Frontiers in Oncology最新文献

Background: Testicular cancer (TC) is the most common malignancy in young men, with incidence increasing globally, especially in high-income countries. Although survival has improved due to advances in diagnosis and treatment, disparities in TC burden remain. This study analyzes global, regional, and national trends in TC incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021, and projects future trends to 2035.

Methods: Data were obtained from the Global Burden of Disease (GBD) 2021 database. Incidence, mortality, and DALY rates per 100,000 population were calculated with 95% uncertainty intervals (UIs). Trend analysis used Joinpoint regression and estimated annual percentage change (EAPC). Decomposition analysis identified drivers of burden changes. A Bayesian age-period-cohort (BAPC) model projected future burden.

Results: In 2021, there were 91,507 TC cases, 11,388 deaths, and 560,921 DALYs globally. From 1990 to 2021, cases rose by 136%, deaths by 49%, and DALYs by 44%. Incidence increased from 1.45 to 2.31 per 100,000. The middle socio-demographic index (SDI) region showed the highest EAPCs for incidence (4.34%), mortality (1.07%), and DALYs (0.92%). The Caribbean had the fastest-growing incidence (EAPC = 5.71%). Nationally, the U.S. had the most cases (11,845), Monaco the highest incidence (32.89/100,000), and Qatar the steepest rise (EAPC = 10.25%). By 2035, incidence is projected to rise further, while mortality and DALY rates may decline.

Conclusion: The global burden of TC has increased markedly since 1990, especially in middle-SDI regions and the Caribbean. Although some areas have seen improvements, rising incidence highlights the need for targeted prevention and optimized care strategies.

N⁶-methyladenosine (m⁶A), as the most abundant RNA epitranscriptional modification in eukaryotes, its key component of the methyltransferase complex, METTL14, not only cooperates in catalyzing m⁶A deposition but also has functions independent of methyltransferase activity. This article systematically reviews the dual regulatory role of METTL14 in tumors and its molecular mechanisms, mainly organizing the relevant research in a logical sequence of "tumor suppressive effect - tumor promoting effect - controversial or context-dependent". Studies have shown that METTL14 often plays a tumor suppressive role in tumors such as hepatocellular carcinoma and colorectal cancer, while in pancreatic cancer and nasopharyngeal carcinoma, it mostly promotes malignant progression, showing a high degree of context dependence. This article focuses on two key mechanisms: on the one hand, METTL14 precisely regulates the processing, stability, and function of non-coding RNAs (including miRNAs, lncRNAs, and circRNAs) through m⁶A modification, reshaping the competitive endogenous RNA (ceRNA) network; on the other hand, it shapes an immunosuppressive tumor microenvironment by directly upregulating immune checkpoints such as PD-L1, mediating metabolism-immune interactions, and regulating the function of immune cells. Its functional duality also stems from the selective regulation of key pathways such as PI3K/AKT, as well as the differential interpretation by different m⁶A readers (such as YTHDF2 and IGF2BPs). Given the close association of these mechanisms with clinical prognosis, the expression level of METTL14 shows significant potential as a prognostic marker and therapeutic target; in the future, it is necessary to combine single-cell multi-omics and other technologies to analyze its dynamic regulatory network in specific tumor contexts and explore precise treatment strategies based on synthetic lethality or targeting downstream effector molecules.

Langerhans Cell Sarcoma (LCS) is an extremely rare and aggressive neoplasm with limited consensus on optimal treatment. We report the case of a 56-year-old woman with refractory Langerhans Cell Histiocytosis (LCH) that transformed into Langerhans Cell Sarcoma (LCS) who achieved complete remission following chemotherapy with cladribine, high-dose cytarabine, G-CSF, and mitoxantrone (CLAG-M), and subsequent allogeneic hematopoietic stem cell transplantation (HSCT). This case highlights the potential role of allogeneic HSCT as an effective therapeutic option for refractory LCS and underscores the importance of reporting additional cases to guide future management strategies in this rare malignancy.

Background: Reliable markers for predicting postoperative recurrence in high-risk stage II-III colorectal cancer remain limited. Dynamic changes in immunoglobulin G (IgG) may provide prognostic information beyond carcinoembryonic antigen (CEA).

