This study aimed to investigate the impact of chronic inflammation (CI) on gastric cancer (GC) progression and the underlying molecular mechanisms. A subcutaneous xenograft model using 615-strain mice was established to evaluate the pro-tumorigenic effects of CI. Proteome Profiler Mouse XL Cytokine Array was used to screen for key pro-tumorigenic cytokines induced by CI, and ELISA was employed for validation. single-cell RNA sequencing(ScRNA-seq) was performed to identify the cellular source of CX3CL1 in GC tumor tissues. CCK-8 and colony formation assays were used to assess the effect of CX3CL1 on GC cell proliferation, while wound-healing and Transwell assays evaluated cell migration. ADAM10 expression was measured in gastric cancer cells and tissues via qRT-PCR, Western blot, and immunofluorescence staining. CI significantly accelerated gastric cancer progression. CX3CL1 expression was markedly higher in GC tissues than in normal gastric tissues, and high CX3CL1 expression was associated with poor prognosis in GC patients. CX3CL1 recombinant protein significantly promoted the proliferation and migration of GC cells, and these effects were attenuated by pharmacological inhibition of CX3CR1. Mechanistically, CI upregulated the expression of ADAM10, which plays a key role in converting membrane-bound CX3CL1 to its soluble form. This study provided evidence that chronic inflammation could promote tumor progression through the activation of ADAM10/CX3CL1 axis in gastric cancer.

Tumor-infiltrating B lymphocytes (TIL-Bs) are increasingly recognized as favorable prognostic markers in multiple cancer types and the mechanisms underlying this are being actively investigated. In this study of TIL-Bs, we identified CD79A as a reliable quantifier of B lymphocytes and evaluated transcriptomic data for 15 distinct tumors using 8,720 samples of treatment naïve patients from The Cancer Genome Atlas and normal tissues from Gene Tissue Expression. B-lymphocyte infiltration correlated with survival for some but not all tumors. In lung adenocarcinoma (LUAD), CD79A levels were strongly predictive of overall survival, while CD8A transcripts were not, indicating that leukocytic infiltration per se does not explain the B-cell's impact. Single-cell RNA sequencing and flow cytometry identified increased relative numbers of CD11c+ B cells in treatment-naïve LUAD patients compared to normal tissue and blood. In LUAD, CD11c+ TIL-Bs were localized near CD4+ T cells and in vitro stimulation with anti-IgG with/without CD40 agonist resulted in expansion and rapid differentiation. Stimulation also induced IL-12, IL-21, and TNF-α secretion, which are cytokines known to enhance antitumor immunity. Overall, the data indicte that CD11c+ TIL-Bs are a potential target for anticancer therapeutic approaches and/or a potential prognostic biomarker for cancer prognosis.

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related deaths globally. It results from polyp growth or ulcers formation in the colon or intestine lining. Genetic, environmental factors, unhealthy eating habits, and lifestyle choices contribute to CRC development. Genetic and epigenetic changes play a crucial role in tumor development. Homeobox (HOX) genes contain the homeodomain, encoding transcription factors that regulate gene expression. Paired Related Homeobox 1 (PRRX1) and Paired Related Homeobox 2(PRRX2), a homeobox genes, is overexpressed in diseases and involved in tumor metastasis, impacting cancer cell properties and metastasis. In this study, our goal was to analyze the presence of PRRX1and PRRX2 in both colorectal cancer and nearby normal tissues. The expression levels of PRRX1 and PRRX2 were evaluated in 100 colorectal tumor tissues and 100 adjacent control tissues using the Quantitative Real-Time PCR (qRT-PCR) method. Additionally, we assessed the diagnostic effectiveness of PRRX1 and PRRX2 by creating a receiver operating characteristic (ROC) curve. Our findings showed that the expression of PRRX1 and PRRX2 were significantly overexpress in colorectal cancer patients compared to the adjacent control group sample. Examination of clinicopathological characteristics of patients revealed varied correlations between PRRX1 and PRRX2 genes expressions and TMN stage (p<0.0001, p<0.0001). Also, the expression levels of PRRX1, PRRX2 between patients with LVI+ and those with LVI-, with p-values of p<0.0001, p<0.0001 for each. These findings suggest that PRRX1and PRRX2 levels could be used as possible diagnostic indicators for colorectal cancer.

