Methyl-CpG-binding domain protein 2 (MBD2) is a key epigenetic regulator implicated in tumorigenesis by repressing tumor suppressor genes by recognizing DNA methylation marks and recruiting specific histone-modifying enzymes and chromatin remodeling complexes. Although KCC-07 has been identified as a potent selective MBD2 inhibitor, its cytotoxic effects on various cancer cells remain largely unexplored. In the current study, we have examined the anti-proliferative and cytotoxic activities of KCC-07 on breast cancer (MCF-7), prostate cancer (PC-3), hepatocellular carcinoma (Huh-7), and osteosarcoma (U2-OS) cell lines, along with human skin fibroblasts (HFF-1) as a non-malignant control.

Treatment of these cells with KCC-07 induced dose- and time-dependent cytotoxicity, notably reducing viability in Huh-7 and PC-3 cells. Flow cytometry analyses revealed that KCC-07 primarily triggered necrosis in Huh-7 and apoptosis in PC-3 cells. Furthermore, KCC-07 substantially downregulated MBD2-associated oncogenic targets such as WNT1, CCND1, and ERK1/2 in Huh-7 and PC-3 cells without altering MBD2 transcription.

These findings suggest that KCC-07 elicited a considerable cytotoxicity on cancer cells, likely modulating the expression of MBD2-related genes, highlighting its potential as a candidate for cancer therapy.

Patients with cancer are at a significantly higher risk of sepsis, which is associated with substantially increased morbidity and mortality. However, the intrinsic molecular mechanisms driving sepsis susceptibility in this high‑risk population remain unclear. Glucose‑regulated protein 78 (GRP78), the master regulator of endoplasmic reticulum stress, is aberrantly overexpressed and is involved in cell membrane translocation and extracellular release driven by the tumor microenvironment and anticancer therapies. To date, no clinical cohort study has directly established a causal link between GRP78 dysregulation and sepsis incidence or mortality in patients with cancer. The present narrative review therefore relied predominantly on indirect evidence from in vitro studies, animal models and non‑oncologic sepsis cohorts. Despite these limitations, the present study advanced the hypothesis that GRP78 dysregulation may increase sepsis susceptibility through two convergent mechanisms: i) Facilitating pathogen invasion via cell‑surface GRP78, which serves as a critical coreceptor for specific viruses and Mucorales fungi and ii) orchestrating immunosuppression through secreted GRP78‑mediated dampening of innate immune responses. Direct evidence for the function of cell‑surface GRP78 as a bacterial adhesion receptor is limited; its contribution to bacterial sepsis, the predominant clinical form, is primarily indirect and mediated by host inflammatory dysregulation, phagocytic impairment and barrier disruption. The present review provided a preliminary theoretical framework for future investigations into GRP78‑mediated sepsis susceptibility in patients with cancer, with hypothetical implications for risk stratification and targeted interventions, pending dedicated clinical validation in oncology‑specific cohorts.

The present study aimed to investigate the involvement of T‑box transcription factor 15 (TBX15) in the immune evasion by gastric cancer (GC) cells, as well as the molecular pathways that regulate TBX15 upstream and downstream. GC and paracancerous tissues were collected to verify the expression of TBX15, matrix metalloproteinase 14 (MMP14) and methyltransferase‑like 3 (METTL3) using reverse transcription‑quantitative PCR and western blotting. The co‑culture system of GC cell‑tumor‑associated macrophages (TAMs) and mouse forestomach carcinoma (MFC) cell‑CD8⁺ T cells was constructed. TBX15, MMP14 and METTL3 were highly expressed in GC tissues. Kaplan‑Meier analyses were performed, and high TBX15 expression predicted a poor prognosis for patients with GC. Silencing TBX15 promoted GC cell apoptosis and inhibited tumor development and the activity of proliferation, migration and invasion. TBX15 targeted the MMP14 promoter by using ChIP‑qPCR. Overexpression of MMP14 attenuated the reduction caused by TBX15 silencing. METTL3 targets TBX15 mRNA and regulates the m6A level of TBX15. TBX15 is associated with macrophage and CD8⁺ T cell infiltration. In the co‑culture system of GC‑TAM and MFC‑CD8⁺ T cells, TBX15 overexpression alleviated the decrease in M2 polarization and activation of CD8⁺ T cell antitumor activity caused by METTL3 silencing. However, MMP14 overexpression resulted in TBX15 silence‑induced decreases in M1 macrophage polarization and CD8⁺ T cell activity. These data suggested that TBX15, correlated with poor prognosis in patients with GC, promotes immune escape in GC cells. TBX15, regulated by m6A methylation, targeted the MMP14 promoter, thereby regulating MMP14 expression. The METTL3/TBX15/MMP14 signaling axis was involved in GC cell development, M2 macrophage polarization and CD8⁺ T cell antitumor activity activation. These findings provide a fundamental experimental rationale for TBX15 as a potential therapeutic target for GC.

