Tumor Biology最新文献

{"title":"Beyond proficiency testing: Leveraging commutable External Quality Assessment data to harmonize tumor markers and refine medical decision points.","authors":"Jong Do Seo, Huub H Van Rossum, Yeo-Min Yun","doi":"10.1177/14230380261472771","DOIUrl":"https://doi.org/10.1177/14230380261472771","url":null,"abstract":"<p><p>BackgroundSerum tumor markers such as carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and prostate-specific antigen (PSA) are crucial to clinical decision-making based on defined medical thresholds. However, significant inter-method variability and lack of harmonization limit result comparability and hinder consistent application of international guidelines.ObjectiveThis letter proposes an expanded role for External Quality Assessment (EQA) programs as active drivers of assay harmonization beyond conventional proficiency testing.MethodsThis proposal draws on recent studies evaluating the commutability of frozen human serum pools (FSPs) from the Korean Association of External Quality Assessment Service (KEQAS) and findings from EQA-based harmonization simulations. It demonstrated that harmonization of tumor markers such as CA 15-3 and CEA, is achievable.ResultsKEQAS FSPs demonstrated commutability for AFP, CEA, and total PSA across major diagnostic platforms. Simulation results indicated that \"in silico\" recalibration substantially reduced inter-method variability; for example, the bias range for CA 15-3 was reduced from [-29.28%, 9.86%] to [-0.09%, 0.12%], and recalibrating outlier methods for CEA improved the alignment also.ConclusionsEQA programs can serve as practical harmonization hubs by leveraging commutable materials and implementing EQA-driven recalibration. Such approaches can help that medical decision points, retain consistent clinical significance across diverse analytical systems.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"48 ","pages":"14230380261472771"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: \"MicroRNA-337 inhibits cell proliferation and invasion of cervical cancer through directly targeting specificity protein 1\".","authors":"","doi":"10.1177/14230380261450003","DOIUrl":"https://doi.org/10.1177/14230380261450003","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"48 ","pages":"14230380261450003"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147989367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardization of prostate-specific antigen assays: Impact on reference intervals and clinical decision thresholds.","authors":"Xavier Filella","doi":"10.1177/14230380261466593","DOIUrl":"https://doi.org/10.1177/14230380261466593","url":null,"abstract":"<p><p>BackgroundProstate-specific antigen (PSA) remains the most widely used biomarker for prostate cancer screening, diagnosis, and monitoring. However, despite decades of standardization efforts, significant inter-assay variability persists, with important consequences for clinical interpretation and decision-making.ObjectiveThis review aims to evaluate the impact of PSA calibration and harmonization on reference intervals, clinical thresholds, and population-based screening strategies in contemporary clinical practice.MethodsA literature-based analysis was conducted, examining studies on PSA assay standardization, analytical variability, and evidence from population screening trials, including considerations from a Health Technology Assessment perspective.ResultsThe introduction of the World Health Organization (WHO) International Standard 96/670 improved comparability among PSA assays, yet clinically relevant differences between platforms remain. This variability is driven by differences in calibration, antibody specificity, epitope recognition, and assay design. As a result, PSA values are not directly interchangeable across assays, and assay-specific cut-offs may be necessary to maintain diagnostic performance. Historically established thresholds, such as the 4 μg/L cut-off and the \"gray zone,\" were derived using specific assay systems and are influenced by methodological limitations. PSA-derived metrics, including PSA density, improve specificity but are still affected by inter-assay variability. Evidence from large randomized trials supports a PSA cut-off of 3.0 μg/L for population screening, showing a reduction in prostate cancer mortality when implemented within structured programs; however, this threshold is intrinsically linked to the analytical characteristics of the assays used. PSA also shows relevant intra-individual biological variability beyond analytical variation, with within-subject variation of 6-13%.ConclusionsPSA standardization remains incomplete, and inter-assay variability and biological variability continues to influence clinical interpretation. The implementation of PSA-based screening programs must explicitly consider the assay-specific nature of evidence-derived thresholds, including the 3.0 μg/L cut-off, to ensure consistent, effective, and safe clinical decision-making.