Background Surgery is the standard treatment for oral cancer but often causes functional and cosmetic problems, and reoperation is difficult. Radiotherapy (RT) is less effective, with reirradiation limited by normal tissue tolerance and salvage surgery after RT carrying high complication risks. Systemic therapy is used for local recurrence but yields poor outcomes, underscoring the need for better options. Boron neutron capture therapy (BNCT) is an established method that selectively delivers high tumor doses. This study evaluated BNCT efficacy and safety in unresectable oral cancers not amenable to definitive RT. Methods This retrospective study included oral cancer patients treated with BNCT between June 2020 and June 2024 under the Japanese public health insurance system. Primary endpoints were best treatment response and incidence of adverse events (AEs), particularly severe oral mucositis (Grade ≥ 3 by Common Terminology Criteria for AEs version 5). Predictors of severe oral mucositis were also examined. Secondary endpoints included overall survival (OS), locoregional control (LRC), and progression free survival (PFS). Results Among 74 patients (follow-up period ≥3 months), the majority (73%) had recurrent cancer. The complete response rate was 50%. The major severe acute AE was severe oral mucositis (all Grade 3) in 26% of patients. The maximum oral mucosal dose and the number of dental metals were significant predictors of severe oral mucositis. The 2-year OS, LRC, and PFS rates were 49%, 52%, and 29%, respectively. Conclusion This study suggests that BNCT is an effective and safe treatment for unresectable oral cancers that cannot be definitively irradiated.

Glioblastoma (GBM) is the most prevalent type of malignant primary brain tumor. Preclinical research serves a key role in investigating the development and mechanism of GBM tumor. However, the dynamic and non‑invasive evaluation of tumors in animals faces challenges, such as the limited sensitivity of clinical instruments and insufficient spatial resolution for mouse brain tumors. The present study aimed to establish an in vivo mouse GBM model and evaluate the model using high resolution small animal positron emission tomography‑computed tomography (PET‑CT) and magnetic resonance imaging (MRI). Metabolism was compared between the normal brain and tumor tissue by using 1H‑magnetic resonance spectroscopy (1H‑MRS). T2‑weighted imaging (T2WI) MRI detected the tumor in the brain 7 days after injection of GL261 cells, with tumor sizes of 1.263, 4.917 and 13.85 mm3 on days 7, 14 and 21, respectively. 1H‑MRS demonstrated that the levels of tissue metabolites such as lactate and total choline increased, while those representing neurological function of the brain such as total N‑acetylaspartate decreased in tumor compared with the normal brain tissues. PET‑CT imaging confirmed the tumor detected by MRI. At 6‑120 min post 18F‑fluorodeoxyglucose (FDG) administration, the standard uptake value (SUV) in tumor tissue gradually increased, while the SUV value in normal brain tissue gradually decreased. SUV in the liver and kidneys decreased, while SUV in the bladder increased in a time‑dependent manner. Pharmacokinetic analysis showed that the distribution of FDG in brain and tumor tissue conformed to a two‑tissue compartment model. This model consists of a plasma compartment and two tissue compartments representing free FDG and phosphorylated FDG within brain or tumor tissue. The model parameters are defined as follows: Fractional blood volume (vB)=3.6%, k1 (forward transport rate)=1.844, k2 (reverse transport rate)=3.844 and k3 (phosphorylation rate)=0.280 in brain and vB=2.3%, k1=0.797, k2=2.722 and k3=0.319 in tumor tissue, respectively. The tumors observed by MRI and PET‑CT imaging were ultimately confirmed through morphological and pathological analysis. Compared with normal brain tissue, glioma tissue exhibited significantly elevated glucose transporter type 1 protein levels. In conclusion, the model was confirmed by high‑resolution small animal PET‑CT and MRI, as well as morphological and pathological approaches.

