Prognostic and Therapeutic Role of Angiogenic Microenvironment in Thyroid Cancer

Melaccio, Assunta; Sgaramella, Lucia Ilaria; Pasculli, Alessandro; Meo, Giovanna Di; Gurrado, Angela; Prete, Francesco Paolo; Vacca, Angelo; Ria, Roberto; Testini, Mario

doi:10.3390/cancers13112775

Cited by 12 publications

(8 citation statements)

References 167 publications

(213 reference statements)

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“…Several experimental and clinical data suggest that other molecules may have a role in the prognostic stratification of TC patients. These include immune checkpoint factors and immune-related signature (IRS), estrogen receptors, Vitamin D, tumor angiogenic microenvironment, circular RNAs, long noncoding RNAs, and the angiotensin converting enzymes ACE and ACE2 [ 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 ]. However, all of them are awaiting validation in large case studies.…”

Section: Thyroid Cancer Patient’s Stagingmentioning

confidence: 99%

Papillary Thyroid Cancer Prognosis: An Evolving Field

Ulisse

Baldini

Lauro

et al. 2021

Cancers

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Over the last few years, a great advance has been made in the comprehension of the molecular pathogenesis underlying thyroid cancer progression, particularly for the papillary thyroid cancer (PTC), which represents the most common thyroid malignancy. Putative cancer driver mutations have been identified in more than 98% of PTC, and a new PTC classification into molecular subtypes has been proposed in order to resolve clinical uncertainties still present in the clinical management of patients. Additionally, the prognostic stratification systems have been profoundly modified over the last decade, with a view to refine patients’ staging and being able to choose a clinical approach tailored on single patient’s needs. Here, we will briefly discuss the recent changes in the clinical management of thyroid nodules, and review the current staging systems of thyroid cancer patients by analyzing promising clinicopathological features (i.e., gender, thyroid auto-immunity, multifocality, PTC histological variants, and vascular invasion) as well as new molecular markers (i.e., BRAF/TERT promoter mutations, miRNAs, and components of the plasminogen activating system) potentially capable of ameliorating the prognosis of PTC patients.

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Section: Thyroid Cancer Patient’s Stagingmentioning

confidence: 99%

Papillary Thyroid Cancer Prognosis: An Evolving Field

Ulisse

Baldini

Lauro

et al. 2021

Cancers

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“…Therefore, the lncRNA that recognizes EMT may be a marker for early detection of cancer recurrence ( 26 ). LncRNAs are receiving increasing attention as a class of tumor biomarkers for early screening, targeted therapy, and prognostic evaluation ( 27 ). There is mounting evidence that lncRNAs are closely associated with the recurrence of tumors ( 28 , 29 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of m6A-related lncRNAs for thyroid cancer recurrence

Wang¹,

Su²,

Wei³

et al. 2023

Gland Surg

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Background: Although the prognosis of thyroid cancer (THCA) is generally good, many patients have a high risk of recurrence after treatment. N6-methyladenosine (m6A)-related long noncoding RNAs (lncRNAs) have been extensively studied in recent years. However, the potential of m6A-related lncRNAs to predict recurrence in THCA is unknown.Methods: RNA sequencing (RNA-seq) data and clinical information for THCA were downloaded fromThe Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs (DELs) were identified using the R package DESeq2. A coexpression network based on m6A-related genes and lncRNAs was constructed. The CIBERSORT algorithm and gene set enrichment analysis (GSEA) were used for immune-infiltrating cell estimation and clustering functional enrichment analysis, respectively. A Kaplan-Meier plot was used for prognostic analysis based on m6A-associated lncRNA risk patterns. The expression of lncRNAs in recurrent and nonrecurrent THCA tissues was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR).Results: A network of m6A-related lncRNAs containing 8 lncRNAs was constructed with good predictive power for recurrence in THCA. A total of 3 clusters were obtained, and cluster 1 was most associated with THCA recurrence. We found significantly lower levels of CD8 T cells and follicular helper T cells, and significantly higher levels of dendritic cells (DCs), M2 macrophages, resting DCs, regulatory T cells, and mast cells in cluster 1 patients. Pathway analysis revealed significant enrichment in natural killer cellmediated cytotoxicity, butyrate metabolism, and cell adhesion molecules in cluster 1. The m6A-related lncRNA risk model was effective in predicting progression-free survival (PFS) in patients with THCA recurrence. RT-qPCR analysis based on 40 THCA clinical samples from our center found the risk model to be a good predictor of recurrence in THCA patients.Conclusions: In summary, m6A-related lncRNAs may provide a novel predictive method for prognostic relapse in THCA patients.

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“…The role of microenvironment in thyroid carcinogenesis has been clarified [ 15 ]. The components of microenvironment (extracellular matrix components (ECM) and stromal cells) surround and support cancer cells, interacting with them through cell-cell and cell-extracellular matrix interactions [ 16 ]. These are consistent with the results we obtained; through GO analysis, we concluded that the role of quercetin in PTC is enriched in processes such as response to extracellular stimulus, oxidoreductase activity, and extracellular matrix organization.…”

Section: Discussionmentioning

confidence: 99%

To Explore the Inhibitory Mechanism of Quercetin in Thyroid Papillary Carcinoma through Network Pharmacology and Experiments

et al. 2022

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Quercetin, a flavonoid with anti-inflammatory and anticancer properties, is expected to be an innovative anticancer therapeutic agent for papillary thyroid carcinoma (PTC). However, the downstream signaling pathways that mediate quercetin-dependent anticancer properties remain to be deciphered. Herein, potential targets of quercetin were screened with several bioinformatic avenues including PharmMapper, Gene Expression Omnibus (GEO) database, protein–protein interaction (PPI) network, and molecular docking. Besides, western blot, CCK-8 transwell analysis of migration and invasion, flow cytometric analysis, and colony formation assays were performed to investigate the underlying mechanism. We found four core nodes (MMP9, JUN, SPP1, and HMOX1) by constructing a PPI network with 23 common targets. Through functional enrichment analysis, we confirmed that the above four target genes are enriched in the TNF, PI3K-AKT, and NF-κB signaling pathways, which are involved in the inflammatory microenvironment and inhibit the development and progression of tumors. Furthermore, molecular docking results demonstrated that quercetin shows strong binding efficiency with the proteins encoded by these 4 key proteins. Finally, quercetin displayed strong antitumor efficacy in PTC cell lines. In this research, we demonstrated the application of network pharmacology in evaluating the mechanisms of action and molecular targets of quercetin, which regulates a variety of proteins and signaling pathways in PTC. These data might explain the mechanism underlying the anticancer effects of quercetin in PTC.

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Prognostic and Therapeutic Role of Angiogenic Microenvironment in Thyroid Cancer

Cited by 12 publications

References 167 publications

Papillary Thyroid Cancer Prognosis: An Evolving Field

Papillary Thyroid Cancer Prognosis: An Evolving Field

Identification of m6A-related lncRNAs for thyroid cancer recurrence

To Explore the Inhibitory Mechanism of Quercetin in Thyroid Papillary Carcinoma through Network Pharmacology and Experiments

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