Clinical & Translational Oncology[JOURNAL]
Sun
200 papers
Exploration of precise classification and therapeutic targets of breast cancer based on genes related to neuro-cancer crosstalk.
Li Z, Sun C, Cui Y … +4 more , Huang Y, Liu M, Xie H, Wang S
Transl Oncol · 2026 Feb · PMID 41406890 · Full text
This investigation examines neural-cancer crosstalk in breast cancer, utilizing TCGA/GEO transcriptomic and single-cell data to develop a neural-cancer crosstalk prognostic signature and evaluate its clinical relevance....
This investigation examines neural-cancer crosstalk in breast cancer, utilizing TCGA/GEO transcriptomic and single-cell data to develop a neural-cancer crosstalk prognostic signature and evaluate its clinical relevance. We identified four core genes-L1CAM, TACR1, GFRA1, and NTRK3-using univariate Cox regression and LASSO-Cox regression to develop a risk scoring model. The prognostic signature showed consistent predictive accuracy across validation cohorts, with high-risk patients demonstrating markedly reduced survival. Multivariate analysis established the risk score as an independent prognostic indicator. Immune profiling identified an immunosuppressive phenotype in high-risk cases, featuring elevated Treg infiltration and impaired antigen presentation. Genomic analysis revealed significantly higher TP53 mutation frequency in high-risk versus low-risk patients. Drug sensitivity predictions indicated that the high-risk group exhibited increased sensitivity to targeted therapies such as Lapatinib, but enhanced resistance to conventional chemotherapy. Single-cell sequencing revealed the heterogeneity of breast cancer cells and elucidated a neuro-immune-tumor interaction network dominated by MIF and MDK signaling pathways. Functional validation studies demonstrated that L1CAM knockdown effectively suppressed malignant phenotypes in breast cancer cells, including proliferation, migration, and invasive capacity in vitro. This study provides new insights into the regulatory mechanisms of the neural microenvironment in breast cancer, and the established prognostic model and identified potential therapeutic targets hold significant clinical implications for personalized treatment.
Radiomics as a visual tool with potential clinical implications: A comment on the implementation of habitat radiomics in a liver cancer series.
Fiz F, Ammirabile A, Viganò L
Transl Oncol · 2026 Feb · PMID 41401633 · Full text
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Circular RNA circSCMH1 regulates glycolysis to inhibit gastric cancer metastasis via miR-296-3p/HSPB7-GLUT3 axis.
Yang Y, Wang Q, Gong Z … +8 more , Chen J, Yang Y, Zhao L, Zhai Y, Zhao T, Du W, Zhang J, Guo W
Transl Oncol · 2026 Feb · PMID 41401631 · Full text
Metastasis is main reason leading to gastric cancer (GC) caused death. GC metastasis is known to be associated with complex factors, of which circular RNAs (circRNAs) become hot molecules recently. How to effectively sel...
Metastasis is main reason leading to gastric cancer (GC) caused death. GC metastasis is known to be associated with complex factors, of which circular RNAs (circRNAs) become hot molecules recently. How to effectively select key molecules participating in GC metastasis is still needing to be resolved. Through next-generation sequencing, metastasis-driven circRNAs were selected by comparing cancer and para-cancer tissues from GC patients with different metastasis tendency. The biological function of circSCMH1 was identified in vivo and in vitro. Through luciferase reporter system and functional rescue test, the downstream microRNA and target gene were identified. Glucose uptake, lactic acid production and ATP production were detected to estimate glycolysis level. Moreover, 110 GC samples were collected and following clinical association analysis was conducted. circSCMH1 showed significantly lower expression in high-metastasis GC. circSCMH1 could suppress glycolysis to inhibit GC proliferation and metastasis in vivo and in vitro, and played its biological function through miR-296-3p/HSPB7-GLUT3 axis. circSCMH1 showed closely association with GC lymph node metastasis and prognosis. circSCMH1 could inhibit gastric cancer metastasis through regulating glycolysis via miR-296-3p/HSPB7-GLUT3 axis. circSCMH1 could become potential biomarker for GC lymph node metastasis and even therapeutic target in the future.
Development and validation of a TOP2A based index clinical model for kidney renal clear cell carcinoma.
Shi X, Song B, Wang B … +8 more , Chen A, Hu J, Xie G, Huang J, Huang C, Cheng Y, Yan Z, Du W
Transl Oncol · 2026 Feb · PMID 41391381 · Full text
OBJECTIVE: TOP2A (Topoisomerase II alpha) is significantly overexpressed in kidney renal clear cell carcinoma (KIRC), and its expression level is significantly associated with accelerated tumor progression and poor progn...