The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified and studied in the regulation of glycogen synthesis. In some cases, suppression of GSK-3 activity by phosphorylation by Akt and other kinases has been associated with cancer progression. In these cases, GSK-3 has tumor suppressor functions. In other cases, GSK-3 has been associated with tumor progression by stabilizing components of the beta-catenin complex. In these situations, GSK-3 has oncogenic properties. The Raf kinase inhibitor protein (RKIP) has been reported to be under expressed in many cancers and plays a role in the regulation of tumor cells' survival, proliferation, invasion, and metastasis, hence, a tumor suppressor. RKIP also regulates tumor cell resistance to cytotoxic drugs/cells. Likewise, the tumor suppressor, phosphatase and tensin homolog (PTEN), which inhibits the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway, is either mutated, under expressed, or deleted in many cancers and shares with RKIP its anti-tumor properties and its regulation in resistance. Several pathways are regulated by RKIP, GSK-3, PTEN, and the transcriptional and post-transcriptional regulations of RKIP, GSK-3, and PTEN are significantly altered in cancers. In addition, RKIP, GSK-3 and PTEN play a key role in the regulation of tumor cells response to chemotherapy and immunotherapy. In this review, we will focus on the roles that GSK-3, PTEN, and RKIP play in various human cancers. We will also discuss how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mechanistic target of rapamycin complex 1 (mTORC1), nuclear Factor kappa-B (NF-κB)/Snail family transcriptional repressor 1 (Snail)/Yin Yang 1 (YY1) loop, and rat sarcoma virus oncogene (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK).

Environmental exposures are upstream determinants of molecular variation, yet exposure-to-biomarker gradients remain insufficiently quantified in harmonized multiomics cancer cohorts. Using TCGA lung adenocarcinoma as a model, we evaluated cumulative tobacco exposure and smoking history as determinants of variant-derived biomarkers and tested whether integrating clinical, genomic, transcriptomic, and proteomic data improves identification of high tumor mutational burden (TMB). This secondary analysis used public cBioPortal-linked TCGA data. Among 522 patients with clinical and molecular annotations, 302 ever-smokers with nonmissing pack-years, TMB, and covariates comprised the primary adjusted logistic-regression cohort, and 250 cases had matched multiomics data for prediction modeling. Higher cumulative tobacco exposure was associated with greater odds of high TMB: Compared with pack-year tertile 1, tertile 3 had an adjusted odds ratio of 2.28 (95% CI: 1.18, 4.41; p trend = 0.013), and each 10 pack-year increment was associated with an odds ratio of 1.12 (95% CI: 1.02, 1.23). Smoking categories also showed strong gradients for TMB, total nonsynonymous mutation counts, and C > A substitution fraction. Current smoking was positively associated with TP53 mutation and inversely associated with EGFR mutation relative to never-smoking. High-TMB tumors showed 201 differentially expressed transcripts and 15 differentially abundant proteins. Driver-augmented models discriminated high TMB better than broader multiomics models, although integrated scores retained prognostic relevance. These findings support exposure-aware biomarker development in lung adenocarcinoma. High TMB was defined as a cohort-specific top-quartile analytic endpoint rather than a universal clinical threshold. The findings support biomarker interpretation and hypothesis generation, not direct immunotherapy-response prediction or a clinically deployable model.

Colorectal cancer is recognized as one of the leading causes of cancer death amongst both sexes in the U.S. Despite rigorous screening, those diagnosed with colon cancer often face poor prognosis, and approximately 70% of affected patients will develop metastatic relapse. The investigation of colon carcinoma cell lines' genetic variability and response to chemotherapy panels may aid in targeting therapies to improve outcomes. This study aims to find correlations between metastasis status, gene variability, and drug response. We used two cell lines that were isolated from the same 51-year-old male with colorectal adenocarcinoma: a primary tumor-derived line (SW480) and a secondary metastasis-derived line (SW620). Live cell imaging using time-lapse microscopy over 3 days exhibited differential cell death responses following treatment with multiple chemotherapeutic agents, particularly cediranib and Nu-7441, with SW620 demonstrating greater sensitivity. Western blots revealed changes in DNA repair machinery expression (particularly NHEJ proteins) between SW480 and SW620. RNA sequencing and Gene Ontology analysis corroborated our findings, demonstrating upregulated DNA repair and metabolic survival genes including TGM2 in SW620 and PROM1 in SW480. An SW620 line grown in non-attachment plates and then reattached (SW620F) exhibited high DNA-PKcs activation and drug sensitivity. Correlation between drug response and gene expression crucial to cell growth and successful metastasis may reveal new biomarkers to target potential treatments.

Ablation technology is a key component of localised treatment strategies for solid tumours. Among these techniques, cryoablation is widely used in clinical practice because of its minimally invasive nature, controllability, and relatively low incidence of complications. A new generation of composite cryo-thermal ablation systems, independently developed in China, integrates cryoablation and thermal ablation, and its efficacy and safety have been extensively validated in clinical settings. Compared with traditional microwave ablation, radiofrequency ablation, or cryoablation alone, combined cryo-thermal ablation is more complex in terms of its therapeutic mechanisms, operational procedures, and risk management. This is particularly true in the pancreatic region, where delicate anatomical structures are located adjacent to vital vascular and ductal systems, significantly increasing the technical difficulty of treatment implementation. To standardise the application of image-guided combined cryo-thermal ablation for malignant pancreatic tumours, reduce procedural risks, and minimise the incidence of complications, experts from the Committee of Tumor Ablation, and the Chinese College of Interventionalists,the Committee of Ablation Therapy in Oncology, the Chinese Anti-Cancer Association, the Expert Committee on Ablation Therapy, the Chinese Society of Clinical Oncology (CSCO) have formulated this operational consensus. This consensus is based on a thorough review of the available evidence-based medical literature and domestic multi-centre clinical experience, with the aim of providing systematic technical guidance for clinical practice.

