Frontiers in Pharmacology, Год журнала: 2024, Номер 14
Опубликована: Янв. 12, 2024
Hepatocellular carcinoma (HCC) is responsible for approximately 90% of liver malignancies and the third most common cause cancer-related mortality worldwide. However, role anoikis, a programmed cell death mechanism crucial maintaining tissue equilibrium, not yet fully understood in context HCC.
Язык: Английский
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Фев. 10, 2024
Abstract Bladder cancer ranks as the 10th most common worldwide, with deteriorating prognosis disease advances. While immune checkpoint inhibitors (ICIs) have shown promise in clinical therapy both operable and advanced bladder cancer, identifying patients who will respond is challenging. Anoikis, a specialized form of cell death that occurs when cells detach from extracellular matrix, closely linked to tumor progression. Here, we aimed explore anoikis-based biomarkers for immunotherapeutic decisions. Through consensus clustering, categorized TCGA-BLCA cohort into two clusters based on anoikis-related genes (ARGs). Significant differences survival outcome, features, environment (TIME), potential ICIs response were observed between clusters. We then formulated four-gene signature, termed "Ascore", encapsulate this gene expression pattern. The Ascore was found be associated outcome served an independent prognosticator IMvigor210 cohort. It also demonstrated superior predictive capacity (AUC = 0.717) immunotherapy compared like TMB PD-L1. Finally, evaluated Ascore’s prognostic performance non-invasive biomarker our (Gulou-Cohort1) using circulating detection, achieving AUC 0.803. Another (Gulou-Cohort2) consisted 40 undergoing neoadjuvant anti-PD-1 treatment examined. Immunohistochemistry these revealed its correlation pathological ( P 0.004). Impressively, 0.913) surpassed PD-L1 0.662) forecasting indicated better net benefit. In conclusion, study introduces novel, robust offering new tool enhancing decisions contributing tailored approaches field.
Язык: Английский
Процитировано
16
Journal of Cancer, Год журнала: 2025, Номер 16(4), С. 1078 - 1100
Опубликована: Янв. 6, 2025
Anoikis resistance and improper activation of epithelial‒mesenchymal transition (EMT) are critical factors in tumor metastasis progression. Despite their interaction, the combined impact anoikis EMT on prognosis immunotherapy gastric cancer remains underexplored. In this study, we identified 354 anoikis- EMT-related genes (AERGs) through Venn analysis performed unsupervised clustering to classify patients into two molecular clusters: A B. Molecular cluster showed poor an immunosuppressive microenvironment, suggesting a "cold tumor" phenotype. Then, novel AERG-related prognostic model comprising CD24, CRYAB, MMP11, MUC4, PRKAA2, SERPINE1, SKP2, TP53 was constructed validated, accurately predicting 1-, 3-, 5-year survival rates patients. Multivariate revealed that risk score independent factor (hazard ratio = 1.651, 95% confidence interval 1.429-1.907, P<0.001). Further studies demonstrated that, compared high-risk group, low-risk group exhibited higher CD8+ T cell infiltration, mutational burden, immunophenoscores, lower immune dysfunction exclusion scores, indicating potential sensitivity immunotherapy. RT‒qPCR immunohistochemical staining validated expression levels model's markers. Overall, our shows promise for outcomes guiding selection tailored precise therapies
Язык: Английский
Процитировано
3
Thoracic Cancer, Год журнала: 2022, Номер 14(3), С. 320 - 330
Опубликована: Дек. 11, 2022
Abstract Background Lung adenocarcinoma (LUAD) is the most prevalent histotype of non‐small cell lung cancer. Anoikis, an alternative form programmed death, plays a pivotal role in cancer invasion and metastasis, preventing detached cells from readhering to other substrates for abnormal proliferation. The aim this study was conduct comprehensive analyses prognostic implications anoikis‐related genes (ARGs) LUAD. Methods ARGs were selected Cancer Genome Atlas (TCGA) database Genecards dataset using differential expression analysis. signature incorporating identified univariate Cox regression analysis LASSO Furthermore, nomogram containing clinical information developed through multivariate Kaplan–Meier survival receiver operating characteristic (ROC) curves applied evaluate predictive validity these risk models. Finally, functional immune landscape also conducted. Results A 16‐gene integrated stratify LUAD patients into different groups. score generated TNM stage as independent factors utilized develop nomogram. Both showed satisfactory prediction performance predicting overall (OS) patients. enriched several biological functions signaling pathways. differences investigated among high‐ low‐risk groups stratified by signature. Conclusions This revealed potential relationships between prognosis predictors present could be biomarkers applications.