OBJECTIVE: TOP2A (Topoisomerase II alpha) is significantly overexpressed in kidney renal clear cell carcinoma (KIRC), and its expression level is significantly associated with accelerated tumor progression and poor prognosis in patients. Therefore, the aim of this study is to systematically analyze the biological functions of TOP2A-related molecular markers in KIRC by constructing a TOP2A based index clinical model. Additionally, we aim to screen potential therapeutic targets to guide the optimization of clinical intervention strategies. METHODS: Integrated TCGA-KIRC data were standardized and analyzed via PCA. Differentially expressed genes between TOP2A high/low expression groups were screened and functionally annotated (GO/KEGG). WGCNA identified core TOP2A-associated modules, combined with Cox regression to construct a prognostic model. GSEA evaluated pathway activity, immune infiltration, and immune checkpoint correlations. Regulatory networks (miRNA/lncRNA/RBP), mutation profiles, and methylation-transcriptome interactions were explored. RESULTS: 5500 TOP2A-related deregulated genes were identified, with core modules enriched in cell cycle/DNA replication pathways. The TOP2A-index model inversely correlated with patient survival. High TOP2A expression scores showed positive associations with immune checkpoint genes. Multi-omics analyses revealed global regulatory networks linking TOP2A to tumor microenvironment modulation. CONCLUSION: This study developed a TOP2A based index clinical model that will aid in predicting the prognosis of KIRC patients.
Radial glial cells and glioblastoma: how developmental neurobiology can inform our understanding of brain cancer initiation, treatment resistance, and resilience.
Love CA, Figg JW, Engelbart M … +2 more , West I, Flores C
Transl Oncol · 2026 Feb · PMID 41391380 · Full text
Glioblastoma (GBM) remains one of the most lethal brain malignancies, with an abysmal five-year survival rate near 6 %. Despite advances in tumor biology, clinical outcomes have not improved, partially due to glioma stem...
Glioblastoma (GBM) remains one of the most lethal brain malignancies, with an abysmal five-year survival rate near 6 %. Despite advances in tumor biology, clinical outcomes have not improved, partially due to glioma stem cells (GSCs) that drive treatment resistance. Radial glial cells (RGCs), recognized as key progenitors in neurodevelopment, have recently gained attention in GBM research due to RGC-like populations being identified in GBM. RGCs have striking similarities with GSCs, including their mechanisms of self-renewal, pluripotency, and migration. This review highlights those parallels between as well as recent studies on their critical intersections to expand our comprehension of neurodevelopmental paradigms in GBM. Understanding these parallels may uncover developmental pathways that can be exploited to improve therapeutic strategies for GBM.
GATAD2B promotes ovarian cancer malignant progression via MYC/CD47 Axis.
Guo T, Nie D, Xu J … +4 more , Zhou R, Ye Y, Zhu Y, Lin M
Transl Oncol · 2026 Feb · PMID 41389672 · Full text
This study elucidates the biological function of GADAT2B and its underlying mechanism in ovarian cancer.The results of our experiment showed that GATAD2B highly expressed in OC tissues, which was associated with a poor p...
This study elucidates the biological function of GADAT2B and its underlying mechanism in ovarian cancer.The results of our experiment showed that GATAD2B highly expressed in OC tissues, which was associated with a poor prognosis. METTL3 regulated the expression of GATAD2B in OC cells via m6A methylation. And it was unveiled that up-regulation of GATAD2B significantly promoted OC growth, invasion, migration of and suppressed the tumor cell apoptosis. After transfected with sh-GATAD2B, the OC cells were just the reverse in behavior. Additionally, GATAD2B played a crucial role in regulating CD47 expression via the MYC-mediated pathway, and the further experiments showed that GATAD2B and MYC were co-localized on tumor cell membrane. The in vivo and in vitro experiments showed an important role of GATAD2B in OC growth and metastasis, as confirmed by the inhibited tumor growth and the enhanced M1 macrophage infiltration.GATAD2B m6A methylation mediated by METTL3 can promote malignant progress. And GATAD2B can promote immune escape by MYC/CD47 pathway in OC, providing a promising anti-OC therapeutic target.
Radiotherapy in the management of PDAC, from past to present.
Dardare J, Martz N, Witz A … +6 more , Betz M, Michel C, Gilson P, Merlin JL, Lambert A, Harle A
Transl Oncol · 2026 Jan · PMID 41365129 · Full text
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal forms of cancer, with a dismal survival rate. Therapeutic options are restricted in surgery for patients with resectable disease and in chemotherapy...
