Luteolin, a bioactive compound from Celastrus orbiculatus stem, inhibits cervical cancer via CA2 suppression: A translational study bridging basic research and clinical application.

Hepatocellular carcinoma (HCC) is an aggressive liver malignancy, the molecular mechanisms underlying the progression of which are not fully understood. As a component of the chaperonin‑containing tailless complex polypeptide 1 (TCP1) ring complex, chaperonin‑containing TCP1 subunit 2 (CCT2) participates in the development of numerous types of liver disease. However, the potential role of CCT2 in regulating HCC malignant behaviors remains unclear. In the present study, bioinformatics analysis of patients with HCC from public datasets (The Cancer Genome Atlas‑Liver HCC, International Cancer Genome Consortium‑Liver Cancer‑Riken‑Japan and OEP00000321) demonstrated that CCT2 expression was upregulated in HCC tissue. High expression of CCT2 was also associated with an unfavorable overall survival prognosis. CCT2 knockdown was shown to inhibit the proliferation, migration, invasion and stemness and promote the apoptosis of HCC cells in vitro, as evidenced by EdU, colony formation, flow cytometry, caspase‑3/7 activity, gap closure, Transwell and tumor‑sphere formation assays. Consistently, knocking down CCT2 also suppressed the subcutaneous tumor proliferation and hematogenous lung metastasis of the human HCC HCCLM3 cells in vivo. Furthermore, downregulation of CCT2 decreased the phosphorylation of STAT3, as well as the expression of myeloid cell leukemia sequence 1, matrix metalloproteinase 2 and SRY‑box transcription factor 2 in vitro and in vivo. However, IL‑6 treatment rescued the levels of phosphorylated STAT3 and counteracted the inhibitory effects of CCT2 knockdown on proliferation and invasion. The findings suggest that CCT2 promotes HCC by activating the STAT3 signaling pathway. Therefore, CCT2 may serve as a survival biomarker and precision treatment target in HCC.

Identifying neurotrophic factor related genes at the crosstalk between glioblastoma and ischemic stroke.

Identification and validation of a pyroptosis-relevant model for the prognosis of cutaneous melanoma

PFHxS is predicted to bind KEAP1 and is associated with NRF2-NQO1 activation in hepatocellular carcinoma.

Gliomas are primary brain tumors known for their resistance to radiotherapy and frequent recurrence. This might result from the high heterogeneity and transcriptional plasticity of gliomas. Heat shock proteins are associated with unfavorable tumor outcomes and protect tumors from the effects of radiotherapy. However, their influence on brain tumors is not fully understood. Initial analyses of glioma patients from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases who had undergone radiotherapy identified HSP90B1 as a crucial gene affecting patient prognosis. Subsequent investigations revealed that HSP90B1 enhanced the proliferation, migration, and invasion of glioma cells. It was also found to protect glioma cells from radiotherapy-induced apoptosis. Co-immunoprecipitation (CO-IP) found that HSP90B1 directly interacted with RhoC and protected it from degradation via the ubiquitin-proteasome pathway. Rescue experiments indicated that HSP90B1 might facilitate glioma migration, invasion, and radiotherapy resistance by modulating RhoC expression. A mouse model further demonstrated that gliomas expressing high levels of HSP90B1 exhibited decreased sensitivity to radiotherapy. Overall, our research revealed that HSP90B1 significantly impacts the prognosis of glioma patients treated with radiotherapy. Additionally, HSP90B1 might enhance glioma metastasis and resistance to radiotherapy by regulating RhoC expression. This regulatory effect was achieved by the directly binding of HSP90B1 to RhoC, thereby preventing its degradation through the ubiquitin-proteasome pathway.

Molecular heterogeneity of endometrial cancer in the real-world: Biomarker patterns by tumor stage, histology, and molecular subtype.