Methods: This single-centre retrospective cohort study included 192 patients with high-risk stage II or III colorectal cancer who underwent curative resection between January 2021 and June 2023. The study evaluated whether dynamic postoperative monitoring of serum IgG predicts 2-year disease-free survival (DFS) compared with CEA. Serial IgG and CEA measurements within 24 months were categorised as favourable or unfavourable trajectories based on predefined thresholds and temporal trends. Patients were further stratified into four groups according to combined IgG and CEA dynamics. Survival was assessed using Kaplan-Meier analysis and Cox regression models.

Results: Among 192 eligible patients, 60 (31.3%) experienced recurrence or death within 2 years. Unfavourable IgG trajectories (n=82) were associated with significantly lower 2-year DFS than favourable trajectories (55% [95% CI 44-65] vs 82% [95% CI 73-88], log-rank P<0.01). CEA trajectories showed only borderline separation (67% [95% CI 55-77] vs 79% [95% CI 71-85], log-rank P = 0.06). Patients with both unfavourable IgG and CEA trajectories had the poorest outcomes (2-year DFS 31% [95% CI 16-47]). In multivariable analysis, an unfavourable IgG trajectory independently predicted recurrence or death (HR 2.05, 95% CI 1.32-3.18), whereas CEA trajectory was not significant.

Conclusion: Dynamic postoperative IgG monitoring is independently associated with disease recurrence in high-risk stage II-III colorectal cancer and offers incremental prognostic value beyond CEA. Incorporating serial IgG measurements may enhance postoperative risk stratification, although confirmation in prospective multicentre studies is warranted.

Immune checkpoint inhibitors (ICIs) are known to cause a wide spectrum of immune-related adverse events (irAEs). Among these, eosinophilic fasciitis (EF) is a rare, fibrosing disorder causing inflammatory infiltration of subcutaneous fat and fascia. It is characterized clinically by edema and subsequent induration and tightening of the skin and subcutaneous tissues. Several case reports have documented EF secondary to ICIs in patients on active treatment. Herein, we present two cases of delayed EF following treatment cessation with avelumab for metastatic urothelial carcinoma (Case 1) and following adjuvant nivolumab completion for stage IIIC melanoma (Case 2). Both patients had typical exam findings including erythema/edema of the extremities and trunk and diffuse thickening of subcutaneous fat and fascia, leading to severe respiratory restriction in Case 1. Both patients were diagnosed with EF by full-thickness skin biopsy showing sclerosis and lymphocytic infiltration of the subcutaneous fat and/or fascia. Only one of the two patients presented with definite eosinophilia. Both cases were treated with glucocorticoids and had early recurrence of symptoms post steroid taper, necessitating subsequent protracted steroid and steroid sparing agent use. Overall, we demonstrate the importance of considering delayed irAEs, specifically autoimmune fibrotic skin diseases even when ICI therapy has been discontinued. We underscore the need for collaboration between oncology and rheumatology as the scope of ICI treatments for cancer continues to expand.

Background: Neoadjuvant chemotherapy (NAC) is widely used in early-stage and locally advanced HER2-negative breast cancer, yet pathological complete response (pCR) is achieved in only a subset of patients. Reliable pretreatment biomarkers for predicting pCR are lacking, particularly for patients treated with standard anthracycline- and taxane-based regimens. Increasing evidence indicates that chemotherapy efficacy is closely linked to the tumor immune microenvironment, suggesting that immune-related molecular signatures may improve response prediction.

Methods: A total of 2,385 pretreatment HER2-negative breast cancer patients from ten GEO cohorts were included. GSE194040 (n = 743) was used for training, and nine independent cohorts (n = 1,642) were used for external validation. Differential expression analysis was performed separately in hormone receptor positive and negative subgroups, and genes showing concordant regulation between pCR and non-pCR cases were identified. Weighted gene co-expression network analysis (WGCNA) was applied to detect pCR-associated gene modules. Immune-related genes curated from the ImmPort database were intersected with candidate genes, followed by feature selection using least absolute shrinkage and selection operator regression, random forest, and support vector machine recursive feature elimination. An artificial neural network (ANN) model was constructed based on overlapping features and evaluated using receiver operating characteristic analysis. Immune infiltration was estimated by CIBERSORT, and transcription factor, competing endogenous RNA, and drug enrichment analyses were performed. Key genes were further validated by quantitative real-time PCR in pretreatment tumor tissues.