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal forms of cancer, with a dismal survival rate. Therapeutic options are restricted in surgery for patients with resectable disease and in chemotherapy for those with unresectable disease. The potential benefits of radiotherapy (RT) or chemoradiotherapy (CRT) have been extensively investigated in both neoadjuvant and adjuvant settings in the management of patients with PDAC. Nevertheless, a substantial number of clinical trials have yielded conflicting findings, thereby rendering the impact of RT on patient survival and margin-negative (R0) resection inconclusive. A comprehensive examination of the historical evolution of RT in PDAC, encompassing the identification of both constraints and opportunities for advancement, is essential to establish RT as a promising therapeutic avenue for patients with PDAC. The aim of this review is to provide a synthesis of past clinical trials and future studies to elucidate the evolving role of RT in the management of PDAC as adjuvant and neoadjuvant CRT across different stages of the disease.
Phenazine 5,10-dioxide analogues as potential therapeutics in AML: Efficacy on patient-derived blasts, in zebrafish larvae xenografts and synergy with venetoclax.
Reiten IN, Aesoy R, Førde JL … +6 more , Khose GM, Viktorsson EÖ, Bruserud Ø, Rongved P, Reikvam H, Herfindal L
Transl Oncol · 2026 Jan · PMID 41353995 · Full text
Although several new therapies against acute myeloid leukaemia (AML) have emerged the past years, patients who are ineligible for intensive chemotherapy are still treated with less effective treatments to minimise therap...
Although several new therapies against acute myeloid leukaemia (AML) have emerged the past years, patients who are ineligible for intensive chemotherapy are still treated with less effective treatments to minimise therapy-associated mortality. Several phenazine 5,10-dioxide derivates have previously demonstrated to selectively induce apoptosis in human AML cells. In the present work, we have continued investigations on phenazine 5,10-dioxides to reveal their therapeutic potential in AML using in vitro and in vivo experiments. From a panel of primary AML blasts from 61 non-selected patients, 58 showed high or intermediate response to treatment with the phenazine 5,10-dioxides. This included blasts with biological characteristics associated with poor prognosis, such as FLT3 internal tandem duplication, NPM-1 wild type, CD34, and adverse cytogenetics. The phenazine 5,10-dioxides cytotoxicity towards primary blasts correlated with the blast's sensitivity to daunorubicin, presumably due to similar mode of action towards AML cells. Three phenazine 5,10-dioxides had low toxicity in zebrafish larvae, and from these, two were found effective towards zebrafish larvae AML xenografts. Additionally, synergism with the AML drug venetoclax (VTX) was found in the AML cell lines MOLM-13 and MV4-11. The efficacy of phenazine 5,10-dioxides towards primary AML blasts, synergism with VTX and low toxicity in effective concentrations in zebrafish larva AML xenografts suggests potential for these compounds in future AML therapy for patients unfit for intensive chemotherapy.
Shaping the future one slice at a time: How 3D organotypic tumour slice models are driving drug discovery in ovarian cancer.
Edwards M, Caruana P, Escar M … +1 more , Céspedes MV
Transl Oncol · 2026 Jan · PMID 41351993 · Full text
Despite therapeutic advancements, ovarian cancer remains one of the most lethal gynaecological malignancies, highlighting the urgent need for innovative drug discovery approaches. Traditional 2D cell line models fail to...
Despite therapeutic advancements, ovarian cancer remains one of the most lethal gynaecological malignancies, highlighting the urgent need for innovative drug discovery approaches. Traditional 2D cell line models fail to accurately replicate the complexity of the tumour and its microenvironment (TME), leading to suboptimal drug evaluations. Organotypic tumour slice culture (OTSC) has emerged as a promising 3D ex vivo platform that preserves native tissue architecture, cellular interactions, and molecular heterogeneity of the tumour and its TME, providing a more physiologically relevant system for drug testing. This review examines the evolution of OTSC in ovarian cancer and its applications across chemotherapy, targeted therapy, immunotherapy, and virotherapy. We highlight the role of OTSC in identifying predictive biomarkers of drug response, drug resistance mechanisms - including those in the stroma - and elucidating novel therapeutic strategies. While OTSC has demonstrated its ability to rapidly provide insights into patient-specific responses, further integration of advanced multi-omics analyses could enhance its potential as a precision medicine platform. With its 3D heterogenic complexity, OTSC could also facilitate the development and evaluation of TME-directed therapies, novel multitarget drugs, and tumour-targeting drug delivery systems, ultimately shaping the future of ovarian cancer therapy and improving clinical outcomes.
piR-43452 suppresses bladder cancer progression and enhances gemcitabine sensitivity via GTSF1/PIWIL4-mediated LRP1 mRNA destabilization.