The survival differences between splenic flexure cancer (SFC) and descending colon cancer (DCC) are unclear owing to their distinct anatomic and molecular features. This study compares their survival outcomes and genetic differences using data from the Surveillance, Epidemiology, and End Results (SEER) and The Cancer Genome Atlas (TCGA) databases. This study used SEER data (2000-2022) to compare postoperative patients with SFC and DCC. Propensity score matching (PSM) was performed to balance baseline characteristics. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method, and competing-risk analysis with a multivariable Fine-Gray model was used to evaluate cancer-specific death (CSD). TCGA transcriptomic data were analyzed to identify differentially expressed genes and enriched pathways between SFC and DCC. A total of 7579 patients were identified from SEER, including 2636 with SFC and 4943 with DCC. After PSM, DCC remained associated with significantly better OS and CSS than SFC. Competing-risk analysis showed that SFC had higher cumulative incidences of both CSD and other-cause death, and multivariable Fine-Gray analysis further demonstrated that DCC was independently associated with a lower risk of CSD than SFC (subdistribution hazard ratio, 0.73; P =.019). Younger age and adequate nodal evaluation were protective, whereas advanced tumor burden, particularly T4 and N2 disease, remained strongly adverse. TCGA analysis further demonstrated distinct transcriptional profiles between the 2 subsites, with SNHG4 upregulated and AHCYL2 downregulated in SFC, alongside subsite-associated differences in fatty-acid metabolism, spliceosome-related signaling, and ribosome-associated processes. SFC is associated with worse survival than DCC, and transcriptomic profiles are distinct between the 2 subsites in TCGA.

The YTH domain family protein 1 (YTHDF1), a key N1-methyladenosine (m1A) modification reader protein, has been significantly associated with the proliferation and invasion of various malignant cells. However, knowledge of the precise role of YTHDF1 in hepatocellular carcinoma (HCC) and the molecular mechanisms involving RNA m1A modification remains incomplete. This study integrated HCC data from The Cancer Genome Atlas (TCGA), tissue microarray (TMA), in vitro functional experiments, and in vivo xenograft models to explore the regulatory role of YTHDF1-mediated RNA m1A modification in HCC. Bioinformation analysis and TMA revealed that YTHDF1 expression is significantly upregulated in HCC tissues and correlated with poor prognosis of HCC patients. Functional experiments demonstrated that YTHDF1 knockdown markedly suppresses the proliferation and invasion of HCC cells, which was further confirmed by in vivo xenograft models. Integrated m1A methylated RNA immunoprecipitation sequencing (MeRIP-seq), MeRIP-qPCR, transcriptome-sequencing (RNA-seq) and RNA immunoprecipitation-qPCR (RIP-qPCR) showed the distribution change of m1A modifications after YTHDF1 knockdown, identified LRP5 as the downstream target of YTHDF1, and confirmed the direct binding of YTHDF1 to LRP5 mRNA. The Actinomycin D and dual-luciferase reporter assays confirmed that YTHDF1 can affect the stability of LRP5 mRNA. Further in vitro experiments indicated that YTHDF1 knockdown reduces the protein levels of key Wnt pathway components and inhibits the cell malignant phenotype, while LRP5 overexpression reverses the effects induced by YTHDF1 knockdown. In conclusion, YTHDF1-mediated RNA m1A modifications facilitate the malignant progression of HCC by modulating the LRP5/Wnt/β-catenin signaling pathway.

Endometrial cancer (EC) is a one of the most prevalent gynecological malignancies worldwide; however, the molecular mechanisms driving its progression remain insufficiently understood. In the present study, DNA polymerase θ (POLQ), which is implicated in multiple types of cancer, was comprehensively investigated in EC using data from The Cancer Genome Atlas and TNMplot datasets, with further validation in an independent patient cohort. POLQ expression was markedly upregulated in EC tissues and was associated with reduced 15‑year overall survival. Increased POLQ levels were also associated with higher Ki67 proliferation indices, distinct patterns of T‑cell infiltration and enhanced programmed death‑ligand 1 (PD‑L1) expression. Gene Set Enrichment Analysis revealed that POLQ expression was associated with pathways involved in cell proliferation, cell cycle regulation and DNA damage repair. Mechanistic studies based on POLQ knockdown in EC cells were conducted in vitro using small interfering RNA‑mediated gene silencing, followed by functional assays including cell proliferation assay, flow cytometric cell cycle analysis, apoptosis assay, migration and invasion assays, and western blot analysis to detect the expression of key proteins involved in ATM/P53 signaling and epithelial‑mesenchymal transition (EMT) regulation. These experiments further demonstrated that POLQ may accelerate EC progression via two complementary mechanisms: i) Activation of ataxia‑telangiectasia mutated/P53 signaling to facilitate cell cycle checkpoint bypass; and ii) induction of EMT via cadherin switching. Collectively, these findings established POLQ as a robust prognostic biomarker and a promising therapeutic target in EC.

