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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Elucidating the role of tumor-associated ALOX5+ mast cells with transformative function in cervical cancer progression via single-cell RNA sequencing

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

Published: Aug. 19, 2024

Background Cervical cancer (CC) is the fourth most common malignancy among women globally and serves as main cause of cancer-related deaths in developing countries. The early symptoms CC are often not apparent, with diagnoses typically made at advanced stages, which lead to poor clinical prognoses. In recent years, numerous studies have shown that there a close relationship between mast cells (MCs) tumor development. However, research on role MCs played still very limited time. Thus, study conducted single-cell multi-omics analysis human cells, aiming explore mechanisms by interact microenvironment CC. goal was provide scientific basis for prevention, diagnosis, treatment CC, hope improving patients’ prognoses quality life. Method present acquired RNA sequencing data from ten samples ArrayExpress database. Slingshot AUCcell were utilized infer assess differentiation trajectory cell plasticity subpopulations. Differential expression subpopulations performed, employing Gene Ontology, gene set enrichment analysis, variation analysis. CellChat software package applied predict communication cells. Cellular functional experiments validated functionality TNFRSF12A HeLa Caski lines. Additionally, risk scoring model constructed evaluate differences features, prognosis, immune infiltration, checkpoint, across various scores. Copy number levels computed using inference copy variations. Result obtained 93,524 high-quality classified into types, including T_NK endothelial fibroblasts, smooth muscle epithelial B plasma MCs, neutrophils, myeloid Furthermore, total 1,392 subdivided seven subpopulations: C0 CTSG+ C1 CALR+ C2 ALOX5+ C3 ANXA2+ C4 MGP+ C5 IL32+ C6 ADGRL4+ MCs. Notably, subpopulation showed associations tumor-related results indicating resided intermediate-to-late stage differentiation, potentially representing crucial transition point benign-to-malignant transformation CNVscore bulk further confirmed transforming state subpopulation. revealed key receptor involved actions Moreover, vitro indicated downregulating may partially inhibit development prognosis infiltration based marker genes provided valuable guidance patient intervention strategies. Conclusions We first identified transformative tumor-associated within critical impacted progression inhibitory effect knocking down prognostic ALOX5+MCs subset demonstrated excellent predictive value. These findings offer fresh perspective decision-making

Language: Английский

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Multi-omics analysis and experimental validation of the value of monocyte-associated features in prostate cancer prognosis and immunotherapy

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

Published: June 14, 2024

Background Monocytes play a critical role in tumor initiation and progression, with their impact on prostate adenocarcinoma (PRAD) not yet fully understood. This study aimed to identify key monocyte-related genes elucidate mechanisms PRAD. Method Utilizing the TCGA-PRAD dataset, immune cell infiltration levels were assessed using CIBERSORT, correlation patient prognosis was analyzed. The WGCNA method pinpointed 14 crucial genes. A diagnostic model focused monocytes developed combination of machine learning algorithms, while prognostic created LASSO algorithm, both which validated. Random forest gradient boosting singled out CCNA2 as most significant gene related monocytes, its function further investigated through enrichment analysis. Mendelian randomization analysis association HLA-DR high-expressing Molecular docking employed assess binding affinity targeted drugs for PRAD, experimental validation confirmed expression value Result Based identification by WGCNA, we PRAD multiple algorithms. Additionally, constructed demonstrated excellent predictive capabilities. Analysis random algorithms supported potential Gene revealed regulation cycle cellular senescence that expressing high may promote results suggested strong targeting Furthermore, immunohistochemistry experiments validated upregulation prognosis. Conclusion Our findings offer new insights into monocyte heterogeneity holds novel drug

Language: Английский

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DEPDC1 as a metabolic target regulates glycolysis in renal cell carcinoma through AKT/mTOR/HIF1α pathway

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(7)

Published: July 27, 2024

Abstract Renal cell carcinoma (RCC) is considered a “metabolic disease” characterized by elevated glycolysis in patients with advanced RCC. Tyrosine kinase inhibitor (TKI) therapy currently an important treatment option for RCC, but drug resistance may develop some patients. Combining TKI targeted metabolic provide more effective approach An analysis of 14 RCC (including three needle biopsy samples resistance) revealed sing-cell RNA sequencing (scRNA-seq) that played crucial role poor prognosis and TCGA-KIRC gene set identified DEPDC1 as target associated malignant progression KIRC. Subsequent experiments demonstrated promoted knockdown could reverse lines. Bulk (RNA-seq) non-targeted metabolomics suggested regulate via AKT/mTOR/HIF1α pathway, finding supported protein-level analysis. Clinical tissue from 98 was predicted metastasis. In conclusion, this multi-omics suggests serve novel combined resistance.