Shi Y, Sun J, Yu K … +11 more , Lu D, Niu X, Li Y, Huang S, Luo J, Wang X, Ma X, Li J, Ying Y, Xie L, Liu B
Transl Oncol · 2026 Jan · PMID 41344056 · Full text
Piwi-interacting RNAs (piRNAs), while crucial for genomic integrity in germline cells, remain poorly characterized in somatic cancers. This study identifies piR-43452 as a significantly downregulated piRNA in bladder can...
Piwi-interacting RNAs (piRNAs), while crucial for genomic integrity in germline cells, remain poorly characterized in somatic cancers. This study identifies piR-43452 as a significantly downregulated piRNA in bladder cancer (BCa), with loss of expression correlating clinically with muscle invasion and lymph node metastasis. Through assays in vitro and in vivo, we demonstrate that piR-43452 acts as a potent tumor suppressor, inhibiting BCa cell proliferation, migration, and xenograft growth while promoting apoptosis. Mechanistically, we identified that piR-43452 directly binds the 3'UTR of LRP1 mRNA and recruits the GTSF1/PIWIL4 complex, which enhances target cleavage through GTSF1-dependent conformational activation. This post-transcriptional regulation led to significant LRP1 suppression, subsequently inhibiting proliferation and restoring chemosensitivity. Our findings establish a novel piRNA-guided mechanism for overcoming chemoresistance and suggest that targeting the piR-43452/GTSF1/PIWIL4/LRP1 axis may provide therapeutic benefit in gemcitabine-resistant BCa.
Biomarker analysis from a Phase 1/1b study of tusamitamab ravtansine in patients with advanced non-small cell lung cancer.
Gazzah A, Ternès N, Lee JS … +13 more , Wang E, Carene D, Wang H, Masson N, Boitier E, Lartigau A, Mace N, Chadjaa M, Dib C, Nunes M, Muzard G, Longuemaux-Valence S, Bauchet AL
Transl Oncol · 2026 Jan · PMID 41337813 · Full text
BACKGROUND: Tusamitamab ravtansine demonstrated antitumor activity in the Phase 1/1b study of advanced non-squamous non-small cell lung cancer with high (HE, ≥2+ intensity in ≥50 % of tumor cells) or moderate (ME, ≥2+ in...
BACKGROUND: Tusamitamab ravtansine demonstrated antitumor activity in the Phase 1/1b study of advanced non-squamous non-small cell lung cancer with high (HE, ≥2+ intensity in ≥50 % of tumor cells) or moderate (ME, ≥2+ intensity in ≥1 % to <50 % of tumor cells) carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression. Tumor CEACAM5 expression, biomarker associations and whether biomarkers predict objective response rate (ORR) were explored. METHODS: We assessed CEACAM5, circulating CEACAM5 (cCEACAM5) and CEA (cCEA). Enrollment was according to immunohistochemistry (IHC) CEACAM5 membrane expression: HE (n=64) and ME (n=28). Patients received tusamitamab ravtansine 100 mg/m intravenously every 2 weeks. RESULTS: cCEA and cCEACAM5 were strongly associated (Spearman ρ, 0.99), with moderate associations between IHC CEACAM5 and cCEA or cCEACAM5 (Spearman ρ, 0.43 and 0.38). In patients with baseline cCEA data, 40.3 % (25/62) of HE and 25 % (7/28) of ME had cCEA ≥100 µg/L (median: 71.6 µg/L [1-8809] versus 12.4 µg/L [0.5-684]). Among response-evaluable patients in HE, ORR for high cCEA (≥100 µg/L) was 41.7 % (10/24) versus 8.1 % (3/37) for low cCEA, and in ME, ORR was 0/7 versus 10 % (2/20). Elevated CEACAM5 mRNA was observed in HE versus ME (P = 0.0027). EGFR and KRAS alterations were present in 44.8 % and 65.5 % of HE and in 21.4 % and 78.6 % of ME patients, respectively. CONCLUSIONS: In CEACAM5 HE, the ORR was greater with high versus low cCEA. Associations were observed between cCEA and cCEACAM5; IHC CEACAM5, cCEA, and cCEACAM5; IHC CEACAM5 and CEACAM5 mRNA, but not between IHC CEACAM5 and oncogenic drivers. CLINICAL TRIAL REGISTRATION: NCT02187848.
Prediction of local recurrence in cohorts of head and neck cancer patients after intensity-modulated radiation therapy based on CT radiomics: A double-center observation study.
Xu J, Liu Q, Yin Y … +2 more , Gao J, Dong G
Transl Oncol · 2026 Jan · PMID 41337812 · Full text
OBJECTIVE: This study aims to develop and validate a CT-based radiomics model for predicting the prognosis of head and neck cancer patients, particularly those with nasopharyngeal carcinoma (NPC), following intensity-mod...