Background: HML-2 subgroup mobile genetic elements of the HERV-K family were described to participate in carcinogenesis processes, but their expression and epigenetic regulation in molecular subtypes of colorectal cancer (CRC) remain partly characterized. The present study aimed to evaluate the expression of HML-2 elements using RNA-sequencing data in paired tumor and normal intestinal tissue samples from 63 patients with CRC to identify patterns of the retrotransposons’ activity in different molecular subtypes (CMSs). Methods: RNA-sequencing and DNA methylation data were analyzed for paired CRC and normal tissue samples. HERV-K expression was assessed using three bioinformatics tools: Telescope (version 1.0.3), TEtranscripts (version 2.2.3), GeneTEFlow (version 2020). Molecular tumor subtypes were defined using the CMScaller (version 0.99.2) program. The results of the HML-2 loci expression analysis were supplemented with the HML-2 proteins expression data obtained by quantitative RT-PCR. Results: HML-2 expression assessment by GeneTEFlow (version 2020), TECount (version 2.2.3) and Telescope (version 1.0.3) showed high convergence: the Pearson correlation coefficient for each tool exceeded 0.88. Several HML-2 loci were identified as differentially expressed in CRC samples of different CMS. The PCR results confirmed an increase in HML-2 expression in tumor tissues. For all CMSs, an inverse association was detected between differential methylation of CpG sites and differential expression of HML-2 loci. Associations of HML-2 expressions with differentially expressed genes in which they are located were found, and for a number of such genes an inverse relationship between the expression level and the methylation level of their promoters were demonstrated, and data on the involvement in the pathogenesis of CRC were described: CR1, CD48, TTLL3, ABCC2 and ZNF420. Expression signatures associated with the activity of the RIG-I-like receptor signaling cascade were identified in CMS1–3 CRC samples, which may indicate the possible implementation of viral mimicry against the background of HML-2 activation. Conclusions: Analysis of the expression of HML-2 and its association with CpG methylation contributes to a comprehensive interpretation of the CRC pathogenesis mechanisms.

Fibrosis is a complex disorder characterized by the excessive deposition of extracellular matrix, which disrupts normal tissue architecture and compromises organ function. Fibrosis can affect any organ, with pulmonary fibrosis being one of the most common and life-threatening forms. Despite marked research efforts, effective antifibrotic therapies remain limited, largely due to an incomplete understanding of the underlying disease mechanisms. At the centre of fibrotic processes are fibroblasts, which are tissue-resident mesenchymal cells responsible for extracellular matrix production, tissue remodelling, wound healing and fibrosis. For decades, the biology of fibroblasts remained poorly understood, but advances in single-cell sequencing have recently provided deeper insights into their heterogeneity, plasticity and functional diversity. These insights have prompted renewed efforts to identify the core regulatory programmes that govern fibroblast states in health and disease. In this Review, we examine how immunological, mechanical and metabolic regulators influence fibroblast function in fibrosing interstitial lung diseases. We show how loss of stromal regulation through chronic inflammation, immune dysfunction, altered tissue biomechanics and metabolic stress can tip the balance from successful tissue repair to progressive fibrosis.

