ADORA1 is a diagnostic-related biomarker and correlated with immune infiltrates in papillary thyroid carcinoma

Lin, Xu; Wang, Zhiyong; Xue, Gang; Qin, Xiaojing; Wu, Jing; Zhang, Geng

doi:10.7150/jca.50743

Cited by 10 publications

(7 citation statements)

References 37 publications

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“…Besides, ADORA1 was overexpressed and played an oncogenic role in PTC. Therefore, it can be a diagnostic and a prognostic biomarker [ 44 ]. In this study, we focused on the gene signatures in complex TME, which affected the progression and prognosis of THCA.…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of plasma complement factor B (CFB) in thyroid carcinoma

Shi

Sun

et al. 2021

Bioengineered

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Stromal and immune cells are major components of tumor microenvironment (TME) and affect the growth and development of thyroid carcinoma (THCA). However, data on the exact mechanisms that define the relationship between the TME and THCA remain scant. We calculated stromal and immune cells scores and the proportion of tumor-infiltrating immune cells (TICs) by CIBERSORT and ESTIMATE based on the THCA gene expression data from the Cancer Genome Atlas (TCGA). In addition, we evaluated differentially expressed genes (DEGs) from high- and low-score groups and performed functional enrichment analysis. Furthermore, our data show a significant correlation between plasma complement factor B (CFB) and PTC development and prognosis. Gene Set Enrichment Analysis (GSEA) demonstrated that the CFB was mainly enriched in immune response pathways. The expression of CFB was positively correlated with T cells CD8, Macrophages M1, Plasma cells, T cells CD4 memory activated, T cells follicular helper and T cells regulatory (Tregs), whereas negatively correlated with Eosinophils, Macrophages M0, Macrophages M2, Mast cells resting, T cells CD4 memory resting in the TME. Finally, the expression level of CFB was verified by other cohorts from Gene Expression Omnibus (GEO) database and quantitative Real-Time PCR (qRT-PCR) analyses, which was consistent with the results of bioinformatic analysis. Taken together, our data demonstrated that the CFB could be a prognostic marker for THCA and its expression influences the infiltration of immune cells.

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Section: Discussionmentioning

confidence: 99%

The prognostic value of plasma complement factor B (CFB) in thyroid carcinoma

Shi

Sun

et al. 2021

Bioengineered

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“…According to previous study, the PTC incidence was 1.80 per 100,000 males and 6.20 per 100,000 in females worldwide [ 28 ]. Despite the improvement in current treatments, patients with PTC tend to develop distant metastases or recurrence and have poor prognosis because of complex biological characteristics and unclear pathological mechanisms [ 29 ]. In this study, we found that WT1 is highly expressed in PTC patients, and higher WT1 expression is predictive of worse overall survival time.…”

Section: Discussionmentioning

confidence: 99%

BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma

Chen

Lin

Lin³

et al. 2022

J Transl Med

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Background Papillary thyroid carcinoma (PTC) is one of most prevalent malignant endocrine neoplasms, and it is associated with a high frequency of BRAF gene mutations, which lead to lymphatic metastasis and distant metastasis that promote tumor progression. The molecular mechanism of PTC and the role of BRAF mutation in PTC progression and development need to be further elucidated. Methods In this study, a comprehensive bioinformatics analysis was performed to identify the differentially expressed genes and signaling pathways in thyroid cancer patients carrying mutant BRAF. Then, we confirmed the prognostic role of WT1 in thyroid cancer patients. Immunohistochemistry was performed to measure the expression profile of WT1 in PTC tissue. Lentivirus shWT1 was transfected into BRAFV600E (mutant) PTC cells to stably inhibit WT1 expression. CCK-8, EdU, immunofluorescence, colony formation, cell migration, cell wound healing, apoptosis and autophagy assays were performed to assess the biological functions of WT1 in BRAFV600E PTC cells. RNA sequencing, immunohistochemistry and immunoblotting were performed to explore the molecular mechanism of WT1 in BRAFV600E PTC cells. Results The results confirmed that “epithelial cell proliferation”, “apoptosis” and “selective autophagy” were closely associated with this BRAF mutant in these thyroid cancer patients. Knocking down BRAF-activated WT1 effectively inhibited the proliferation and migration of BRAFV600E PTC cells. Silencing WT1 significantly inhibited autophagy and promoted the apoptosis of BRAFV600E PTC cells. Mechanistic investigations showed that silencing WT1 expression remarkably suppressed the AKT/mTOR and ERK/P65 signaling pathways in BRAFV600E PTC cells. Conclusion All these results indicate that WT1 is a promising prognostic biomarker and facilitates PTC progression and development of cells carrying the BRAFV600E mutation.

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“…198 Nevertheless, the crystal structure of JW55 bound to the catalytic domain of tankyrase 2 was resolved; the two carbonyl groups of the compound are hydrogen-bonded to the backbone amides of D1045 and Y1060 in addition to a π−π interaction of the furyl moiety with H1048 (Figure 9I). Since its discovery, JW55 has scarcely been used as an investigational tool in cancer research, 63,199 presumably due to much weaker potency than other early generation tankyrase inhibitors.…”

Section: Small-molecule Inhibitors Of Tankyrases: From Discovery To T...mentioning

confidence: 99%

Small-Molecule Inhibitors of Tankyrases as Prospective Therapeutics for Cancer

Yang

Sykes

et al. 2022

J. Med. Chem.

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Tankyrases are multifunctional poly(adenosine diphosphate-ribose) polymerases that regulate diverse biological processes including telomere maintenance and cellular signaling. These processes are often implicated in a number of human diseases, with cancer being the most prevalent example. Accordingly, tankyrase inhibitors have gained increasing attention as potential therapeutics. Since the discovery of XAV939 and IWR-1 as the first tankyrase inhibitors over two decades ago, tankyrase-targeted drug discovery has made significant progress. This review starts with an introduction of tankyrases, with emphasis placed on their cancer-related functions. Small-molecule inhibitors of tankyrases are subsequently delineated based on their distinct modes of binding to the enzymes. In addition to inhibitors that compete with oxidized nicotinamide adenine dinucleotide (NAD+) for binding to the catalytic domain of tankyrases, non-NAD+-competitive inhibitors are detailed. This is followed by a description of three clinically trialled tankyrase inhibitors. To conclude, some of challenges and prospects in developing tankyrase-targeted cancer therapies are discussed.

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ADORA1 is a diagnostic-related biomarker and correlated with immune infiltrates in papillary thyroid carcinoma

Cited by 10 publications

References 37 publications

The prognostic value of plasma complement factor B (CFB) in thyroid carcinoma

The prognostic value of plasma complement factor B (CFB) in thyroid carcinoma

BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma

Small-Molecule Inhibitors of Tankyrases as Prospective Therapeutics for Cancer

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