Evaluating the predictive value of angiogenesis-related genes for prognosis and immunotherapy response in prostate adenocarcinoma using machine learning and experimental approaches

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 16, 2024

Background Angiogenesis, the process of forming new blood vessels from pre-existing ones, plays a crucial role in development and advancement cancer. Although blocking angiogenesis has shown success treating different types solid tumors, its relevance prostate adenocarcinoma (PRAD) not been thoroughly investigated. Method This study utilized WGCNA method to identify angiogenesis-related genes assessed their diagnostic prognostic value patients with PRAD through cluster analysis. A model was constructed using multiple machine learning techniques, while developed employing LASSO algorithm, underscoring PRAD. Further analysis identified MAP7D3 as most significant gene among multivariate Cox regression various algorithms. The also investigated correlation between immune infiltration well drug sensitivity Molecular docking conducted assess binding affinity angiogenic drugs. Immunohistochemistry 60 tissue samples confirmed expression MAP7D3. Result Overall, 10 key demonstrated potential immune-related implications patients. is found be closely associated prognosis response immunotherapy. Through molecular studies, it revealed that exhibits high Furthermore, experimental data upregulation PRAD, correlating poorer prognosis. Conclusion Our important target

Language: Английский

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Pan-cancer analysis of CHRDL1 expression and its mechanistic role in inhibiting EMT via the TGF-β pathway in lung adenocarcinoma

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 31, 2025

The primary objective of this study is to conduct a pan-cancer analysis CHRDL1 expression, determine its correlation with patient survival rates, immune cell infiltration, and drug sensitivity. Additionally, the aimed further validate mechanistic role in lung adenocarcinoma (LUAD), clarifying contribution tumorigenesis evaluating potential as therapeutic target for LUAD. We employed bioinformatics strategies analyze expression using data from Cancer Genome Atlas (TCGA) Genotype-Tissue Expression Project (GTEx). Survival was executed GEPIA2, while sensitivity chemotherapeutic agents evaluated via CellMiner database. Mutational profiles were examined cBioPortal, microenvironment assessed through TIMER To substantiate our findings, we conducted vitro cellular assays vivo animal models actions levels showed significant variation across different cancer types, tumor tissues typically demonstrating lower compared their normal counterparts. In certain cancers, elevated linked poorer outcomes, whereas LUAD, it associated improved survival. Furthermore, correlated IC50 values multiple drugs played modulating microenvironment. discovered that inhibits epithelial-mesenchymal transition (EMT) LUAD TGF-β pathway. exerts complex influence on development progression, particularly by impacting regulation, chemosensitivity, EMT regulation. This research offers valuable insights into overarching mechanisms progression aids discovery innovative treatment.

Language: Английский

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EFTUD2 is a promising diagnostic and prognostic indicator involved in the tumor immune microenvironment and glycolysis of lung adenocarcinoma

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 1, 2025

Elongation Factor Tu GTP Binding Domain Containing 2 (EFTUD2), a conserved spliceosomal GTPase, is involved in craniofacial development and various cancers, but its role lung adenocarcinoma (LUAD) remains unclear. EFTUD2 expression LUAD tissues was analyzed using data from TCGA GEO, validated by immunohistochemistry, RT-qPCR, Western blotting. The relationship between clinical features examined Fisher's exact test. Diagnostic prognostic analyses were performed R. Hub genes related to identified through topological algorithms, immune infiltration assessed CIBERSORT. cGAS-STING pathway m6A modification also the cohort. Functional assays conducted assess EFTUD2's impact on cell proliferation, cycle, invasion, metastasis, while glycolytic enzyme levels measured upregulated cells, correlating with N classification, visceral pleural intravascular tumor embolism, cytokeratin-19 fragment antigen 21-1. Sixteen EFTUD2-related hub identified. Higher linked altered infiltration, increased TumorPurity scores decreased StromalScore, ImmuneScore, ESTIMATEScore values. Gene enrichment highlighted involvement adhesion, response. strongly associated modification. knockdown inhibited migration, tumorigenicity, causing G0/G1 phase cycle arrest, expression. These findings may suggest that positively regulates progression of modulates activity making it valuable for treatment prognosis. potential diagnostic marker LUAD, microenvironment, pathway, modification, glycolysis.