This study explored the interplay between vascular density and the immune microenvironment in medullary thyroid carcinoma (MTC) to elucidate their impact on tumor behavior. Using tissue microarray (TMA) analysis of 24 histopathologically confirmed MTC cases, we assessed immune cell infiltration (CD68+ macrophages, CD3+/CD4+/CD8+/CD20+ lymphocytes, granzyme B, and FOXP3+) and vascular markers (D2-40, CD31, and ERG) across tumor regions: center, interface, adjacent normal tissue, and metastases. Vascular density was quantified using ImageJ, while immune markers were analyzed using QuPath software. The The Key findings revealed distinct spatial heterogeneity in the vascular distribution. D2-40+ lymphatic vessel density was significantly elevated in adjacent normal tissue compared to the tumor center (p<0.05), whereas ERG+ microvessel density was the highest at the tumor interface. ERG+ vascular density at the interface was positively correlated with mast cell infiltration (Spearman=0.571, p=0.009). D2-40+ density in the tumor center was associated with CD8+ T-cell infiltration (Spearman=0.488, p=0.025), while interface D2-40+ density was correlated with CD3+ (Spearman=0.584, p=0.009), CD8+ (Spearman=0.508, p=0.022), and granzyme B+ cells (Spearman=0.482, p=0.031). CD31+ vascular density in adjacent normal tissues showed a positive relationship with FOXP3+ regulatory T cells (T-regs) (Spearman=0.456, p=0.05). Patients with distant metastases exhibited a higher D2-40+ density in tumor centers than in non-metastatic cases (p=0.024). These results underscore the dynamic relationship between vascular architecture and immune infiltration in MTC, highlighting region-specific interactions that may influence tumor progression. The elevated D2-40+ density in metastatic cases and distinct immuno-vascular correlations suggest potential prognostic markers and therapeutic targets.

Background Glioma, a highly heterogeneous primary intracranial malignancy, features an immunosuppressive tumor microenvironment (TME) dominated by tumor-associated macrophages (TAMs). These glioma-associated macrophages (GAMs) critically drive disease progression, yet their metabolic reprogramming and clinical prognostic potential remain incompletely characterized. This study aimed to stratify GAMs by metabolic profiles and elucidate their clinical relevance, providing a framework for novel therapeutic strategies. Methods We performed integrated multi-omics analysis of glioma single-cell RNA sequencing (scRNA-seq), bulk transcriptome sequencing, and clinical data. GAMs were stratified using metabolic pathway enrichment scores, and their abundance was correlated with patient prognosis. Supervised machine learning algorithms identified prognostic signature genes to construct a metabolic risk prediction model. Patients were stratified into high- and low-risk groups based on model-derived risk scores. Comprehensive profiling compared these groups across three dimensions: (i) dysregulated signaling pathways, (ii) tumor microenvironment characteristics, and (iii) genomic aberrations. Western blot (WB) analysis validated core gene expression in glioblastoma tumor tissues versus adjacent normal brain tissues. Results This study reclassified GAMs into four metabolic subtypes—Glycolipid-Signaling (GSM), Detoxification and Energic (DEM), Polymetabolic (PmM), and Glycolipid Metabolism/Immunoregulatory (GMIM)—with DEMs exhibiting terminal differentiation, enrichment in detoxification/energy pathways, and significant correlation with advanced tumor grades and poor survival (p &amp;lt; 0.05). Machine learning leveraging DEM signature genes identified six core prognostic markers (CLIC1, FABP5, FCER1G, S100A8, S100A9, SPP1) and optimized a Stepwise Cox + Random Survival Forest model (C-index = 0.71). Applying this model, we identified high-risk gliomas exhibiting a paradoxical tumor microenvironment characterized by elevated immune cell infiltration and enhanced immunogenicity, yet impaired T-cell cytotoxicity. Concurrently, high-risk gliomas demonstrated hyperactivation of pro-tumorigenic pathways (e.g., mTOR, MAPK) and frequent EGFR amplification. Integration with EGFR amplification and IDH1 mutation status enhanced clinical prognostication. Western blot validation confirmed significant upregulation of all six core proteins in glioblastoma versus adjacent normal brain tissues. Conclusions Metabolic subtyping identifies DEMs as critical drivers of glioma progression. The DEM-derived risk model, combined with EGFR/IDH status, provides a clinically actionable tool for prognosis and targeted therapy development.

