Breast cancer heterogeneity necessitates robust prognostic biomarkers and therapeutic targets. This study aimed to identify key molecular drivers through integrative multi-omics approaches and validate their clinical relevance.

We combined differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning (StepCox-Random Survival Forest [RSF]) to screen prognostic signatures across TCGA, GEO (GSE42568, GSE9893, GSE7390), and METABRIC datasets. Immune microenvironment characterization utilized ESTIMATE, CIBERSORT, and functional enrichment analyses. Mechanistic validation included single-cell RNA sequencing, in vitro/in vivo experiments, and clinical cohort profiling.

WGCNA identified 102 hub genes linked to breast cancer progression. Machine learning optimization yielded a 3-gene signature (EGR3, RECQL4, MMP1) with superior prognostic stratification. Multi-cohort validation confirmed signature robustness. The C2 subtype, defined by high-risk scores, exhibited an immunosuppressive microenvironment with elevated PD-L1/LAG3/TIGIT and M2 macrophage enrichment. EGR3 emerged as a pivotal tumor suppressor: its expression inversely correlated with tumor stage and positively associated with CD8⁺ T cell infiltration. EGR3-high patients showed prolonged survival and enhanced immunotherapy response. Functional studies demonstrated EGR3 overexpression suppressed tumor growth and activated CD8⁺ T cells.

Our integrative framework established a machine learning-optimized 3-gene prognostic model with cross-platform reliability. EGR3 was validated as a dual-function regulator of tumor suppression and immunomodulation, offering a novel therapeutic target for breast cancer, particularly in immunologically "cold" triple-negative subtypes.

One of the main hurdles in solid tumors to the limited response of immunotherapy is the lack of sufficient T-cell infiltrate. This study aims to construct an iRGD-modified BiTE-directed T-cell therapeutic approach to enhance the treatment efficacy against KRAS G12V-mutated pancreatic cancer.

We used a novel bispecific T-cell engager (BiTE) targeting the HLA-A2/KRAS G12V complex and CD3 (HLA-A2/KRAS G12V-CD3 BiTE). By modifying with iRGD, we induced BiTE-mediated inward flow of activated effector T cells, specifically targeting the KRAS G12V mutation and improving tumor tissue penetration to address the problem of limited efficacy due to insufficient effector cells infiltration.

The results demonstrated that iRGD modification could promote tumor-specific lymphocyte infiltration and accumulation in tumor tissue, significantly inhibit tumor growth, and prolong survival in a xenograft pancreatic tumor model. This dual-action approach enhances T-cell infiltration by promoting transvascular and stromal penetration, greatly enhancing the efficacy of bispecific antibodies in solid tumors, leading to effective tumor eradication.

These findings strongly suggest further clinical validation of this iRGD-modified BiTE-directed T-cell therapeutic approach, potentially offering a more effective treatment option for patients with pancreatic cancer and other solid tumors.

Cancers of the gastrointestinal (GI) tract rank among the most commonly diagnosed malignancies worldwide, posing a heavy burden on public health. Therapeutic tumor vaccines have garnered significant interest due to their ability to promote tumor regression, eliminate minimal residual disease, create enduring immune memory, and minimize non-specific adverse effects. Recently, the integration of nanotechnology into cancer immunotherapy, particularly through the development of nanovaccines, represents a transformative approach to treating GI cancers. This review outlines the significant advancements in the design and application of nanovaccines, emphasizing the mechanisms by which these nanovaccines deliver tumor-specific antigens and immunostimulatory adjuvants, ensuring effective activation of immune responses. Despite the promise these innovative therapies hold, challenges remain, including efficient antigen delivery, safety concerns, and the complexities associated with regulatory compliance. This comprehensive analysis highlights the potential of nanovaccines in transforming treatment paradigms for GI cancers while underscoring the need for collaborative efforts to accelerate their clinical translation.

Thoracic tumors, including lung cancer, breast cancer, and thymoma, usually present poor outcomes. The current treatment methods for thoracic tumors have low efficacy and are associated with severe adverse reactions. Molecular targeted therapy and immunotherapy offer new possibilities for the treatment of thoracic tumors. In this review, we have summarized the latest research on these novel therapeutic strategies, and discussed their clinical applications, challenges, and possible countermeasures. This review offers a theoretical basis for improving the outcomes of thoracic tumor patients, along with future research prospects.