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"48 ","pages":"14230380261466593"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumour markers and evidence-based pathology.","authors":"Kateryna Maslova, Magdalena Chechlinska, Irmina Maria Michalek, Lukasz Taraszkiewicz, Paulina Kober, Inga Trulson, Karolina Worf, Sophie Gabriel, Laura Knoblauch, Fiona Campbell, Ian A Cree, Stefan Holdenrieder, Magdalena Kowalewska","doi":"10.1177/14230380251410478","DOIUrl":"10.1177/14230380251410478","url":null,"abstract":"<p><p>BackgroundTumour biomarkers have become increasingly important in oncology, shaping cancer diagnostics, classification, and patient management. Despite their potential, the use of cancer biomarkers in clinical settings remains limited.ObjectiveThis paper aims to outline biomarker development, from classical, serum protein markers to emerging tumour biomarkers, including meta-biomarkers, to show their diversity and point out the challenges in their development, reporting, and implementation in clinical practice as well as their relevance in evidence-based pathology and cancer classification.MethodsA literature-based analysis, incorporating insights from our ongoing research, is presented.ResultsAlthough numerous potential biomarkers, biomarker signatures, and meta-biomarkers, are being discovered, existing innovations are often not supported by sufficiently rigorous research methodologies and standardised reporting practices to enable their translation into clinical practice.ConclusionsTo ensure that biomarker discoveries are both scientifically sound and clinically useful, improved research and validation methods, along with adherence to established reporting standards, are essential. We propose the use of the Hierarchy of Evidence for Tumour Pathology as a framework to evaluate and map existing evidence and identify knowledge gaps and research priorities.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"48 ","pages":"14230380251410478"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digitoxin as a novel synergistic partner of cisplatin in triple-negative breast cancer (TNBC) cells.","authors":"Sara A Al-Shun, Magdy M Youssef, Farid A Badria","doi":"10.1177/14230380261461490","DOIUrl":"10.1177/14230380261461490","url":null,"abstract":"<p><p>BackgroundTriple-negative breast cancer (TNBC) remains clinically challenging due to its aggressive nature, high recurrence rate, and lack of targeted therapies. To address these limitations, combination chemotherapies that synergistically enhance antitumor efficacy while permitting dose reduction and supporting dose-sparing strategies are urgently needed. Cisplatin has a broad spectrum of anticancer activity. However, its resistance and dose-limiting toxicities constrain clinical benefit. Digitoxin is a cardiac glycoside that has anticancer activity.ObjectiveWe aimed to assess the nature of interaction between digitoxin and cisplatin in TNBC cells, define the most synergistic area (MSA), and estimate dose-sparing potential.MethodsWe profiled digitoxin-cisplatin effects in MDA-MB-231 TNBC cell line by checkerboard and fixed-ratio designs, quantifying interaction with Chou-Talalay combination index/dose-reduction index by CompuSyn, and multiple matrix models by SynergyFinder.ResultsThe CI analysis demonstrated synergy across all tested ratios, with the strongest synergistic interaction at a digitoxin/cisplatin ratio of 1:200 (CI = 0.30 at ED₉₇). Dose-reduction analysis showed up to 27-fold cisplatin sparing (ratio 1:25, ED₉₇). Matrix-based models confirmed synergy (Bliss 6.9, Loewe 18.6, ZIP 7.1, and HSA 14), converging on MSA at 31.25 nM digitoxin and 6.25 µM cisplatin.ConclusionOur results highlight a robust synergistic interaction between digitoxin and cisplatin in MDA-MB-231 cells with a dosing window that maximizes cytotoxic effect while potentially reducing cisplatin exposure.