Background Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, demonstrates escalating global incidence and mortality trends. Although emerging evidence suggests that TBC1 domain family member 16 (TBC1D16) significantly contributes to tumorigenesis and malignant progression across multiple cancer types, the relationship between TBC1D16 and HCC remains poorly understood. Our study aims to elucidate the functional role of TBC1D16 in HCC and its potential clinical value. Methods The expression of TBC1D16 in HCC was analyzed through TCGA and GEO databases, verified via qRT-PCR and Western blotting. Kaplan–Meier survival curves and Cox regression analysis assessed its correlation with HCC prognosis. Cell functional assays explored the impact of TBC1D16 on HCC progression. Potential transcription factors regulating TBC1D16 were identified through transcription factor databases. RNA-seq, KEGG, and GSEA identified TBC1D16-related signaling pathways, which were confirmed by biochemical validation. Finally, TIMER, ssGSEA, TCIA, and GDSC databases were harnessed to predict the impact of immunotherapy and targeted drug therapy. Results TBC1D16 expression is higher in HCC tissue than in adjacent normal tissue and is correlated with adverse prognosis of HCC patients. Silencing TBC1D16 reduced the proliferation, migration, and invasion of HCC cells. The expression of TBC1D16 is regulated by SP1.TBC1D16 expression inhibits NF-κB signaling, potentially serving as a mechanism contributing to HCC. Furthermore, TBC1D16 expression also affects immunotherapy responses and drug sensitivity. Conclusion TBC1D16 upregulation in HCC is linked to poor prognosis and enhances tumor invasiveness, silencing TBC1D16 activates NF-κB signaling, indicating its potential role in HCC diagnosis.

Proton therapy, by leveraging its unique physical characteristic of the Bragg peak, enables high-precision dose delivery to the tumor target while effectively protecting surrounding normal tissues, and has become an important representative of advanced radiotherapy. This review aims to systematically summarize key technological breakthroughs in recent years that have driven the progress of proton therapy, including compact superconducting accelerators, pencil beam scanning (PBS), image-guided proton therapy (IGPT), and the transformative ultra-high dose rate FLASH radiotherapy, while highlighting the role of artificial intelligence (AI) in advancing proton therapy toward real-time adaptive precision radiotherapy. The article also explores the global distribution and development status of proton centers, with a specific analysis of China’s notable advancements as an emerging market in center construction, equipment localization, and the treatment of characteristic local tumor types. Moving forward, it is essential to continue promoting technological integration and innovation, strengthen high-quality clinical research, and develop a more accessible, intelligent, and personalized proton therapy system to achieve broader clinical application and patient benefit.

Objective.The LET trilemma-an inherent conflict between target dose homogeneity, range robustness, and high dose-averaged linear energy transfer (LETd)-poses a major challenge in treatment optimization. To ensure accurate beam delivery in multi-ion therapy, this study evaluated the effects of range and setup uncertainties on LETd-optimized treatment plans and explored strategies to overcome this trilemma, framed within the phase I LETdescalation trial for head and neck cancers.Approach.Six head and neck cancer patients representing diverse tumors were selected. Multi-ion therapy plans using carbon-, oxygen-, and neon-ion beams were optimized to achieve a target LETdof 90 keV μm-1(the final LETdlevel of the phase I trial). These plans were recalculated to incorporate systematic range uncertainty (±2.5%) and random daily setup variations (mean, 0.45 mm; standard deviation, 0.23 mm) across the 16 fractions, and their combined effects on the dose and LETddistributions were evaluated. Additionally, to explore strategies to enhance plan robustness, five modified plans were evaluated for one patient identified as particularly susceptible to these uncertainties.Main Results.Range uncertainty was the dominant contributor to degraded plan quality, substantially outweighing setup uncertainty. A small, centrally located tumor was most susceptible, exhibiting dose inhomogeneity of approximately 11%, while LETdvariations were approximately 3 keV μm-1. The most effective mitigation strategy involved replacing the original carbon-oxygen combination with oxygen ions for two beam ports, reducing dose inhomogeneity by more than 7% while maintaining normal tissue sparing adjacent to the target.Significance.Optimization toward achieving higher LETdmakes treatment plans susceptible to range uncertainty, leading to dose degradation within small, deep-seated tumors. Employing heavier ions is an effective strategy to overcome this challenge, enabling robust target coverage by leveraging their inherently higher LETdwhile sparing normal tissues. These findings provide a key rationale for ion selection in the design of robust multi-ion therapy.