The gut microbiome is a critical regulator of systemic immunity and a major modulator of response to cancer immunotherapy with immune checkpoint inhibitors (ICIs). However, the clinical implementation of microbiome-inspired therapies that leverage these associations have proven challenging. Probiotics-live microorganisms thought to confer health benefits as part of food or food supplements-have gained increasing attention as readily testable, low-toxicity agents with potential of favorably influencing host-microbiome-immune interactions in the context of cancer immunotherapy. In this review, we critically evaluate the growing body of evidence supporting the role of probiotics in enhancing ICI efficacy and summarize published and ongoing clinical trials formally testing their role as adjuncts to cancer immunotherapy. Probiotics have been shown in preclinical murine models to exert immunomodulatory effects, including activation and maturation of dendritic cells, enhancement of MHC-I-mediated antigen presentation, modulation of cytokine profiles, and promotion of pro-inflammatory macrophage polarization. Probiotics also regulate adaptive immunity via microbial metabolites such as short-chain fatty acids (SCFAs), inosine, and tryptophan derivatives that support effector T cell activation and reduce T cell exhaustion. Cross-reactivity between microbial and tumor-associated antigens (molecular mimicry) further underscores the potential of probiotic strains to stimulate antitumor responses. In these models, supplementation with specific bacterial strains such as Bifidobacterium spp., Lactobacillus spp., Clostridium butyricum, and Akkermansia muciniphila enhanced ICI responses across tumor types including melanoma, lung cancer, and colorectal cancer. These findings are in part supported by early-phase clinical studies and retrospective cohorts, particularly in lung and renal cancers, where probiotic use has been associated with improved progression-free and overall survival. However, most clinical data are observational, and the field lacks standardized probiotic formulations and dosing protocols. To transition probiotics from food supplements to clinically validated immunotherapy adjuncts, rigorous mechanistic, translational, and clinical studies are necessary. These approaches have the potential to define mechanism-of-action, identify immunologically active strains, and inform rational clinical trial design. With careful development, probiotics hold promise as cost-effective, scalable, and personalized tools to optimize the efficacy and safety of cancer immunotherapy.

Leiomyosarcoma (LMS) is a mesenchymal neoplasm accounting for 20% of all soft tissue sarcomas (STS), with a particularly rare localization in the muscular layer of the venous vessels. The case report presents a patient with non-metastatic LMS of the right renal vein, spreading intraluminally, and reaching the right atrium of the heart, supplemented with a review of the state of knowledge. The patient underwent radical treatment, including radical nephrectomy with en bloc thrombectomy under extracorporeal circulation without circulatory arrest and deep hypothermia. Histopathological examination diagnosed LMS and negative surgical margins. A computed tomography (CT) scan performed on the 45th postoperative day detected no early recurrence or metastatic features. The world literature describes 78 cases of renal vein (RV) LMS. Surgical treatment has the greatest overall survival (OS) impact. Adjuvant systemic treatment and radiotherapy do not improve OS outcomes, having only palliative significance.

DDB1 and CUL4-associated factor 7 (DCAF7) is a WD-repeat adaptor that recruits substrates to the CUL4DDB1 ubiquitinligase complex, but its pan-cancer relevance and mechanistic contribution to tumor progression remain unclear.

Multi-omics datasets (genomic, transcriptomic, epigenomic, proteomic and single-cell) from 33 tumor types were integrated to define DCAF7 expression, regulation, and clinical significance. Somatic alterations and copy-number variation were analysed across cohorts, and promoter methylation and RNA modification signatures were interrogated. Immune associations were assessed by computational deconvolution and checkpoint-gene profiling. Pathway and network analyses were performed to infer DCAF7-linked programmes. Mechanistic and functional validation was conducted in hepatocellular carcinoma (LIHC) cell lines (HepG2, Huh7) using DCAF7 perturbation and pharmacologic Wnt inhibition.

DCAF7 was overexpressed in most cancers, consistent with copy-number gain, focal promoter hypomethylation and putative m⁶A-linked post-transcriptional regulation, whereas hypermethylation at two CpG loci predicted poor prognosis in LIHC. DCAF7 alterations, predominantly amplifications, were associated with shorter overall survival in LIHC and positively correlated with DCAF7 mRNA abundance across cohorts. Immunogenomic analyses linked high DCAF7 to CD4⁺ T-cell enrichment, broad upregulation of checkpoint genes (PD-1/PD-L1, CTLA-4, TIGIT), and increased tumour mutational burden, microsatellite instability and neoantigen load, suggesting an immune-evasive phenotype. Network and enrichment analyses converged on canonical Wnt/β-catenin, Hippo and cell-cycle programs. In vitro, DCAF7 promoted LIHC cell proliferation and migration by stabilising β-catenin via increased inhibitory Ser9 phosphorylation of GSK-3β, thereby inducing c-Myc and cyclin D1; DCAF7 knockdown or the Wnt inhibitor XAV939 attenuated these effects. Drug-response modelling further predicted increased sensitivity of DCAF7-high tumours to 17-AAG, docetaxel and alsterpaullone.

DCAF7 is frequently activated by genetic and epigenetic mechanisms across cancers, associates with an immunotherapy-relevant tumour immune milieu, and drives Wnt/β-catenindependent malignant phenotypes in LIHC. These findings support DCAF7 as a prognostic biomarker and a candidate therapeutic target, particularly for stratified intervention in LIHC.

DCAF7 is up-regulated in various tumours and correlates with poor prognosis, particularly in LIHC. High DCAF7 expression is linked to CD4⁺ T cell infiltration, up-regulation of immune checkpoint genes and increased tumour mutational burden, suggesting a role in tumour immune escape. DCAF7 stabilises β-catenin by enhancing GSK-3β Ser9 phosphorylation, thereby driving c-Myc/cyclin D1 expression and contributing to proliferation and migration in LIHC. DCAF7-high tumours demonstrate therapeutic vulnerability to 17-AAG, docetaxel and CDK/GSK-3 inhibitor, revealing potential targeted treatment strategies.