Colorectal cancer (CRC) is usually diagnosed when therapeutic options are limited, highlighting the need for novel molecular targeted therapies. MicroRNAs, as important regulators in cancer-related pathways, may provide therapeutic targets through their gene networks; however, the role of the miR-625-5p network in CRC remains unclear. Therefore, this study aimed to identify potential therapeutic targets in CRC through miR-625-5p-regulated network analysis.

miR-625 expression in TCGA samples was analyzed to assess its potential role in CRC development/progression. miR-625-5p targets were integrated from multiple resources to construct a protein-protein interaction network (PPIN) and identify clusters and key hub genes using Cytoscape. Key hub genes underwent enrichment analysis using DAVID and CancerHallmarks, followed by validation in independent CRC datasets from GEO and TCGA. Validated Key hub genes were further analyzed using TNMplot and Kaplan-Meier survival analysis to assess their expression patterns and prognostic significance, respectively. Druggability of the prognostic final hub gene was assessed using the Open Targets Platform.

miR-625 was significantly downregulated in CRC, particularly in advanced stages (p-value < 0.05). PPIN analysis of 755 target genes identified 24 key hub genes and four functional clusters. Enrichment analysis of key hub genes showed involvement in regulation of apoptotic processes, programmed cell death, and cancer-related pathways. Five candidate genes were validated in GEO and TCGA datasets; three were confirmed in TNMplot, and only HSP90AB1 was associated with poorer disease-free survival (p-value < 0.05) and exhibited druggable potential in CRC.

HSP90AB1 is a candidate therapeutic target in CRC.

Cancer progression is driven by the accumulation of DNA mutations and aberrant gene regulation. Recent studies have demonstrated that multiple H3 mutations serve as drivers of tumorigenesis. However, the role and significance of various cancer-associated histone H2B mutations in cancer development remain unknown. Here, we investigate H2BE113K, a missense mutation of histone H2B predominantly found in patients with breast cancer. We show that H2BE113K promotes colony formation in breast cancer. Notably, transcriptomic analysis reveals differential expression of genes in various cancer pathways in H2BE113K cells. The loci with elevated gene expression display increased chromatin accessibility, accompanied by H2BE113K enrichment. Depletion of G3BP2, one of the H2BE113K target genes that has been implicated in breast cancer, reduces the colony formation phenotype in H2BE113K cells. In addition, H2BE113K knock-in mice crossbred with an MMTV-PyMT breast cancer model show elevated lung metastasis. Together, our findings provide critical insights in the mechanistic role of H2BE113K in gene regulation, chromatin function, and breast cancer progression.

Vestibular schwannoma (VS) is a benign Schwann cell-derived tumor that frequently causes progressive hearing loss and vestibulocochlear dysfunction, substantially impacting quality of life. The molecular mechanisms underlying VS pathobiology remain poorly defined, and reliable biomarkers or targeted therapies are lacking. This study aimed to delineate the molecular landscape of VS through a transcriptome-wide meta-analysis. We performed a genome-wide random-effects meta-analysis of four independent Affymetrix microarray datasets from the Gene Expression Omnibus (GEO) database. Differential expression analyses were conducted with and without covariate adjustment. Gene Ontology enrichment and DrugBank-based drug-gene interaction analyses were subsequently applied to characterize biological pathways and assess translational potential. Across the meta-analysis, more than 3,200 differentially expressed genes were identified in the covariate-free model. After applying a more stringent threshold (|metaLFC| > 1 and FDR < 0.05), 1,095 genes remained differentially expressed, with high concordance between the covariate-free and covariate-adjusted models. Downregulated genes included extracellular matrix and stromal components (MFAP5, FABP4, DCN), and sensory- and synapse-related transcripts (SLC22A3, LGI1). Upregulated genes included immune- and inflammation-associated genes (TREM2, CCL3, CCL4, L1CAM) and proliferative regulators (CCND1, RAB31, MOXD1). Functional enrichment highlighted extracellular matrix remodeling, immune modulation, sensory signaling, and cell cycle pathways. Notably, many of the most strongly dysregulated genes have not previously been associated with VS. Drug-gene interaction analysis identified multiple dysregulated genes with known pharmacological targets, suggesting potential translational relevance. This transcriptome-wide meta-analysis provides a comprehensive overview of gene expression patterns in VS, highlighting alterations related to extracellular matrix organization, sensory and synaptic processes, immune-associated signaling, and cell cycle-related pathways. The study highlights novel disease-associated genes and pathways and may help prioritize candidates for further investigation, including those with potential relevance for therapeutic targeting.