Language: Английский

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BMP signalling in colorectal cancer: losing the yin to WNTs yang

The Journal of Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Abstract Colorectal cancer (CRC) is the third most common form of globally, and arises from hyperproliferation epithelial cells in intestine. The architecture maintenance these governed by two major signalling pathways working a counter‐gradient: stem cell WNT pathway, prodifferentiation bone morphogenetic protein (BMP) pathway. It has long been known that this WNT‐BMP balance disrupted CRC, with hyperactive leading to increased proliferation tumour progression. BMP signalling, its effects, have increasingly become focus for CRC research. Loss receptors, shown increase CRC. further modulated through secreted antagonists localised intestinal crypts, which create niche ensuring sustained can maintain stem‐cell self‐renewal capacity. A number studies combine demonstrate effects overexpression antagonists, showing hyperactivity stem‐cell‐supporting pathway ensues, deregulation epithelium. Cellular hyperproliferation, emergence ectopic an numbers characteristics are themes, contributing homeostasis, risk progression, resistance therapy. This review aims compile current knowledge on their role development, how we utilise information biomarker research novel therapeutics. © 2025 Author(s). Journal Pathology published John Wiley & Sons Ltd behalf Pathological Society Great Britain Ireland.

Language: Английский

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A Comparative Study on Copy Number Variation in Subtypes of Breast Phyllodes Tumors

Breast Cancer Basic and Clinical Research, Journal Year: 2025, Volume and Issue: 19

Published: April 1, 2025

Background: Breast phyllodes tumor (PT) is a biphasic and constitutes about 0.3% to 1% of all breast tumors. The PT histologically classified as benign, borderline, malignant subtypes. Unlike epithelial cancers, derived from fibroepithelial tissues, the genomic information subtypes still limited. Objectives: objectives were gain deeper understanding changes in progression PTs benign borderline malignant. Design: In this study, we used an Affymetrix OncoScan Array analyze genome-wide copy number variations (CNVs) nucleotide point mutations 3 PTs, collected First Affiliated Hospital Zhengzhou University. Methods: DNA was extracted formalin-fixed paraffin-embedded (FFPE) specimens using TIANamp FFPE Kit. profiled for CNV analyzed Nexus Express Chromosome Analysis Suite. Results: Our silico variation analysis indicated loss Xp11.22 q22.1 (χ 2 = 9, P .0027) 22q11.23 Xq23 12, .0005). A observed 1p13.3 7p11.2 .0027). We also found consistent heterozygosity (LOH) 32 loci 23 PTs. Among 87 LOH, there 15 overlapping across missense NRAS , KRAS IDH2 TP53 frameshift deletion PTEN sequenced samples, irrespective their subtype. Interestingly, mutation EGFR/EGFR-AS1 only Conclusions: data suggested that at 7p11.2, 22q11.23, together with EGFR / EGFR-AS1 uniquely presented may correlate

Language: Английский

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Comprehensive pan-cancer analysis of CHRDL1 and experimental validation of its role in lung adenocarcinoma

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 26, 2025

Chordin-like 1 (CHRDL1) is a secreted antagonist of bone morphogenetic proteins, and has been implicated in various biological processes cancer prognosis. This study offered detailed examination CHRDL1 expression across 33 diverse types, leveraging data from The Cancer Genome Atlas (TCGA) supplementary public datasets. We demonstrated that, for the majority was reduced tumor tissues compared to normal adjacent tissues. Notably, lower led negative prognosis malignancies such as lung adenocarcinoma (LUAD), melanoma (SKCM), mesothelioma (MESO). Furthermore, positively correlated with infiltration CD4⁺ T cells, CD8⁺ B neutrophils, macrophages, dendritic cells most tumors. Higher more favorable immune profiles reduction stemness. To assess effect overexpression on LUAD progression, we conducted CCK-8, wound healing, invasion assays vitro, along subcutaneous formation experiments nude mice. results showed that proliferation, migration, abilities A549 H1299 high were reduced, growth also significantly inhibited These findings underscored CHRDL1's potential prognostic biomarker its influence immunology cellular dynamics.

Language: Английский

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Comprehensive analysis of the value of angiogenesis and stemness‐related genes in the prognosis and immunotherapy of ovarian cancer

BioFactors, Journal Year: 2024, Volume and Issue: 51(1)

Published: Dec. 20, 2024

Abstract Tumor angiogenesis and the presence of cancer stem cells (CSCs) are critical characteristics tumors. Previous research has demonstrated that promote tumor angiogenesis, while increased vascularity, in turn, fosters growth cells. This creates a detrimental cycle contributes to progression. However, studies investigating stemness ovarian (OV) limited. In this study, we employed cluster analysis LASSO methods assess significance angiogenesis‐ stemness‐related genes efficacy OV immunotherapy. Through multivariate Cox regression Friends analysis, identified TNFSF11 as most significant prognostic gene associated with stemness. Additionally, molecular docking results confirmed exhibits high affinity for sorafenib sunitinib. summary, first time, conducted comprehensive roles prognosis immunotherapy patients, revealing novel therapeutic target.

Language: Английский

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