Pleural mesothelioma (PM) is a rare and aggressive malignancy. The development of novel therapeutic strategies targeting PM remains an unmet clinical need. However, comprehensive genomic data from Asian populations, particularly from Japanese patients, are limited. This study aimed to elucidate the genomic landscape of PM in Japanese patients using the nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) genomic database. A total of 211 patients registered between June 2019 and March 2025 were analyzed. The most frequent genetic alterations were in BAP1, NF2, TP53, CDKN2A/B, and MTAP. The median tumor mutation burden (TMB) was 1.26, and no microsatellite instability-high patients were detected. The median overall survival (OS) after first-line treatment was 30.6 months. Patients treated with immune checkpoint inhibitors (ICIs) had a significantly better OS than those who did not receive ICIs. In univariate and multivariate analyses, TP53 alterations and high TMB (cutoff value of 1.6) were associated with poor prognosis. These results suggest that integrating clinical and genomic data can enhance prognostic stratification and contribute to the development of precision medicine for PM. This study provides the first large-scale genomic characterization of Japanese PM patients with C-CAT and highlights potential biomarkers for future therapeutic development.

Identifying cancer driver genes (CDGs) remains a central challenge in cancer genomics, as frequency-based mutation approaches often miss rare but functionally important regulators. We present PICDGI, a computational framework that predicts driver-like regulatory genes by integrating dynamic gene-gene interaction modeling with single-cell RNA sequencing (scRNA-seq) data. Rather than relying on DNA mutation calls, PICDGI infers functional driver activity from time-resolved expression patterns and latent regulatory influence among genes during tumor progression. Methodologically, PICDGI employs a time-varying state-space model with variational Bayesian inference and Markov Chain Monte Carlo (MCMC) sampling to estimate evolving gene interaction effects. The posterior distributions capture both the magnitude and uncertainty of each gene’s inferred regulatory influence. From these, PICDGI derives a driver coefficient that quantifies the strength and reliability of each gene’s contribution to progression-associated expression dynamics, enabling the prioritization of impactful regulators over neutral passengers. Applied to lung adenocarcinoma (LUAD) scRNA-seq data, PICDGI recovered known oncogenes and tumor suppressors and nominated novel candidate drivers, including JPH1 and CHEK1 , which are implicated in calcium signaling, mitochondrial regulation, and DNA repair. These genes exhibit trajectory-aligned activity consistent with tumor evolution and immune-modulatory processes. Comparative analysis using Moran’s I statistics in Monocle 3 showed that PICDGI-prioritized genes display stronger progression-associated dynamics than genes selected by spatial autocorrelation alone. We further validated PICDGI on an independent pediatric acute myeloid leukemia (AML) scRNA-seq cohort, where it consistently recovered known drivers and relapse-associated regulatory programs under fixed model parameters. By integrating interaction-informed dynamic modeling with single-cell resolution data, PICDGI provides a generalizable and biologically grounded framework for identifying rare and context-specific regulatory drivers of cancer progression, with broad applicability across tumor types.

Introduction The accurate detection of somatic Copy Number Variations (CNVs) is a challenging task in cancer genomics. This study addresses the significant variability in performance and the lack of consensus among computational tools for somatic CNV calling. Methods We conducted a comprehensive benchmark evaluation of four widely used tools - CNVkit, Sequenza, Facets, and ASCAT. Their performance was assessed in terms of recall, precision, reproducibility, and inter-tool concordance using an orthogonally validated real-world dataset derived from the HCC1395 cell line. Results Our analysis revealed considerable differences in tool performance. Facets and Sequenza showed the most balanced accuracy and the highest reproducibility. In contrast, we observed poor consensus among tools, particularly for amplifications, where pairwise concordance values were frequently below 0.6. CNVkit showed high sensitivity for deletions but exhibited critically low and unstable performance for amplifications. Discussion The results show that tool selection is a primary source of variability in CNV studies, which can significantly impact downstream biological interpretation. The high discordance rates, especially for amplifications, highlight the inherent limitations and the risk of false negatives when relying on a single algorithm. Conclusion We conclude that for reliable somatic CNV detection, tools such as Facets or Sequenza are required. We also recommend adopting a consensus-based approach to reduce error rates and improve the quality of findings from individual algorithms.