OBJECTIVE: This study aims to develop and validate a CT-based radiomics model for predicting the prognosis of head and neck cancer patients, particularly those with nasopharyngeal carcinoma (NPC), following intensity-modulated radiation therapy (IMRT). METHODS: We conducted a retrospective analysis involving 392 pathologically confirmed NPC patients from two centers. Center A contributed 226 patients to the training cohort, while Center B provided 64 patients for the validation cohort. Features extracted from CT images were utilized to develop two predictive models: a clinically combined radiomics model and a standalone radiomics model. Dimensionality reduction and nested cross-validation were employed in the model development process. The performance of the models was assessed and validated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA), with differences between the models evaluated using the DeLong test. RESULTS: Our findings indicate that the clinically combined radiomics model outperforms the standalone radiomics model in prognostic prediction. The area under the curve (AUC) for the combined model was 0.90 in the training cohort, while the validation cohort achieved an AUC of 0.86. DCA further confirmed that the performance of all models exceeded that of blindly predicting patient outcomes as either all negative or all positive. Subsequent comparisons using the DeLong test revealed significant differences in predictive performance between the standalone radiomics model and the clinically combined radiomics model, with P-values <0.05. CONCLUSION: The clinically combined radiomics model demonstrates promising performance in predicting the prognosis of NPC patients following IMRT.
Circular RNA circAHSA1 serves as a stable serum biomarker for the diagnosis and progression of gastric cancer.
He J, Ma S, Kuai S … +1 more , Ju S
Transl Oncol · 2026 Jan · PMID 41330006 · Full text
BACKGROUND: Gastric cancer (GC) remains a major cause of cancer-related mortality globally, largely due to the absence of reliable non-invasive biomarkers for early detection. Circular RNAs (circRNAs), characterized by c...
BACKGROUND: Gastric cancer (GC) remains a major cause of cancer-related mortality globally, largely due to the absence of reliable non-invasive biomarkers for early detection. Circular RNAs (circRNAs), characterized by covalently closed-loop structures, stability, and detectability in circulation, have emerged as promising liquid biopsy candidates. METHODS: circAHSA1 (hsa_circ_0032777) was identified through GEO dataset screening (GSE121445) and validated in GC tissues, serum, and cell lines using qRT-PCR with optimized internal reference selection. Diagnostic performance was assessed using ROC analysis and DeLong tests, evaluating circAHSA1 alone and in combination with CEA, CA199, and CA724. Biological functions were examined through proliferation, apoptosis, migration, and invasion assays. Subcellular localization and potential downstream miRNA interactions were analyzed using nuclear-cytoplasmic fractionation and multi-database bioinformatic prediction. RESULTS: circAHSA1 expression was significantly elevated in GC tissues, serum, and cell lines, and correlated with lymph node metastasis, differentiation status, and TNM stage. Serum circAHSA1 effectively discriminated GC from healthy controls (AUC = 0.787) and gastritis patients (AUC = 0.752), outperforming conventional markers, with statistical superiority confirmed by DeLong analysis. Combined detection further improved diagnostic accuracy (AUC = 0.871). Functionally, silencing circAHSA1 suppressed GC cell proliferation, migration, and invasion while enhancing apoptosis and inducing cell-cycle arrest. Bioinformatic analysis suggested miR-647 and miR-661 as potential downstream targets. CONCLUSIONS: circAHSA1 is a stable, GC-specific circulating biomarker with both diagnostic and functional relevance. These findings support circAHSA1 as a promising candidate for liquid biopsy-based GC detection and a potential therapeutic target.
The prognostic value of tumor macroscopic morphology in colorectal cancer.
Lin H, Zhao Z, Ma Y … +5 more , Shi X, Guo L, Wang J, Fu W, Zhou X
Transl Oncol · 2026 Jan · PMID 41319390 · Full text
BACKGROUND: This study aims to evaluate the prognostic value of tumor macroscopic morphology in colorectal cancer (CRC) and understand the molecular mechanism behind different tumor morphologies. METHODS: 642 eligible pa...