The acidic tumor microenvironment (TME) in solid tumors, driven by abnormal metabolism and lactic acid accumulation, suppresses chimeric antigen receptor-T (CAR-T) cell efficacy while posing safety risks from on-target, off-tumor toxicity (OTOT). This study aims to develop a novel CAR-T technology that leverages lactic acid as a tumor-specific trigger to achieve precise control of CAR activity. The objective is to enable adaptation to the acidic TME while maintaining robust anti-tumor efficacy and mitigating OTOT. We engineered a lactic acid-responsive promoter (LARP) using RNA sequencing-identified lactic acid-sensitive genes. This promoter was integrated into HER2-targeting CAR to construct LAR CAR-T cells. CAR expression dynamics under acidic vs neutral conditions were quantified via flow cytometry. Phenotypic profiling (memory markers), in vitro cytotoxicity, and cytokine secretion were assessed. In vivo OTOT was evaluated in our previously constructed humanized HER2 mice, while anti-tumor efficacy and OTOT were further tested in this mouse model bearing tumors. Our findings demonstrate that the LARP responds to lactic acid, leading to increased CAR expression in acidic conditions. The ex vivo-expanded LAR CAR-T cells exhibited an enhanced memory phenotype and superior tumor-killing capacity in vitro under acidity. In vivo, LAR CAR-T cells achieved tumor eradication comparable to conventional CAR-T cells and exhibited significantly enhanced safety profiles, characterized by the absence of acute hepatotoxicity and minimal off-target organ toxicity. Our LARP strategy exploits tumor acidity as a precise low/high switch for CAR-T cells. By restricting potent CAR expression to the acidic TME while minimizing activity in normal tissues, LAR CAR-T overcomes key barriers of efficacy and OTOT in solid tumors. This lactic acid-sensing paradigm offers a clinically translatable platform for precise immunotherapy.

Aspects of the gut microbiome, including presence of specific bacterial species and overall community structure, have been linked to the etiology and prognosis of colorectal cancer (CRC). Less is known about the epidemiologic risk factors that are associated with the composition of the microbiota in invasive colorectal tumors. Using tumor and paired normal colorectal tissue samples from a subset of participants in the population-based Seattle Colon Cancer Family Registry, we compared the presence of Fusobacterium nucleatum (F. nucleatum) (n = 898) measured via droplet digital PCR and alpha diversity (Shannon index) (n = 611) measured via 16S rRNA gene sequencing in colorectal tissue across demographics, health behaviors, and neighborhood socioeconomic status (nSES). Normalized counts of F. nucleatum were consistently higher in tumor tissue than in patient-matched normal tissue across all risk factors, while alpha diversity was lower. Female sex was associated with high presence and enrichment of F. nucleatum in tumor tissue (odds ratio [OR] 1.61; 95% confidence interval [CI] 1.02, 2.54 and OR 1.58, 95% CI 1.10, 2.27, respectively). Relative to those aged 40-49years, the youngest age group (< 40years) had lower alpha diversity in tumor tissue (OR for highest vs. lowest tertile: 0.33; 95% 0.13, 0.83). Other factors, including diet, were not related to F. nucleatum presence or tumor tissue alpha diversity. By uncovering epidemiologic risk factors for F. nucleatum presence and bacterial diversity in the intratumoral microbiota, this work informs our understanding of associations of the gut microbiota with CRC etiology and outcomes.

