Characterization of aging cancer-associated fibroblasts draws implications in prognosis and immunotherapy response in low-grade gliomas

Zhou, Zijian; Wei, Jinhong; Kuang, Lijun; Zhang, Ke; Liu, Yini; He, Zhongming; Li, Luo; Lü, Bin

doi:10.3389/fgene.2022.897083

Cited by 6 publications

(4 citation statements)

References 71 publications

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“…These alterations can change CAF phenotype, facilitate metastasis, and decrease response to therapy in cancer cells ( Turrell et al, 2023 ). Despite growing awareness of the dynamic evolution of CAFs ( Zhou et al, 2022 ), the secretory profile and modulatory role of CAFs in different stages of their life cycle are not fully characterized yet. Dissecting these changes in CAF phenotype is needed to guide CAF-targeting approaches effectively.…”

Section: Discussion and Perspectivesmentioning

confidence: 99%

Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer

Ozmen,

Demir,

Ozcan

2024

Front. Mol. Biosci.

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Enhanced knowledge of the interaction of cancer cells with their environment elucidated the critical role of tumor microenvironment in tumor progression and chemoresistance. Cancer-associated fibroblasts act as the protagonists of the tumor microenvironment, fostering the metastasis, stemness, and chemoresistance of cancer cells and attenuating the anti-cancer immune responses. Gastric cancer is one of the most aggressive cancers in the clinic, refractory to anti-cancer therapies. Growing evidence indicates that cancer-associated fibroblasts are the most prominent risk factors for a poor tumor immune microenvironment and dismal prognosis in gastric cancer. Therefore, targeting cancer-associated fibroblasts may be central to surpassing resistance to conventional chemotherapeutics, molecular-targeted agents, and immunotherapies, improving survival in gastric cancer. However, the heterogeneity in cancer-associated fibroblasts may complicate the development of cancer-associated fibroblast targeting approaches. Although single-cell sequencing studies started dissecting the heterogeneity of cancer-associated fibroblasts, the research community should still answer these questions: “What makes a cancer-associated fibroblast protumorigenic?”; “How do the intracellular signaling and the secretome of different cancer-associated fibroblast subpopulations differ from each other?”; and “Which cancer-associated fibroblast subtypes predominate specific cancer types?”. Unveiling these questions can pave the way for discovering efficient cancer-associated fibroblast targeting strategies. Here, we review current knowledge and perspectives on these questions, focusing on how CAFs induce aggressiveness and therapy resistance in gastric cancer. We also review potential therapeutic approaches to prevent the development and activation of cancer-associated fibroblasts via inhibition of CAF inducers and CAF markers in cancer.

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Section: Discussion and Perspectivesmentioning

confidence: 99%

Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer

Ozmen,

Demir,

Ozcan

2024

Front. Mol. Biosci.

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“…Two large statistical transcriptome and genomic analyses based on large databases of human gliomas revealed additional CAP markers whose expression correlates with patient prognosis. In particular, two clusters were observed in low-grade gliomas, with the first cluster representing cases with a poorer prognosis, a greater number of CAFs and marked expression of chitinase-3-like protein 1 (CHI3L1), a glycoprotein known to be associated with activation of antiapoptotic signaling pathways [114]. Statistical analysis of another database containing both low-grade and high-grade gliomas confirmed higher expression of a large number of CAF-associated cytokines in the high-grade group [115].…”

Section: Other Cellular Components Of the Tumor Environment In Gliomasmentioning

confidence: 99%

Cellular Components of the Tumor Environment in Gliomas—What Do We Know Today?