BACKGROUND: This study aims to evaluate the prognostic value of tumor macroscopic morphology in colorectal cancer (CRC) and understand the molecular mechanism behind different tumor morphologies. METHODS: 642 eligible patients were enrolled in this study, including 335 patients in the prospective study and 307 patients in the retrospective study. CRCs were categorized into protruded, ulcerative, and infiltrative types according to our morphological classification, and their clinicopathological features and prognosis were analyzed. Furthermore, bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq) and immunohistochemistry were performed to map the tumor microenvironment of different tumor morphologies. RESULTS: In the prospective cohort, CRC with infiltrative type were significantly associated with unfavorable clinicopathological characteristics and poor survival compared with ulcerative type and protruded type. Bulk RNA sequencing revealed that the infiltrative type correlated with higher expression of fibroblast activation protein-α (FAP), periostin and platelet endothelial cell adhesion molecule-1 (PECAM-1), which corresponded with elevated cell proportions of stromal cells and endothelial cells in scRNA-seq. Additionally, a retrospective cohort was conducted to assess the value of preoperative endoscopic morphology and radiological morphology, both independently associated with disease-free survival (DFS). CONCLUSION: We proposed a revised tumor macroscopic morphology classification system in CRC. The infiltrative type is associated with poorer clinical outcomes, characterized by increased cancer-associated fibroblast (CAF) infiltration and enhanced angiogenesis compared with other types. Importantly, when expanded to endoscopy and CT preoperatively, both endoscopic and radiological morphology can serve as preoperative predictors of DFS.
Evaluation of the 1021-HRD assay compared to established HRD testing platforms in ovarian cancer.
Papadopoulou E, Fountzilas E, Metaxa-Mariatou V … +18 more , Tsantikidi A, Tsaousis G, Meintani A, Florou-Chatzigiannidou C, Maxouri S, Papazisis K, Floros T, Papadimitriou C, Timotheadou E, Papadopoulou K, Papathanasiou A, Grigoriadis D, Fu X, Zheng X, Xing Y, Du X, Truican A, Nasioulas G
Transl Oncol · 2026 Jan · PMID 41319389 · Full text
PARP inhibitors have revolutionized ovarian cancer treatment, with benefits strongly linked to the presence of Homologous Recombination Deficiency (HRD). Although HRD testing was originally conducted on centralized platf...
PARP inhibitors have revolutionized ovarian cancer treatment, with benefits strongly linked to the presence of Homologous Recombination Deficiency (HRD). Although HRD testing was originally conducted on centralized platforms, there is growing demand for scalable, accessible, and robust solutions capable of supporting expanded clinical utilization. In the present study, a decentralized NGS-based assay was compared for its ability to effectively identify HRD positive patients when compared to the reference assay as well as other testing platforms. Eighty-two cases of ovarian cancer patients previously tested using the reference HRD assay (Myriad MyChoice® CDx assay) were evaluated by an NGS based HRD assay, the 1021-HRD assay (GenePlus), that provides genomic instability (GI) analysis along with tumor molecular profiling. HRD status, GI status (referred to as HRD-score), and even BRCA1/2 mutation detection were assessed for concordance with the reference test and the analytical accuracy of the assay was calculated. Additionally, GI alignment across alternative HRD testing platforms was examined. Finally, the association between key tumor alterations and the HRD status was evaluated. The 1021-HRD assay demonstrated an overall HRD classification agreement of approximately 92.68 % (κ = 0.841) in comparison to the reference method, as evidenced by the results, with 81.25 % specificity and 100 % sensitivity. These features generally suggest consistent performance, with only minor discrepancies observed. The BRCA1/2 alterations detected were 97.56 % in agreement with the approved assay. The Pearson r value of 0.878 indicates a strong correlation between the GI values obtained. The assay's capacity to detect non-BRCA1/2 HRD phenotypes was verified by the observation that 55.56 % of BRCA-wildtype malignancies were HRD-positive. Of particular interest, combining molecular profiling with GI analysis, the assay identified additional actionable alterations in 65 % of the cases, revealing clinically relevant biomarkers beyond the homologous recombination pathway. This wide-ranging approach may provide more diagnostic and therapeutic insight than HRD testing alone. In conclusion, the 1021-HRD assay is a dependable, decentralized alternative for HRD testing. It can provide a more comprehensive genomic characterization and exhibits remarkable analytical concordance with current standards. Its combined format and accessibility render it well-suited for real-world use in personalized ovarian cancer care. Its additional capacity to reveal more extensive tumor genomic alterations improves clinical decision-making and underscores the importance of integrating HRD scoring with comprehensive molecular profiling in personalized oncology.
Clinical and molecular variations in Burkitt lymphoma.
O'Connor E, Scanlan P, Smith OP … +1 more , Halasz M
Transl Oncol · 2026 Jan · PMID 41297313 · Full text
Burkitt lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma, historically classified into three subtypes; endemic, sporadic and immunodeficiency associated BL. Accumulating evidence suggests that Epstein-Barr viru...
