Identification and validation of an anoikis-associated gene signature to predict clinical character, stemness, IDH mutation, and immune filtration in glioblastoma

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Авг. 25, 2022

Background Glioblastoma (GBM) is the most prominent and aggressive primary brain tumor in adults. Anoikis a specific form of programmed cell death that plays key role invasion metastasis. The presence anti-anoikis factors associated with aggressiveness drug resistance. Methods non-negative matrix factorization algorithm was used for effective dimension reduction integrated datasets. Differences microenvironment (TME), stemness indices, clinical characteristics between two clusters were analyzed. Difference analysis, weighted gene coexpression network analysis (WGCNA), univariate Cox regression, least absolute shrinkage selection operator regression leveraged to screen prognosis-related genes construct risk score model. Immunohistochemistry performed evaluate expression representative specimens. relationship TME, stemness, traits, immunotherapy response assessed GBM pancancer. Results Two definite identified on basis anoikis-related expression. Patients assigned C1 characterized by shortened overall survival, higher suppressive immune infiltration levels, lower indices. We further constructed scoring model quantify regulatory patterns genes. group poor prognosis, cells differentiated phenotype, whereas exhibited opposite effects. In addition, patients frequency isocitrate dehydrogenase (IDH) mutations more sensitive immunotherapy. Drug sensitivity performed, revealing may benefit from drugs targeting PI3K/mTOR signaling pathway. Conclusion revealed potential relationships features, IDH mutation, elucidated their therapeutic value.

Язык: Английский

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Anoikis-Associated Lung Cancer Metastasis: Mechanisms and Therapies

Cancers, Год журнала: 2022, Номер 14(19), С. 4791 - 4791

Опубликована: Сен. 30, 2022

Tumor metastasis occurs in lung cancer, resulting tumor progression and therapy failure. Anoikis is a mechanism of apoptosis that combats metastasis; it inhibits the escape cells from native extracellular matrix to other organs. Deciphering regulators mechanisms anoikis cancer urgently needed treat cancer. Several natural synthetic products exhibit pro-anoikis potential vivo models. These include artonin E, imperatorin, oroxylin A, lupalbigenin, sulforaphane, renieramycin M, avicequinone B, carbenoxolone. This review summarizes current understanding molecular regulation relevant involved discusses therapeutic targeting treatment metastasis.

Язык: Английский

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Anoikis resistance––protagonists of breast cancer cells survive and metastasize after ECM detachment

Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)

Опубликована: Авг. 3, 2023

Abstract Breast cancer exhibits the highest global incidence among all tumor types. Regardless of type breast cancer, metastasis is a crucial cause poor prognosis. Anoikis, form apoptosis initiated by cell detachment from native environment, an outside-in process commencing with disruption cytosolic connectors such as integrin-ECM and cadherin-cell. This subsequently leads to intracellular cytoskeletal signaling pathway alterations, ultimately activating caspases initiating programmed death. Development anoikis-resistant phenotype critical initial step in metastasis. employs series stromal alterations suppress anoikis cells. Comprehensive investigation resistance mechanisms can inform strategies for preventing regressing metastatic cancer. The present review first outlines physiological anoikis, elucidating pathways, cytoskeleton, protein targets that transpire outside upon adhesion loss normal specific induced pathological changes various spatial structures during development are also discussed. Additionally, genetic loci altered summarized. Finally, micro-RNAs targeted drugs reported literature concerning compiled, keratocin being most functionally comprehensive.

Язык: Английский

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Identification of Anoikis-Related Subgroups and Prognosis Model in Liver Hepatocellular Carcinoma

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2862 - 2862

Опубликована: Фев. 2, 2023

Resistance to anoikis is a key characteristic of many cancer cells, promoting cell survival. However, the mechanism in hepatocellular carcinoma (HCC) remains unknown. In this study, we applied differentially expressed overlapping anoikis-related genes classify The Cancer Genome Atlas (TCGA) samples using an unsupervised cluster algorithm. Then, employed weighted gene coexpression network analysis (WGCNA) identify highly correlated and constructed prognostic risk model based on univariate Cox proportional hazards regression. This was validated external datasets from International Consortium (ICGC) Gene Expression Omnibus (GEO). Finally, used CIBERSORT algorithm investigate correlation between score immune infiltration. Our results showed that TCGA cohorts could be divided into two subgroups, with subgroup A having lower survival probability. Five (BAK1, SPP1, BSG, PBK DAP3) were identified as genes. Moreover, effectively predicted overall survival, which ICGC GEO datasets. addition, there strong infiltrating cells score. conclusion, subgroups HCC, significant for understanding molecular mechanisms treatment HCC.