Inherited genomic susceptibility and associated transcriptomic patterns are crucial players in lung cancer etiology. Lung cancer susceptibility is getting rising attention in carcinogenesis. The present study aimed to investigate unique clinical features and transcriptomic profile in patients with familial lung cancer (FLC) in Yunnan-Guizhou Plateau, Wumeng-Mountain area of China. 1,823 local lung cancer patients were enrolled (762 FLC, 1061 Sporadic). Clinicopathologic parameters were analyzed and summarized. 43 lung tissue samples (the adjacent nonmalignant tissue) were selected for Transcriptome/RNA-seq, the differential gene expression patterns were analyzed, significant functions and pathways were enriched and studied. Our FLC cohort showed unique characters: younger age; increased rate of adenocarcinoma, and early-stage cases; unbalance in blood types, anatomic sites and co-existing diseases; highlighted with significantly elevated comorbidity and early-onset of hypertension in FLC + population. Notably, our FLC + group exhibited a higher rate of bilateral lung cancers and multiple pulmonary nodules; beside, were more likely to develop different cysts, polyps, hyperplasia at a younger age. The transcriptome found that immune-related functions & pathways were significantly enriched in the familial cohort. E.g. "immune cells recruitment" with higher Neutrophils/ lower CD4 memory T cells. Collectively, these transcriptomic differences suggested: individuals with FLC may have baseline alterations in immune regulation, which could reflect a compromised immune surveillance or dysregulated inflammatory tone in their normal lung tissue. For the key gene, MUC16 may contribute to this process by influencing the assembly, structure & dynamical functions of pulmonary epithelial cilium; which could potentially impair mucociliary clearance, leading to prolonged retention of pollutants and carcinogens in the lung microenvironment. Hereditary factors likely contribute to the susceptibility to both lung cancer and hypertension in this population, while chronic exposure to local air pollution may further promote their early-onset and comorbidity. Our findings highlighted the potential significance of MUC16 in familial lung cancer or even early-onset lung cancer; and provided useful data for early screening and personalized treatment strategies for lung cancer.

mRNA-4157 (V940) is an individualized cancer vaccine designed to stimulate potent immune responses against patient-specific tumor neoantigens. Building on the rapid design capability, safety profile, and immunogenicity demonstrated by mRNA vaccines during the COVID-19 pandemic, V940 represents a significant advance in personalized immunotherapy. It is generated through sequencing of tumor and matched normal tissues, computational prediction of up to 34 top-ranked neoantigens, and formulation of an optimized mRNA construct in lipid nanoparticles. Once delivered, the mRNA is translated in host antigen-presenting cells, initiating antigen processing, presentation, and activation of CD8+ and CD4+ T cells that target tumor cells carrying those mutations. Advantages include rapid design cycles, polyepitope targeting, and a non-integrating platform, while challenges include time-sensitive manufacturing, cold chain requirements, imperfect neoantigen prediction, reduced efficacy in low-mutation-burden tumors, and the immunosuppressive tumor microenvironment. Current development focuses on refining antigen prediction algorithms, combining with synergistic therapies such as checkpoint inhibitors, radiation, or innate agonists, and expanding use into earlier-stage cancers. V940’s modular, mutation-guided approach offers a template for future cancer vaccines and the potential to transform treatment paradigms across multiple malignancies.

Predictive and prognostic value of a glucose metabolism disorder and immune-related gene signature in glioma.