Burkitt lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma, historically classified into three subtypes; endemic, sporadic and immunodeficiency associated BL. Accumulating evidence suggests that Epstein-Barr virus (EBV)-positive and EBV-negative BL represent biologically distinct entities. In this review, we aim to compare the clinicopathological and molecular differences in BL in the context of EBV status and chronic malaria infection. From our review, clinical features of BL vary by both EBV status and geographical region, reflecting underlying epidemiological differences. The cell of origin may also differ between EBV-positive and EBV-negative cases. At a molecular level, differences based on EBV status include variations in the immunoglobulin (IG)::MYC translocation breakpoints, mutations in the inhibitor of DNA binding 3 (ID3)/ transcription factor 3 (TCF3)/ cyclin D3 (CCND3) signalling axis, the anti-apoptotic effects of EBV latency gene products, differences in the alternative reading frame (ARF)/ mouse double minute 2 (MDM2)/p53 and ataxia-telangiectasia mutated (ATM)/ ATM and RAD3-related (ATR) pathways, and deregulation of B-cell leukemia/lymphoma 2 (BCL-2) family proteins. We further discuss the theory that aberrant activation-induced cytidine deaminase (AID) expression, in the setting of EBV infection and chronic malaria exposure, is the most likely aetiology of endemic BL. This review provides a comprehensive summary of key molecular differences between EBV-positive and EBV-negative BL, that may guide the development of future targeted therapeutic strategies.
Apolipoprotein C1 functions as a target of thyroid carcinoma and synergistic effects with promising candidate-cyclopamine.
Wang R, Wang B, Shi J … +2 more , Zhu Z, Yao Z
Transl Oncol · 2026 Jan · PMID 41289702 · Full text
There is an urgent need to identify novel therapeutic targets for papillary thyroid carcinoma (PTC). APOC1 (Apolipoprotein C1) has emerged as a candidate: it is overexpressed in several cancers and its high expression of...
There is an urgent need to identify novel therapeutic targets for papillary thyroid carcinoma (PTC). APOC1 (Apolipoprotein C1) has emerged as a candidate: it is overexpressed in several cancers and its high expression often associates with worse clinical outcomes. Using bioinformatic analysis of TCGA-THCA RNA-seq data, we found that APOC1 is highly expressed in PTC and that elevated APOC1 correlates with poorer patient prognosis and with signatures of immune-evasion. We validated these observations in PTC cell lines. Immunofluorescence, colony-formation assays, CCK-8 proliferation measurements, and flow-cytometry apoptosis analysis all indicate that APOC1 promotes proliferation, enhances colony survival, and confers resistance to apoptosis. To identify candidate therapeutics that target APOC1-related pathways, we queried the Connectivity Map using shared differentially expressed genes (DEGs) and nominated cyclopamine as the top small-molecule hit. Cyclopamine reduces PTC cell proliferation and induces apoptosis in vitro; APOC1 depletion further sensitizes cells to cyclopamine, producing greater inhibition of proliferation and increased cell death. Finally, cyclopamine suppresses tumor growth in a PTC mouse model. Together, these results implicate APOC1 as a driver of PTC progression and immune evasion and identify cyclopamine as a promising therapeutic that acts, at least in part, through APOC1-related signaling. Our study thus provides a rationale for targeting APOC1 as a novel treatment strategy for papillary thyroid carcinoma.
Multi-omics analysis reveals the heterogeneity and interactions among stromal and tumor cells in gastric cancer.
Yang C, Jin Y, Zhao X … +4 more , Zhou L, Xu X, Zhan Q, Zhang Q
Transl Oncol · 2026 Jan · PMID 41275708 · Full text
OBJECTIVE: This study aims to investigate the heterogeneity of cancer-associated fibroblasts (CAFs) and smooth muscle cells (SMCs) and their interactions with malignant epithelium in gastric cancer (GC), with the goal of...
OBJECTIVE: This study aims to investigate the heterogeneity of cancer-associated fibroblasts (CAFs) and smooth muscle cells (SMCs) and their interactions with malignant epithelium in gastric cancer (GC), with the goal of identifying potential therapeutic targets. METHODS: We performed a multi-omics analysis integrating single-cell RNA sequencing and spatial transcriptomics, complemented by trajectory inference, regulon activity mapping, ligand-receptor interaction modeling, and survival association in external cohorts. RESULTS: Two malignant epithelial programs emerged-Tumor Cell 1 (TC 1) (wound-healing/proliferative) and Tumor Cell 1 (TC 2) (highly cycling/metabolic). In TCGA-STAD (The Cancer Genome Atlas - Stomach Adenocarcinoma), high TC 1 scores associated with worse overall survival (P < 0.01), whereas TC 2 showed a nonsignificant trend. The stroma comprised nine populations; tumors were enriched for RGS5⁺ SMCs and FAP⁺ fibroblasts, with depletion of homeostatic PI16⁺ fibroblasts. Pseudotime traced a PI16⁺→CCL11⁺→PDGFRA⁺→FAP⁺ continuum featuring late NF-κB/STAT activation and extracellular matrix (ECM)-remodeling; SMCs rewired from contractile MYH11⁺ to angiocrine RGS5⁺ states. Ligand-receptor analysis indicated asymmetric tumor-stroma crosstalk: TC 1 preferentially engaged vaso-regulatory/EGFR-immune signaling to activate CAFs and SMCs, while TC 2 amplified PDGF/MDK growth-factor circuits; stromal feedback via WNT/NRG/HGF/TGF-β reinforced malignant programs. Spatial maps confirmed EPCAM-high tumor nests encased by COL1A2/FAP⁺ fibroblastic shells interwoven with ACTA2/RGS5⁺ strands. CONCLUSION: This study highlights the critical role of CAFs and SMCs heterogeneity and their interactions within the GC TME (Tumor microenvironment). Targeting stromal pathways such as PDGF, TGF-β, and NF-κB signaling, immunomodulating CAFs, and disrupting SMC-derived vascular niches may improve therapeutic responses. Further experimental validation of ligand-receptor pairs and spatial determinants is warranted.