Nafe,

Hattingen

2023

Biomedicines

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A generation ago, the molecular properties of tumor cells were the focus of scientific interest in oncology research. Since then, it has become increasingly apparent that the tumor environment (TEM), whose major components are non-neoplastic cell types, is also of utmost importance for our understanding of tumor growth, maintenance and resistance. In this review, we present the current knowledge concerning all cellular components within the TEM in gliomas, focusing on their molecular properties, expression patterns and influence on the biological behavior of gliomas. Insight into the TEM of gliomas has expanded considerably in recent years, including many aspects that previously received only marginal attention, such as the phenomenon of phagocytosis of glioma cells by macrophages and the role of the thyroid-stimulating hormone on glioma growth. We also discuss other topics such as the migration of lymphocytes into the tumor, phenotypic similarities between chemoresistant glioma cells and stem cells, and new clinical approaches with immunotherapies involving the cells of TEM.

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“…The rapid progress in highthroughput microarray technologies has enabled the identification of putative novel biomarkers, genetic variations, and biological pathways, thereby enhancing our comprehension of the pathogenesis and therapeutic intervention of various ailments (Li et al, 2021;. WGCNA (Langfelder and Horvath, 2008;Abu-Jamous and Clust, 2018;Zhou Z et al, 2022) and machine learning techniques are gradually improving, and these bioinformatics tools can be employed for providing great prospects for identifying the potential molecular mechanisms, biomarkers, and therapeutic targets for smoking-related OP and COPD, as well as other complex diseases. These technologies enable researchers to explore large datasets and identify key molecular pathways and biomarkers, leading to the discovery of new therapeutic interventions and improved patient outcomes (Kumar et al, 2021;.…”

Section: Introductionmentioning

confidence: 99%

Exploring the shared gene signatures of smoking-related osteoporosis and chronic obstructive pulmonary disease using machine learning algorithms

Wang

Chen

et al. 2023

Front. Mol. Biosci.

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Objectives: Cigarette smoking has been recognized as a predisposing factor for both osteoporosis (OP) and chronic obstructive pulmonary disease (COPD). This study aimed to investigate the shared gene signatures affected by cigarette smoking in OP and COPD through gene expression profiling.Materials and methods: Microarray datasets (GSE11784, GSE13850, GSE10006, and GSE103174) were obtained from Gene Expression Omnibus (GEO) and analyzed for differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA). Least absolute shrinkage and selection operator (LASSO) regression method and a random forest (RF) machine learning algorithm were used to identify candidate biomarkers. The diagnostic value of the method was assessed using logistic regression and receiver operating characteristic (ROC) curve analysis. Finally, immune cell infiltration was analyzed to identify dysregulated immune cells in cigarette smoking-induced COPD.Results: In the smoking-related OP and COPD datasets, 2858 and 280 DEGs were identified, respectively. WGCNA revealed 982 genes strongly correlated with smoking-related OP, of which 32 overlapped with the hub genes of COPD. Gene Ontology (GO) enrichment analysis showed that the overlapping genes were enriched in the immune system category. Using LASSO regression and RF machine learning, six candidate genes were identified, and a logistic regression model was constructed, which had high diagnostic values for both the training set and external validation datasets. The area under the curves (AUCs) were 0.83 and 0.99, respectively. Immune cell infiltration analysis revealed dysregulation in several immune cells, and six immune-associated genes were identified for smoking-related OP and COPD, namely, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), tissue-type plasminogen activator (PLAT), sodium channel 1 subunit alpha (SCNN1A), sine oculis homeobox 3 (SIX3), sperm-associated antigen 9 (SPAG9), and vacuolar protein sorting 35 (VPS35).Conclusion: The findings suggest that immune cell infiltration profiles play a significant role in the shared pathogenesis of smoking-related OP and COPD. The results could provide valuable insights for developing novel therapeutic strategies for managing these disorders, as well as shedding light on their pathogenesis.

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Characterization of aging cancer-associated fibroblasts draws implications in prognosis and immunotherapy response in low-grade gliomas

Cited by 6 publications

References 71 publications

Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer

Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer

Cellular Components of the Tumor Environment in Gliomas—What Do We Know Today?

Exploring the shared gene signatures of smoking-related osteoporosis and chronic obstructive pulmonary disease using machine learning algorithms

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