Language: Английский

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Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM

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

Published: April 10, 2024

Skin Cutaneous Melanoma (SKCM) incidence is continually increasing, with chemotherapy and immunotherapy being among the most common cancer treatment modalities. This study aims to identify novel biomarkers for response in SKCM explore their association oxidative stress.

Language: Английский

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Molecular mechanisms and signaling pathways related to brain metastasis in breast cancer

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 27, 2025

Brain metastasis in breast cancer (BCBM) significantly threatens the survival and quality of life patients, particularly those with triple-negative (TNBC) HER2-positive subtypes. It involves complex molecular mechanisms diverse signaling pathways. This review highlights recent research on pathways BCBM. The process BCBM includes several key steps: local infiltration cells into bloodstream subsequent spread to brain. They must then overcome blood-brain barrier (BBB) establish grow Multiple pathways, including PI3K/AKT, STAT3, NF-κB, Notch, Wnt are involved this process. Overall, is a disease regulated by multiple To improve patient life, it crucial deepen explore new treatment targets strategies. will enhance our understanding lead more effective treatments.

Language: Английский

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Sesquiterpene lactones and cancer: new insight into antitumor and anti-inflammatory effects of parthenolide-derived Dimethylaminomicheliolide and Micheliolide

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 20, 2025

The isolation and application of biological macromolecules (BMMs) have become central in applied science today, with these compounds serving as anticancer, antimicrobial, anti-inflammatory agents. Parthenolide (PTL), a naturally occurring sesquiterpene lactone derived from Tanacetum parthenium (feverfew), is among the most important BMMs. PTL has been extensively studied for its anticancer properties, making it promising candidate further research drug development. This review summarizes effects derivatives, focus on Micheliolide (MCL) Dimethylaminomicheliolide (DMAMCL). These compounds, PTL, developed to overcome PTL's instability acidic basic conditions low solubility. We also explore their potential targeted combination therapies, providing comprehensive overview therapeutic mechanisms highlighting significance future cancer treatment strategies.

Language: Английский

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Mechanisms of tumor-associated macrophages in breast cancer and treatment strategy

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 28, 2025

Breast cancer (BC) is the most common in women and a leading cause of cancer-related mortality. Despite advances screening treatment, outcomes for advanced or recurrent BC remain poor, highlighting need new strategies. Recent research emphasizes tumor microenvironment (TME), particularly tumor-associated macrophages (TAMs), as key drivers growth, metastasis, resistance to therapy. The presence M2-like TAMs TME promotes immune evasion progression across subtypes. This review summarizes classification, their role BC, emerging therapies targeting TAMs, including depletion, inhibition recruitment, reprogramming from pro-tumoral M2 anti-tumoral M1 phenotypes. Targeting offers promising strategy improve treatment outcomes.

Language: Английский

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The role of Treg cells in colorectal cancer and the immunotherapy targeting Treg cells

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 16, 2025

Colorectal cancer (CRC) is among the most prevalent and lethal cancers globally, accounting for approximately 10% of all cases deaths. Regulatory T (Treg) cells, which accumulate in CRC tissue, suppress anti-tumor immune responses facilitate tumor progression. This review discusses Treg cell origins functions, along with mechanisms by Tregs influence development. In addition, we highlight therapeutic strategies targeting Tregs-such as checkpoint inhibitors combinatorial approaches-to enhance effector responses. A deeper understanding Treg-mediated immunosuppression may inform design more effective immunotherapies precision medicine strategies.

Language: Английский

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The Role of the p21-Activated Kinase Family in Tumor Immunity

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3885 - 3885

Published: April 20, 2025

The p21-activated kinases (PAKs) are a group of evolutionarily conserved serine/threonine protein and serve as downstream target the small GTPases Rac Cdc42, both which belong to Rho family. PAKs play pivotal roles in various physiological processes, including cytoskeletal rearrangement cellular signal transduction. Group II (PAK4-6) particularly closely linked human tumors, such breast pancreatic cancers, while I (PAK1-3) indispensable for normal functions cardiovascular development neurogenesis. In recent years, association with diseases like cancer rise small-molecule inhibitors targeting have attracted significant attention. This article focuses on analysis PAKs’ role tumor progression immune infiltration, well current their mechanisms.

Language: Английский

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