Язык: Английский
Процитировано
39
MedComm, Год журнала: 2024, Номер 5(10)
Опубликована: Сен. 15, 2024
The extracellular matrix (ECM) governs a wide spectrum of cellular fate processes, with particular emphasis on anoikis, an integrin-dependent form cell death. Currently, anoikis is defined as intrinsic apoptosis. In contrast to traditional apoptosis and necroptosis, integrin correlates ECM signaling intracellular cascades, describing the full process anoikis. However, frequently overlooked in physiological pathological processes well vitro research models. this review, we summarized role spanning embryonic development, organ tissue repair, inflammatory responses, cardiovascular diseases, tumor metastasis, so on. Similarly, realm stem focused functional evolution cells, offers potential solution various challenges, including culture models, therapy, transplantation, engineering applications, which are largely based regulation by More importantly, regulatory mechanisms molecular will provide new strategies for therapeutic interventions (drug therapy cell-based therapy) disease. summary, review provides systematic elaboration thus shedding light its future research.
Язык: Английский
Процитировано
7
Frontiers in Pharmacology, Год журнала: 2023, Номер 13
Опубликована: Янв. 4, 2023
Background: Hepatocellular carcinoma (HCC) is a common malignancy with high mortality worldwide. Despite advancements in diagnosis and treatment recent years, there still an urgent unmet need to explore the underlying mechanisms novel prognostic markers. Anoikis has received considerable attention because of its involvement progression human malignancies. However, potential mechanism anoikis-related genes (ANRGs) HCC remains unclear. Methods: We use comprehensive bioinformatics analyses determine expression profile ANRGs their implications HCC. Next, risk score model was established by least absolute shrinkage selection operator (Lasso) Cox regression analysis. Then, value correlation clinical characteristics patients were further explored. Additionally, machine learning utilized identify outstanding score. Finally, protein DAP3 examined on tissue microarray (TMA), Results: dysregulated HCC, low frequency somatic mutations associated prognosis patients. nine selected construct signature based LASSO model. The presented strong ability stratification prediction for overall survival patients.Additionally, scores closely correlated unfavorable features such as advanced pathological stage, poor histological differentiation vascular invasion. Moreover, XGBoost algorithm verified that important contributor. Further immunohistochemistry determined elevated tissues compared nontumor tissues. functional showed may promote through multiple cancer-related pathways suppress immune infiltration. Conclusion: In conclusion, anoikis-based can be biomarker play role development
Язык: Английский
Процитировано
14
International Immunopharmacology, Год журнала: 2023, Номер 115, С. 109684 - 109684
Опубликована: Янв. 9, 2023
Язык: Английский
Процитировано
14
Phytomedicine, Год журнала: 2024, Номер 129, С. 155714 - 155714
Опубликована: Май 5, 2024
Язык: Английский
Процитировано
5
International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 141524 - 141524
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Frontiers in Medicine, Год журнала: 2025, Номер 12
Опубликована: Март 6, 2025
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with an idiopathic origin, characterized by persistent mucosal inflammation. Anoikis programmed cell death mechanism activated during carcinogenesis to eliminate undetected isolated cells from the extracellular matrix. Although existing evidence indicates that anoikis contributes modulation of immune response, involvement anoikis-related genes (ARGs) in UC pathogenesis and their interaction infiltrating has not been thoroughly explored. The GSE75214, GSE92415, GSE16879 datasets were acquired integrated GEO database. Additionally, 58 ARGs identified through GSEA Key anoikis-DEGs using three machine learning algorithms, including least absolute shrinkage selection operator (LASSO) Cox regression, random forest (RF), support vector (SVM). Receiver operating characteristic (ROC) analysis was utilized evaluate diagnostic accuracy each gene. Subsequently, Single sample (ssGSEA) executed explore relationships within infiltration, subtypes, key anoikis-DEGs. Besides, unsupervised cluster conducted categorize samples into distinct subgroups, followed comparing subtype differences. Finally, upstream regulatory network constructed visualized. A comprehensive performed, revealing expression profile, correlation cells, enrichment analyses. We five (PDK4, CEACAM6, CFB, CX3CL1, HLA-DMA) demonstrated high for UC. Moreover, HLA-DMA exhibited positive associations UC, whereas PDK4 displayed negative all cells. Unsupervised enabled classification patients two clusters, both which gene profiles signaling pathways. Further, based upon network, TP53, RARB, RXRB, CTCF potentially exerted functions. Our as biomarkers These strongly associated infiltration innate adaptive well This study highlights role pathophysiology offers valuable insights further elucidating individualized therapy.
Язык: Английский
Процитировано
0
Journal of Cancer Research and Clinical Oncology, Год журнала: 2023, Номер 149(16), С. 15069 - 15083
Опубликована: Авг. 24, 2023
Язык: Английский
Процитировано
11