B2M regulates ELANE in pyroptosis to affect pancreatic cancer progression.
Xie H, Hu X, Cai Y … +2 more , Zhu S, Deng Z
Transl Oncol · 2026 Jan · PMID 41273989 · Full text
The role of pyroptosis in pancreatic cancer remains controversial. Using two-sample Mendelian randomization (MR) integrating GWAS data from FinnGen (314,193 controls, 731 cases), pQTL data from Iceland, and the UK Bioban...
The role of pyroptosis in pancreatic cancer remains controversial. Using two-sample Mendelian randomization (MR) integrating GWAS data from FinnGen (314,193 controls, 731 cases), pQTL data from Iceland, and the UK Biobank, we systematically investigated causal links between pyroptosis genes and pancreatic cancer. We found that Beta-2-microglobulin (B2M) indirectly increases pancreatic cancer risk by upregulating Neutrophil Elastase (ELANE)-to our knowledge, this is the first study to establish a causal, mediation-based genetic link between B2M and ELANE in the context of pancreatic cancer. Mediation analysis revealed ELANE accounts for 20.572 % [15.32%-25.81 %] of this effect. Sensitivity analyses confirmed robustness without significant pleiotropy, and bioinformatics validation supported our MR findings. Drug sensitivity analysis further identified potential therapeutic agents. The findings support B2M as a diagnostic biomarker for pancreatic cancer, given its significant overexpression in tumors and high diagnostic accuracy (AUC = 0.976, 95 % CI: 0.958-0.993), and highlight the B2M-ELANE axis-identified through a data-driven MR mediation framework-as a promising therapeutic target.
Development of a single-cell derived MDSCs signature score for prognostic risk stratification and therapeutic decision guidance in breast cancer.
Yin J, Li B, Xiong H … +2 more , Gan J, Liang L
Transl Oncol · 2026 Jan · PMID 41252877 · Full text
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) function as critical immunosuppressive constituents within the breast cancer tumor microenvironment (TME). However, their molecular variability and clinical translatio...
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) function as critical immunosuppressive constituents within the breast cancer tumor microenvironment (TME). However, their molecular variability and clinical translation potential remain inadequately characterized. METHODS: By combining single-cell RNA sequencing (scRNA-seq) with bulk multi-omics datasets, we screened and confirmed MDSCs signature genes specific to breast cancer. A prognostic risk scoring model was constructed using machine learning approaches and tested across multiple independent patient cohorts. The model's predictive capacity for chemotherapy sensitivity, immunotherapy responsiveness, and TME features was systematically assessed. RESULTS: After integrating the single-cell datasets GSE161529 and GSE176078, we identified 12,767 MDSCs along with their 209 characteristic genes. To ensure the reliability of our results, we employed various analytical methods and utilized diverse data for validation. From this signature, a 5-gene risk score model comprising BCL2A1, GDI2, GRINA, RNASE1, and SERPINA1 was constructed, demonstrating robust prognostic stratification with a 1- to 10-year overall survival (OS) AUC exceeding 0.6 and independent predictive value. High-risk patients exhibited characteristic features of an immunosuppressive tumor microenvironment (TME), including increased M2 macrophages and regulatory T cells, alongside diminished cytotoxic T lymphocyte activity. These patients also showed poor responses to both chemotherapy and immunotherapy. CONCLUSION: This investigation marks the initial systematic characterization of a new MDSCs gene signature in breast cancer, alongside the establishment of an MDSCs-associated marker scoring framework with multi-aspect clinical translation capability, thereby linking MDSCs fundamental biology to precision oncology in this cancer type.
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