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"48 ","pages":"14230380261461490"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: \"LncRNA GAS5 suppresses the tumorigenesis of cervical cancer by downregulating miR-196a and miR-205\".","authors":"","doi":"10.1177/14230380251408221","DOIUrl":"https://doi.org/10.1177/14230380251408221","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"48 ","pages":"14230380251408221"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147989305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"External validation of a serum tumor marker algorithm for early prediction of no durable benefit to immunotherapy in metastastic non-small cell lung carcinoma.","authors":"Milou M F Schuurbiers, Freek A van Delft, Hendrik Koffijberg, Maarten J IJzerman, Kim Monkhorst, Marjolijn J L Ligtenberg, Daan van den Broek, Huub H van Rossum, Michel M van den Heuvel","doi":"10.1177/14230380251316788","DOIUrl":"10.1177/14230380251316788","url":null,"abstract":"<p><p>BackgroundImmune checkpoint inhibitors (ICIs) provide a significant survival benefit in non-small cell lung cancer (NSCLC) patients; however, accurately predicting which patients will benefit remains a challenge. As previously shown, the STOP model, a machine learning model based on serum tumor markers, is capable of identifying non-responders after 6 weeks of ICIs.ObjectiveThis study aims to externally validate this model and to assess the predictive value in combination with radiological response assessment using RECIST criteria.MethodsIn a cohort of 242 metastatic NSCLC patients, CYFRA, CEA, and NSE were measured before start and after 6 weeks of ICI treatment. The ability of the STOP model to predict no durable benefit (NDB; progressive disease, death within 6 months or disease control of less than 6 months) was assessed using specificity and positive predictive value (PPV). Moreover, a combination of the STOP model with RECIST after 6-8 weeks of ICIs was investigated.ResultsThe STOP model achieved a specificity of 96% (95% CI 95%-97%) and a PPV of predicting NDB of 88.1% (95% CI 85.9%-90.3%). Combining the STOP model with RECIST improved specificity and PPV to 100% and predicted NDB on average 11.6 weeks (IQR 1.8-18.0 weeks) prior to developing radiologically defined progression.ConclusionsAfter 6 weeks of ICIs, the blood-based STOP model was capable of accurately predicting NDB in metastatic NSCLC patients, earlier than conventional radiological assessment. The combined serological and radiological response assessment creates an early opportunity to safely stop ICI treatment in patients who will not benefit, although the clinical utility of the assay is limited since the high specificity comes at the cost of a lower sensitivity.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"47 ","pages":"14230380251316788"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrated bioinformatics and multi-omics investigation of the sirtuin family to identify their prognostic importance in human cancers.","authors":"Md Shahedur Rahman, Rizone Al Hasib, Md Rezanur Rahman, Polash Kumar Biswas, Abu Reza, Munzura Khatun, Mohammad Abu Hena Mostofa Jamal","doi":"10.1177/14230380251410470","DOIUrl":"https://doi.org/10.1177/14230380251410470","url":null,"abstract":"<p><p>BackgroundIn recent years, the significance of sirtuins in cancer biology has become increasingly evident, but their molecular mechanisms and prognostic impacts remain elusive.ObjectiveThe present study aimed to investigate the differential expression of the sirtuin gene family across cancers and to evaluate their prognostic value.MethodsWe used various bioinformatics databases and methodologies, including Oncomine, GEPIA, OncoDB, cBioPortal, R2 Kaplan-Meier Scanner, STRING, etc., to determine the expression pattern of the sirtuin family genes, along with their mutations and prognostic values in human cancers.ResultsIn the current study, <i>SIRT1</i>, <i>SIRT2</i>, <i>SIRT4</i>, and <i>SIRT5</i> were downregulated in lymphoma, whereas <i>SIRT6</i> and <i>SIRT7</i> were overexpressed. In breast cancer, <i>SIRT3</i>, <i>SIRT5</i>, and <i>SIRT7</i> were overexpressed, and in terms of kidney cancer, higher expression of <i>SIRT2</i>, <i>SIRT3</i>, and <i>SIRT5</i> was observed. In contrast, for leukemia, bladder, and brain cancers, most sirtuin family members showed reduced expression. We found that most mutations occurred in uterine cancer, chRCC (chromophobe renal cell carcinoma), DLBCL (diffuse large B-cell lymphoma), melanoma, pRCC (papillary renal cell carcinoma), and esophageal cancer. Moreover, we identified the relevant functional proteins through protein-protein interaction analysis to evaluate copy number alterations (CNAs) in sirtuins. The most frequent alterations were amplifications and deep deletions. Survival analysis demonstrated that <i>SIRT1</i> and <i>SIRT2</i> overexpression correlated with improved overall survival in low-grade glioma but predicted poorer outcomes in ovarian cancer. Downregulation of <i>SIRT1</i>, <i>SIRT3</i>, and <i>SIRT5</i> was associated with better prognosis in DLBCL, while <i>SIRT3</i> and <i>SIRT4</i> upregulation predicted favorable survival in testicular germ cell tumors. <i>SIRT6</i> overexpression was linked to favorable prognosis in esophageal carcinoma and sarcoma, while unfavorable outcomes were observed in hepatocellular carcinoma and cholangiocarcinoma. <i>SIRT7</i> upregulation was significantly associated with reduced survival in esophageal, liver, and uterine cancers, but surprisingly correlated with improved outcomes in urothelial carcinoma and cervical squamous cell carcinoma.ConclusionsTogether, this multi-omics analysis reveals the correlation and prognostic values of sirtuins across multiple types of human cancers and suggests that sirtuins may serve as promising biomarkers for different cancers.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"47 ","pages":"14230380251410470"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteopontin-c gene expression and subcellular localization in ovarian cancer cells: Implications for prognosis and therapeutic responses.","authors":"Mariana Concentino Menezes Brum, Annie Cristhine Moraes Sousa Squiavinato, Luciana da Torre Carneiro, Luciana Bueno Ferreira, Alessandra Serain, Mariana Boroni, G Nestal de Moraes, Erp Gimba","doi":"10.1177/14230380251375818","DOIUrl":"https://doi.org/10.1177/14230380251375818","url":null,"abstract":"<p><p>BackgroundOsteopontin is a glycophosphoprotein aberrantly expressed in several tumor types, which exhibits several isoforms generated by post-translational and post-transcriptional mechanisms, including alternative splicing. Among total osteopontin (tOPN), the osteopontin-c (OPN-c) splice variant has been the most explored with an oncogenic role described for a range of tumor types. Especially in ovarian cancer (OC) cells, OPN-c is found overexpressed, presenting both diagnostic and prognostic implications.ObjectiveIn this review article, we aim to outline OPN-c roles in cancer, particularly in OC, in which it has been reported as a diagnostic biomarker.MethodsWe used PubMed search, and experimental procedures were summarized at the Figure legends.ResultsWe identified cytoplasmic, perinuclear, and nuclear OPN-c in OC cells that overexpress this OPN splice variant. Moreover, we report that OPN-c splicing isoform is found highly expressed in endometrioid OC patients' samples, compared to non-neoplastic ovarian tissues. Also, OPN-c expression levels have been associated with worse overall survival and worse progression-free survival in patients with both endometrioid and serous OC. Furthermore, OPN-c may be involved in a wide range of tumor features evoked by signaling pathways, such as AKT, ERK, and FAK.ConclusionsTherefore, a better comprehension of OPN-c roles in OC can further contribute to its application as a biomarker as well as a target for putative treatment strategies, especially those aiming to sensitize tumor cells to chemotherapeutic agents currently used in the OC treatment.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"47 ","pages":"14230380251375818"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of concern: \"Prognostic value of preoperative peripheral monocyte count in patients with hepatocellular carcinoma after liver transplantation\".","authors":"","doi":"10.1177/14230380251411266","DOIUrl":"https://doi.org/10.1177/14230380251411266","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"47 ","pages":"14230380251411266"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}