&gt;Conclusions:&lt;/b&gt; All four methods provided excellent volumetric reproducibility within a single clinical software platform, but they differed in reader dependence and in agreement with CT-defined GTV. Rather than supporting a universal segmentation standard, these findings s","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}