Angiogenesis, the production of new blood capillaries from pre-existing vasculature, is an important mechanism necessary for cancer progression and metastasis. This process may be regulated by the balance of pro-angiogenic and anti-angiogenic factors. The disruption of this balance leads to the induction of angiogenesis. Thus, there is a high necessity to identify these angiogenesis-related genes. In this study, we have used GeneCards database to obtain a list of angiogenesis-related genes followed by construction of protein-protein interaction (PPI) network using STRING database. Out of 37 angiogenesis-related genes, a single-gene cluster containing 27 genes was identified using MCODE analysis. The top ten hub genes were identified as FGF2, HIF1A, VEGFC, VEGFA, MMP9, THBS1, MMP2, KDR, IL6, and NOS, which were further analyzed. FunRich application was used to perform gene enrichment analysis and identify top interactors by constructing an interaction map. PPI map of each individual hub gene was constructed using search tool for the retrieval of interacting genes/proteins (STRING) database. The expression levels of each individual hub gene in HCC (liver hepatocellular carcinoma-LIHC dataset) and normal tissue were analyzed using the gene expression profiling interactive analysis 2 (GEPIA2) portal. The prognostic value of the hub genes was analyzed using Kaplan-Meier survival plot. The translational-level expression was analyzed using the IHC section images from the Human Protein Atlas (HPA) database. Thus, targeting these factors for therapy, diagnosis, or prognosis could be a key strategies in the field of oncology.

Lung cancer is a highly malignant tumor and prone to recurrence and metastasis. Adenocarcinoma is the most common subtype. LIM zinc finger domain containing 2 (LIMS2) was reported to inhibit growth and metastasis of several tumors, while its role in lung adenocarcinoma remains unclear. This study aims to expound the function of LIMS2 in lung adenocarcinoma. The analysis from medical databanks showed that LIMS2 was lowly expressed in lung adenocarcinoma specimens, compared with the normal lung tissues, and our clinical data demonstrated that LIMS2 expression was associated with TNM stage of lung adenocarcinoma patients. Gain- and loss-of-function experiments revealed that LIMS2 suppressed proliferation, invasion, migration, epithelial-mesenchymal transition of lung adenocarcinoma cells, delayed xenograft and orthotopic growth, and blocked distant metastasis and lymph infiltration in nude mice. The medium supernatant from LIMS2-overexpressed lung adenocarcinoma cells intercepted the activation of fibroblasts from lung cancer. The co-IP results demonstrated that an E3 ubiquitin ligase ring finger and CHY zinc finger domain containing 1 (RCHY1) interacted with LIMS2, and mediated its K48 ubiquitination and degradation. LIMS2 overexpression reversed the promoting effects of RCHY1 on proliferation, migration and lung cancer-fibroblast activation of lung adenocarcinoma cells. In conclusion, decreased LIMS2 may mediate the tumor-promoting role of RCHY1 in lung adenocarcinoma cells. Implications: These findings may provide novel diagnostic markers and therapeutic targets for lung adenocarcinoma in clinic.

Background and Objectives: Glioblastoma (GBM) is the most aggressive form of primary brain tumor, characterised by high recurrence rates and poor patient prognosis. This study aimed to identify gene-expression signatures and molecular networks associated with primary and recurrent GBM to better understand the biological mechanisms underlying tumor progression. Materials and Methods: Gene expression analysis of TCGA data was conducted to identify differentially expressed genes across tumor, recurrent, and normal brain tissues. Analysis of overlapping differentially expressed gene sets revealed both common and specific gene-expression profiles across the groups, highlighting genes potentially involved in GBM recurrence. Gene network and canonical pathway analyses were performed using Ingenuity Pathway Analysis (IPA) to identify key pathways and cellular functions altered in GBM. Results: Our data identified distinct molecular signatures in tumor, recurrent, and normal brain samples, highlighting dysregulated genes associated with cellular growth, proliferation, and movement. Transcriptomic stratification revealed progressive tumor- and recurrence-adapted states, with composite Tumor Scores (TS) and Recurrence Scores (RS) classifying samples into four classes: normal-like, proliferative, transitional, and recurrence-adapted tumor states. Conclusions: These findings provide insights into the signaling networks and biological mechanisms underlying GBM recurrence and may guide the identification of potential therapeutic targets to improve the management of this malignancy.