INTRODUCTION: Hepatocellular carcinoma (HCC) is associated with poor clinical outcomes, underscoring the need to identify novel biomarkers and therapeutic targets. PFKP, a key rate-limiting enzyme in glycolysis, is involved in tumor metabolic reprogramming, but its role in HCC prognosis, immune regulation, and therapeutic responsiveness remains incompletely understood. METHODS: We combined transcriptomic profiles and clinical information from The Cancer Genome Atlas (TCGA) with analyses of clinical HCC specimens. PFKP expression, survival associations, functional enrichment, and tumor immune microenvironment characteristics were systematically evaluated. Drug sensitivity was predicted using data from the GDSC database. Validation was performed by immunohistochemistry (IHC) in patient samples and by Western blotting in PFKP-overexpressing HepG2 cells treated with or without the glycolysis inhibitor 2-deoxy-D-glucose (2-DG). RESULTS: PFKP expression was markedly increased in HCC and was independently associated with unfavorable survival. Elevated PFKP levels were linked to an immunoregulatory microenvironment and increased expression of immune checkpoint molecules (PD-L1, CTLA-4), which was confirmed by IHC. High PFKP expression was also associated with predicted greater responsiveness to immune checkpoint blockade and distinct drug sensitivity profiles. Mechanistically, PFKP overexpression increased the expression of key glycolytic enzymes, enhanced PD-L1 expression, and was accompanied by activation of mTOR-related signaling, whereas these effects were attenuated by glycolytic inhibition. DISCUSSION: PFKP is a critical link between glycolysis and immune suppression in HCC. It promotes immune checkpoint expression and mTOR activation, suggesting a role in immune evasion. PFKP represents a dual biomarker for prognosis and immunotherapy response, and a promising target for combined metabolic and immune-based therapies.

The high toxicity of current therapies and frequent relapse in mature B-cell non-Hodgkin lymphomas (B-NHLs) reveal a substantial unmet clinical need for more effective targeted treatment strategies. To address this gap, Gene Set Enrichment Analysis (GSEA) of B-NHL datasets was conducted, uncovering markedenrichment of E2F transcription factors and their target genes. Despite the central role of E2F signaling in cell cycle control and oncogenesis, its contribution to pediatric B-NHLs has not been systematically characterized. Accordingly, we performed a comprehensive analysis of E2F signaling and its downstream targets to identify potential therapeutic and prognostic biomarkers in pediatric B-NHLs. The datasets used for this analysis were obtained from the Gene Expression Omnibus (GEO) database, and mRNA and protein expression levels were further validated via data from The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). Key bioinformatics findings were validated via quantitative PCR (qPCR) and cell proliferation assays. Survival analysis was conducted to evaluate the associations between gene expression levels and the prognosis of B-NHL patients. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA were employed to predict gene functions and associated pathways. Childhood B-NHLs were markedly enriched for E2F gene set. The identified overlapping differentially expressed genes (DEGs) were linked to cell cycle regulation, DNA replication, and proliferative activity. E2F1 and hub genes such as POLD1, LIG1, MCM3, MCM6, and PCNA were markedly overexpressed in B-cell lymphoma. These genes demonstrated strong discriminatory potential as disease-associated signaling molecules. Moreover, the expression of POLD1 was closely associated with the proliferative capacity of B-NHLs. E2Fs and their downstream target genes are significantly overexpressed in pediatric B-NHLs, driving tumor cell proliferation. These molecules may serve as biomarkers for therapeutic stratification, prognosis, and disease monitoring in pediatric B-NHLs.

Tobacco use is associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). Bitter taste receptor (T2R) activation induces apoptosis via calcium-dependent signaling, and higher T2R expression correlates with increased survival in HNSCC. However, the effects of cigarette smoke on T2R signaling remain unclear. HNSCC cell lines were treated with cigarette smoke condensate (CSC). T2R expression was measured by qPCR, and function evaluated by calcium imaging, viability, and apoptosis assays following stimulation with denatonium benzoate and flufenamic acid. T2R expression was also assessed in patient-derived tumor tissue and The Cancer Genome Atlas (TCGA). CSC reduced T2R expression, impaired calcium signaling, and diminished T2R-mediated apoptosis, particularly in SCC47 cells. Lower expression was observed in CSC-exposed patient-derived tumor tissue and TCGA tumors from smokers versus nonsmokers. Cigarette smoke disrupts T2R signaling and reduces apoptosis in HNSCC, suggesting a mechanism by which ongoing tobacco use may alter tumor biology and treatment response.

The MAPRE3 gene is aberrantly expressed in several cancers. We profiled DNA methylation in tumor tissues from early-stage non-small cell lung cancer (NSCLC) patients and assessed associations with overall survival (OS). Significant CpG probes were validated in The Cancer Genome Atlas (TCGA). The methylation level of cg12821679MAPRE3 showed significant associations with OS in lung squamous cell carcinoma (LUSC) (HR = 0.32, P = 6.55 × 10-7), but it was not observed in lung adenocarcinoma (LUAD). In LUSC, MAPRE3 expression was significantly correlated with cg12821679MAPRE3 (r = 0.17, P = 2.96 × 10-3) and potential trans-regulated genes were enriched in the Nicotine addiction pathway. Additionally, MAPRE3 expression showed significant associations with OS in both LUAD and LUSC (LUAD: HRlow vs high = 2.28, P = 2.40 × 10-3; LUSC: HRlow vs high = 1.61, P = 0.0244). The association between smoking cessation and overall survival was significantly modified by MAPRE3 expression (HRinteraction = 0.69, P = 0.0282). Smoking cessation improved OS only in patients with high MAPRE3 expression (HR = 0.56, P = 2.82 × 10-3). We conclude MAPRE3 may predict NSCLC prognosis and influence the prognostic benefit of smoking cessation.