Язык: Английский

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Deciphering the prognostic significance of anoikis-related lncRNAs in invasive breast cancer: from comprehensive bioinformatics analysis to functional experimental validation.

PubMed, Год журнала: 2024, Номер 16(1), С. 402 - 430

Опубликована: Янв. 5, 2024

The global prevalence of breast cancer necessitates the development innovative prognostic markers and therapeutic strategies. This study investigated implications anoikis-related long non-coding RNAs (ARLs) in invasive (IBC), which is an area that has not been extensively explored. By integrating RNA sequence transcriptome clinical data from Cancer Genome Atlas (TCGA) database employing advanced regression analyses, we devised a novel model based on ARL scores. scores correlated with diverse clinicopathological parameters, cellular pathways, distinct mutation patterns, immune responses, thereby affecting both cell infiltration anticipated responses to chemotherapy immunotherapy. Additionally, overexpression specific lncRNA,

Язык: Английский

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The emerging role of lactate in tumor microenvironment and its clinical relevance

Cancer Letters, Год журнала: 2024, Номер 590, С. 216837 - 216837

Опубликована: Март 26, 2024

Язык: Английский

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Nrf2 Modulation in Breast Cancer

Biomedicines, Год журнала: 2022, Номер 10(10), С. 2668 - 2668

Опубликована: Окт. 21, 2022

Reactive oxygen species (ROS) are identified to control the expression and activity of various essential signaling intermediates involved in cellular proliferation, apoptosis, differentiation. Indeed, ROS represents a double-edged sword supporting cell survival death. Many common pathological processes, including cancer types neurodegenerative diseases, inflammation oxidative stress triggers, or even initiate them. Keap1-Nrf2 is master antioxidant pathway cytoprotective mechanisms through Nrf2 target gene expression. Activation Nfr2 benefits cells early stages reduces level ROS. In contrast, hyperactivation creates context that supports both healthy cancerous cells, defending them against stress, chemotherapeutic drugs, radiotherapy. Considering dual role suppressing expanding determining its inhibitory/stimulatory position targeting can represent an impressive treatment. This review focused on modulators their roles sensitizing breast chemo/radiotherapy agents.

Язык: Английский

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Targeting tumor-associated MUC1 overcomes anoikis-resistance in pancreatic cancer

Translational research, Год журнала: 2022, Номер 253, С. 41 - 56

Опубликована: Авг. 27, 2022

Язык: Английский

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Identification of a novel anoikis‐related gene signature to predict prognosis and tumor microenvironment in lung adenocarcinoma

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

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ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis

Journal of Experimental & Clinical Cancer Research, Год журнала: 2023, Номер 42(1)

Опубликована: Март 22, 2023

Metastases are the major cause of cancer-related morbidity and mortality. By time cancer cells detach from their primary site to eventually spread distant sites, they need acquire ability survive in non-adherent conditions proliferate within a new microenvironment spite stressing that may severely constrain metastatic process. In this study, we gained insight into molecular mechanisms allowing an anchorage-independent manner, regardless both tumor-intrinsic variables nutrient culture conditions.3D spheroids derived lung adenocarcinoma (LUAD) breast were cultured either nutrient-rich or -restricted conditions. A multi-omics approach, including transcriptomics, proteomics, metabolomics, was used explore changes underlying transition 2 3D cultures. Small interfering RNA-mediated loss function assays validate role identified differentially expressed genes proteins H460 HCC827 LUAD as well MCF7 T47D cell lines.We found cultures is associated with significant expression involved metabolic reprogramming. particular, observed tumor spheroid growth implies overexpression ALDOC ENO2 glycolytic enzymes concomitant enhanced consumption glucose fructose production lactate. Transfection siRNA against determined reduction lactate production, viability size produced by H460, HCC827, MCF7, lines.Our results show survival supported drive metabolism towards production. Notably, finding valid for all lines have analyzed different environmental broader Validation mechanism other origin will be necessary broaden types. Future vivo studies assess metastasis.

Язык: Английский

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