Somatic Mutation Profiling of Papillary Thyroid Carcinomas by Whole-exome Sequencing and Its Relationship with Clinical Characteristics

Qi, Tingyue; Rong, Xin; Feng, Qingling; Sun, Hongyan; Cao, Haiyan; Yang, Yan; Feng, Hao; Zhu, Linhai; Wang, Lei; Du, Qiu

doi:10.7150/ijms.50916

Cited by 6 publications

(4 citation statements)

References 74 publications

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“…Extracellular signal-regulated kinase (ERK) and nuclear factor kappa B (NF-κB) also play essential roles in many biological processes, such as cell growth, tumorigenesis and autophagy and apoptosis [ 39 – 42 ]. More importantly, in a previous study, the BRAF V600E mutant notably activated the MAPK signaling pathway in BRAF-mutant thyroid cancers [ 43 , 44 ]. In this study, RNA sequence revealed that WT1 is closely associated with PI3K/AKT signaling network, mTOR signaling cascades, MAPK signaling pathway and NF-kappa B signaling pathway.…”

Section: Discussionmentioning

confidence: 97%

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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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Section: Discussionmentioning

confidence: 97%

“…Then, the cells were placed in 4% paraformaldehyde for approximately 30 min, and then, 0.03% Triton X-100 was added and incubated for 20 min. The manufacturer’s protocol for the immunofluorescence assay was followed as previously described [ 44 ]. The images were analyzed by a fluorescence microscope and ImageJ software (Version 1.8.0).…”

Section: Methodsmentioning

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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“…The activation of the ABL tyrosine kinases was also detected in breast, colon, lung, kidney and melanomas ( Greuber et al, 2013 ). Although this mutation has been reported to have a high prevalence in PTC patients, its role in PTC is yet to be determined ( Qi et al, 2021 ). Whether there is an effect of BCR -rs372013175 in gene fusion process between BCR and ABL , remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Changes in antioxidant status and DNA repair capacity are corroborated with molecular alterations in malignant thyroid tissue of patients with papillary thyroid cancer

Eng,

Abdul Aziz,

et al. 2023

Front. Mol. Biosci.

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Introduction: Papillary thyroid cancer (PTC) accounts for approximately 80% of all thyroid cancer cases. The mechanism of PTC tumourigenesis is not fully understood, but oxidative imbalance is thought to play a role. To gain further insight, this study evaluated antioxidant status, DNA repair capacity and genetic alterations in individuals diagnosed with benign thyroid lesion in one lobe (BTG) and PTC lesion in another.Methods: Individuals with coexisting BTG and PTC lesions in their thyroid lobes were included in this study. Reactive oxygen species (ROS) level, ABTS radical scavenging activity, ferric reducing antioxidant capacity, glutathione peroxidase and superoxide dismutase activities were measured in the thyroid tissue lysate. The expression of selected genes and proteins associated with oxidative stress defence and DNA repair were analysed through quantitative real-time PCR and Western blotting. Molecular alterations in genomic DNA were analysed through whole-exome sequencing and the potentially pathogenic driver genes filtered through Cancer-Related Analysis of Variants Toolkit (CRAVAT) analysis were subjected to pathway enrichment analysis using Metascape.Results: Significantly higher ROS level was detected in the PTC compared to the BTG lesions. The PTC lesions had significantly higher expression of GPX1, SOD2 and OGG1 but significantly lower expression of CAT and PRDX1 genes than the BTG lesions. Pathway enrichment analysis identified “regulation of MAPK cascade,” “positive regulation of ERK1 and ERK2 cascade” and “negative regulation of reactive oxygen species metabolic process” to be significantly enriched in the PTC lesions only. Four pathogenic genetic variants were identified in the PTC lesions; BRAFV600E, MAP2K7-rs2145142862, BCR-rs372013175 and CD24 NM_001291737.1:p.Gln23fs while MAP3K9 and G6PD were among 11 genes that were mutated in both BTG and PTC lesions.Conclusion: Our findings provided further insight into the connection between oxidative stress, DNA damage, and genetic changes associated with BTG-to-PTC transformation. The increased oxidative DNA damage due to the heightened ROS levels could have heralded the BTG-to-PTC transformation, potentially through mutations in the genes involved in the MAPK signalling pathway and stress-activated MAPK/JNK cascade. Further in-vitro functional analyses and studies involving a larger sample size would need to be carried out to validate the findings from this pilot study.

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“…PTCs are inert and one of the cancers with the lowest mutation density. BRAF V600 is the most common and specific genetic alteration in PTC [ 113 , 114 ]. FTC accounts for about 5% of thyroid cancer.…”

Section: Application Of Single-cell Sequencing In the Diagnosis And T...mentioning

confidence: 99%

Research progress and application of single-cell sequencing in head and neck malignant tumors

Qu,

Gong,

Deng

et al. 2023

Cancer Gene Ther

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Single-cell sequencing (SCS) is a technology that separates thousands of cells from the organism and accurately analyzes the genetic material expressed in each cell using high-throughput sequencing technology. Unlike the traditional bulk sequencing approach, which can only provide the average value of a cell population and cannot obtain specific single-cell data, single-cell sequencing can identify the gene sequence and expression changes of a single cell, and reflects the differences between genetic material and protein between cells, and ultimately the role played by the tumor microenvironment. single-cell sequencing can further explore the pathogenesis of head and neck malignancies from the single-cell biological level and provides a theoretical basis for the clinical diagnosis and treatment of head and neck malignancies. This article will systematically introduce the latest progress and application of single-cell sequencing in malignant head and neck tumors.

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Somatic Mutation Profiling of Papillary Thyroid Carcinomas by Whole-exome Sequencing and Its Relationship with Clinical Characteristics

Cited by 6 publications

References 74 publications

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

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

Changes in antioxidant status and DNA repair capacity are corroborated with molecular alterations in malignant thyroid tissue of patients with papillary thyroid cancer

Research progress and application of single-cell sequencing in head and neck malignant tumors

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