Results: Five immune-related genes (CCL2, CXCL10, CXCL13, HLA-E, and IGKV1D-8) were identified as robust predictors of pCR and used to build the ANN model. The model achieved an area under the curve of 0.858(95% CI: 0.829-0.888) in the training cohort and 0.773 (95% CI: 0.735-0.808) in the external validation cohorts, demonstrating s predictive performance across independent datasets. High expression of the five-gene signature was associated with increased infiltration of cytotoxic and antigen-presenting immune cells, consistent with an immune-activated tumor microenvironment, and was confirmed by qRT-PCR analysis.

Conclusion: This study establishes a rigorously validated ANN-based immune gene signature for predicting response to neoadjuvant chemotherapy in HER2-negative breast cancer, providing a potential tool for pretreatment risk stratifictableation and individualized therapeutic decision-making.

[This corrects the article DOI: 10.3389/fonc.2026.1740060.].

Background: Nodal involvement (N stage) is a key prognostic factor in prostate cancer (PCa). Conventional imaging and histopathology often have limited sensitivity and inter-observer variability. AI-based computational pathology, using multi-instance learning (MIL) and foundation models, offers a promising approach for accurate and interpretable N stage prediction from H&E-stained whole slide images (WSIs).

Methods: In this multicenter retrospective study, we developed a weakly supervised deep learning framework integrating MIL with domain-adapted foundation model encoders (UNI-v2, CONCH, ResNet-50) to predict N stage. WSIs from 280 RHWU patients were used for training and 306 TCGA patients for external validation. Attention heatmaps enabled interpretability, while transcriptomic analyses explored molecular correlates via differential expression and bioinformation analysis.

Results: The UNI-v2-based model achieved the highest performance (AUC 0.879 in RHWU, 0.850 in TCGA), surpassing CONCH and ResNet-50. Attention heatmaps highlighted tumor-stromal interfaces and poorly differentiated tumor clusters. Transcriptomic analysis identified 94 differentially expressed genes; upregulated genes were enriched in cell cycle, and immune pathways, while downregulated genes involved ion transport and metabolism.

Conclusions: This AI-MIL framework accurately predicts nodal involvement in PCa and provides biologically interpretable insights, supporting its potential as a precision oncology tool for risk stratification and treatment planning.

Introduction: Pilocytic astrocytomas are driven by BRAF and mitogen-activated protein kinase (MAPK) alterations, typically KIAA1549::BRAF fusions. A rare GTF2I::BRAF fusion has been described, but little is known about these cases.

Case report: Here, we report two cases with GTF2I::BRAF fusions. Case 1 is a 36-year-old man initially diagnosed with myxopapillary ependymoma at the conus medullaris with three recurrences over 23 years requiring two surgeries, three rounds of radiation therapy, and one round of lapatinib/temozolomide. A distant disease focus in T3/T4 was sampled and tested with modern diagnostic techniques revealing a pilocytic astrocytoma on histology and methylation profiling. The patient has subsequently had stable clinical and radiographic findings. Case 2 is another 36-year-old man initially diagnosed with meningitis and later neurosarcoid who underwent biopsy after 12 years when his spinal leptomeningeal disease continued to progress and an intraventricular non-enhancing nodule emerged as a separate focus. Sampling of the leptomeningeal disease led to a diagnosis of pilocytic astrocytoma by histology and a divergent methylation profile. The patient has remained neurologically stable under radiographic surveillance without any intervention.

Results: Radiographic, histological, and molecular data are presented for both cases and compared against the only other reported GTF2I::BRAF CNS case, as well as canonical versions of pilocytic astrocytoma.

Conclusion: To our knowledge, this is only the second case series highlighting a unique GTF2I::BRAF fusion and the first to describe it in adults in a spinal location. The manuscript contributes documentation of a rare fusion and tumor presentation to guide clinicians and potential research avenues.