Pre-therapeutic UGT1A1 genotyping is increasingly performed in patients receiving irinotecan, as its active metabolite SN-38 is primarily cleared through UGT1A1-mediated glucuronidation. Patients with the UGT1A1*28/*28 genotype exhibit reduced UGT1A1 activity, leading to increased SN-38 exposure and a higher risk of adverse events such as neutropenia and diarrhea. Although sacituzumab govitecan contains the same active metabolite as irinotecan, routine UGT1A1 genotyping prior to treatment with this drug is not yet standard practice and is not included in its product information. The aim of this study was to assess whether pre-therapeutic UGT1A1 genotyping may also benefit patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative and triple-negative breast cancer who are treated with sacituzumab govitecan. A literature search was conducted to identify relevant studies assessing the impact of UGT1A1 genotyping on the safety and efficacy of sacituzumab govitecan treatment. A meta-analysis was performed on selected studies. Additionally, a pharmacological analysis was performed using public data comparing SN-38 levels in patients treated with sacituzumab govitecan to those receiving irinotecan. The meta-analysis shows that grade ≥ 3 adverse events, including neutropenia, febrile neutropenia, and diarrhea, occurred more frequently in patients with the *28/*28 genotype. Furthermore, a statistically significant increased risk was found for developing grade ≥ 3 diarrhea or febrile neutropenia in this group. Although the meta-analysis was underpowered due to small sample sizes, the pharmacological analysis demonstrated higher SN-38 levels in patients treated with sacituzumab govitecan, supporting the rationale for UGT1A1 genotyping in this context.

Breast cancer (BRCA)'s molecular heterogeneity complicates prognosis and treatment. Tumor Doubling Time (TDT), a critical growth rate metric with clinical and prognostic significance, offers untapped potential as a biomarker to decode heterogeneity and improve therapeutic strategies.

Based on transcriptomic and clinical data from TCGA and GEO, this study analyzed BRCA. Through differential expression and survival analyses, differentially expressed tumor doubling time-related genes (TDTRGs) with prognostic significance were identified. Consensus clustering using these genes defined two molecular subtypes. A prognostic risk model was constructed and validated through LASSO and multivariate Cox regression. Comprehensive evaluation was performed on these molecular subtypes and risk groups, encompassing immune infiltration (ssGSEA, CIBERSORT, ESTIMATE), mutational burden, response to immunotherapy (IMvigor210), and drug sensitivity (CellMiner, pRRophetic).

This study constructed and validated an 8 gene prognostic risk model demonstrating robust predictive performance in both training (AUCs: 1-year=0.703, 3-year=0.693, 5-year=0.671) and validation cohorts. The low-risk group showed significantly enhanced immune cell infiltration, elevated immune checkpoint expression, and improved response to immunotherapy. Conversely, the high-risk group displayed increased tumor purity, metabolic reprogramming (e.g., respiratory electron transport), genomic instability, higher tumor mutational burden, and differential drug sensitivity (e.g., resistance to Gemcitabine/Tamoxifen).

This study establishes a novel TDTRGs framework for BRCA molecular classification and validated prognostic stratification. It reveals key disparities in immune microenvironment and genomic stability, enhancing understanding and guiding personalized therapeutic strategies.

Data on outcomes of superficial nonampullary duodenal tumors (SNADETs) are limited. We evaluated clinical features, outcomes, and complications of endoscopic resection (ER) in a large single-center cohort.

Patients who underwent ER for SNADETs between 2008 and 2023 were retrospectively reviewed. Clinicopathologic features, resection outcomes, adverse events, and recurrence were analyzed.

A total of 176 SNADETs from 163 patients (mean age, 57±13 years; 56.4% male) were included. The median follow-up duration was 22 months. The mean lesion size was 9.8±5.4 mm. ER methods were cold snare polypectomy (CSP) (n=29), cold endoscopic mucosal resection (EMR) (n=42), hot EMR (n=83), endoscopic submucosal dissection (ESD) (n=13), and underwater EMR (n=8). En bloc and histologic curative resection rates were 85.7% and 91.5%, respectively. Bleeding occurred in nine patients (5.1%), and perforation occurred in three patients (1.7%); both were mostly managed endoscopically. Bleeding was more common in the second portion of duodenum, and with hot EMR and ESD, whereas no bleeding occurred after CSP or underwater EMR. CSP and underwater EMR showed the shortest procedure times, whereas cold EMR and hot EMR had longer procedure times; ESD had the longest procedure time. Local recurrence occurred after en bloc curative ESD in one patient (0.6%).

ER is effective and safe for SNADETs, achieving high curative resection rates, low recurrence, and acceptable complication risks. Selection of resection method should be individualized, with cold EMR and underwater EMR offering safe and efficient alternatives for the treatment of smaller lesions, while ESD may be reserved for the treatment of larger lesions or complex cases.