Hepatocellular carcinoma (HCC) and major depressive disorder (MDD) are characterized by shared pathophysiological mechanisms. However, the specific molecular indicators and the fundamental biological pathways driving this connection have yet to be fully elucidated. This study aims to identify immune-related molecular signatures shared by HCC and MDD using a systems biology approach and to evaluate their potential prognostic and immune-related relevance. By integrating MDD transcriptomic data from the Gene Expression Omnibus with HCC transcriptomic and clinical data from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma repository, we performed weighted gene co-expression network analysis, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes functional enrichment, Gene Set Enrichment Analysis, and least absolute shrinkage and selection operator-Cox regression to construct a prognostic model. The model was internally evaluated using survival analysis and time-dependent receiver operating characteristic analyses. Furthermore, to quantify the relative abundance of tumor-infiltrating immune cells and verify target mRNA levels, the CIBERSORT algorithm and quantitative reverse transcription polymerase chain reaction assays were implemented, respectively. Among the differentially expressed genes, NIN was identified as a candidate immune-related biomarker associated with HCC and MDD in separate transcriptomic analyses and validation cohorts, offering a crucial target for future research and potential development of early diagnostic tools and therapeutic strategies for this patient population.

Endometrial cancer is one of the most common gynecological malignancies, and advanced disease remains associated with poor clinical outcomes. Mucin 16 (MUC16), a transmembrane glycoprotein frequently mutated in multiple cancers, has been implicated in tumor progression. However, its functional role and molecular mechanism in endometrial cancer remain unclear. Somatic mutation data from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) were analyzed to evaluate the association between MUC16 mutation and tumor mutation burden (TMB). Functional assays were performed in endometrial cancer cell lines. Protein interactions and ubiquitination were examined using co-immunoprecipitation and ubiquitination assays. Xenograft mouse models and drug sensitivity assays were used to evaluate tumor growth and response to targeted therapy. MUC16 is frequently mutated in endometrial cancer and its mutation status is associated with increased tumor mutation burden and improved overall survival in endometrial cancer patients. Functional experiments further demonstrated that MUC16 protein expression promotes tumor cell proliferation, migration, and invasion. Mechanistically, MUC16 interacted with estrogen receptor 1 (ESR1) and enhanced its stability by inhibiting ubiquitin-mediated degradation, thereby activating the PI3K/AKT signaling pathway. In addition, MUC16 knockdown significantly increased the sensitivity of endometrial cancer cells to the targeted drug lapatinib. These findings reveal that MUC16 promotes endometrial cancer progression through the ESR1/PI3K/AKT axis and highlight MUC16 as a potential prognostic biomarker and therapeutic target.

Early onset colorectal cancer (EoCRC), commonly defined as colorectal cancer diagnosed in people under 50 years of age, is increasing in incidence in Australia and New Zealand. The underlying cause of this remains unclear, despite its growing public health importance. The objective of this scoping review was to comprehensively map and synthesise the literature for EoCRC across Australia and New Zealand, focusing on themes and data sources. A scoping review was performed according to the PRISMA guidance. English language, humans, publications 01/01/2000-31/05/2025, Australian and/or New Zealand patients, studies addressing EoCRC (adenocarcinoma). A systematic literature review was performed: 698 titles and abstracts were screened, 72 full texts were reviewed, with 59 studies included for final analysis. Studies were mostly derived from national and state-based cancer registries and thus presented results achievable by analysis of these databases: incidence, patient demographics, familial cancer syndromes and genetics, tumour characteristics, treatment, short term outcomes and survival. Direct comparison between studies was difficult due to the heterogeneity of patient groups and outcome measures. Gaps identified in the literature included lack of longitudinal risk factor analysis and detailed clinicopathological data. Australia and New Zealand benefit from the mandatory reporting of colon cancer into central registries. To further progress our understanding of EoCRC, prospectively collected and detailed clinicopathological data are required. Despite relatively small populations, the incidence of colorectal cancer in Australia and New Zealand remains among the highest in the world; insights obtained locally have potential global impact.