Integrative Methylome and Transcriptome Characterization Identifies SERINC2 as a Tumor-Driven Gene for Papillary Thyroid Carcinoma

Ying, Tianxing; Wang, Xumeng; Yao, Yunjin; Yuan, Jimeng; Chen, Shitu; Wen, Liping; Chen, Zhijian; Luo, Chi; Sheng, Jinghao; Wang, Weibin; Teng, Lisong

doi:10.3390/cancers15010243

Cited by 7 publications

(4 citation statements)

References 40 publications

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“…Therefore, accurately identifying malignancy of thyroid tumors, especially those with indeterminate cytology, is essential for avoiding overtreatment and controlling tumor metastasis, which could benefit from supportive biomarkers. In this study, we identified RUNX1 methylation with high credibility and good accuracy in differentiating early-stage PTC cases from BTN subjects, suggesting it as a potential biomarker to aid the diagnostic process [47,48].…”

Section: Discussionmentioning

confidence: 77%

“…Both benign and malignant thyroid tumors have abnormal cell proliferation, DNA mutations or epigenetic changes, and large tumors are often accompanied by abundant angiogenesis and energy consumption [45]. Nevertheless, benign tumors don't invade neighboring tissue or metastasize and can be safely monitored with no or minimal treatment, whereas malignant tumors are usually aggressive and have a chance of recurrence and metastasis after resection of the focus, seriously threatening the life and health of patients [46,47]. Therefore, accurately identifying malignancy of thyroid tumors, especially those with indeterminate cytology, is essential for avoiding overtreatment and controlling tumor metastasis, which could benefit from supportive biomarkers.…”

Section: Discussionmentioning

confidence: 99%

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Discovery and Validation ofRUNX1DNA Methylation in Differentiating Papillary Thyroid Cancer from Benign Nodules

Yin

Huang

et al. 2023

Preprint

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Although most thyroid nodules can be diagnosed preoperatively by thyroid ultrasonography and fine-needle aspiration biopsy, it remains a challenge to accurately identify malignancy of thyroid nodules when the biopsy is indeterminate. This study aims to explore a novel biomarker to distinguish benign and malignant thyroid nodules. Tissue samples from patients with Stage I&II papillary thyroid carcinoma (PTC) and benign thyroid nodules (BTN) were collected for genome profiling by methylation EPIC 850K array and RNA-Sequencing. Genes with significantly differential DNA methylation and inverse mRNA expression were filtered out. The altered methylation ofRUNX1gene was validated in two independent case-control studies with a total of 699 formalin fixed paraffin-embedded (FFPE) samples using mass spectrometry and calculated by binary logistic regression analysis. Hypomethylation ofRUNX1gene in PTC patients compared to BTN subjects was verified in Validation I (140 PTC vs. 189 BTN, ORs ≥ 1.50 per-10% methylation,P≤ 4.40E-05, for all measurable CpG sites) and Validation II (184 PTC vs. 186 BTN, ORs ≥ 1.72 per-10% methylation,P≤ 2.38E-11, for all measurable CpG sites). Besides,RUNX1methylation achieved good accuracy in differentiating early-stage PTC from BTN in Validation I (AUC: 0.74) and Validation II (AUC: 0.79). Gender- and age-stratified analysis revealedRUNX1hypomethylation as an important risk factor for thyroid disease in younger women. We disclosed a significant association betweenRUNX1hypomethylation and PTC, suggestingRUNX1methylation based on FFPE tissue samples as a potential biomarker for predicting malignancy of thyroid nodules.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Discovery and Validation ofRUNX1DNA Methylation in Differentiating Papillary Thyroid Cancer from Benign Nodules

Yin

Huang

et al. 2023

Preprint

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“…DNA methylation, the most widely studied epigenetic mechanism, varies in different cancers, and is notably altered in thyroid cancer [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Now, the role of DNA methylation in cancer is being widely studied to determine markers that might guide treatment.…”

Section: Introductionmentioning

confidence: 99%

“…The BRAF V600E mutation is common in thyroid cancer [ 13 , 15 , 16 , 18 , 22 , 23 , 25 ], as is DNA methylation [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. However, the interaction or association between them is not well-studied.…”

Section: Introductionmentioning

confidence: 99%

Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer

et al. 2023

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The BRAF V600E mutation and DNA promoter methylation play important roles in the pathogenesis of thyroid cancer (TC). However, the association of these genetic and epigenetic alterations is not clear. In this study, using paired tumor and surrounding normal tissue from the same patients, on a genome-wide scale we tried to identify (a) any association between BRAF mutation and DNA promoter methylation, and (b) if the molecular findings may provide a basis for therapeutic intervention. We included 40 patients with TC (female = 28, male = 12) without distant metastasis. BRAF mutation was present in 18 cases. We identified groups of differentially methylated loci (DML) that are found in (a) both BRAF mutant and wild type, (b) only in BRAF mutant tumors, and (c) only in BRAF wild type. BRAF mutation-specific promoter loci were more frequently hypomethylated, whereas BRAF wild-type-specific loci were more frequently hypermethylated. Common DML were enriched in cancer-related pathways, including the mismatch repair pathway and Wnt-signaling pathway. Wild-type-specific DML were enriched in RAS signaling. Methylation status of checkpoint signaling genes, as well as the T-cell inflamed genes, indicated an opportunity for the potential use of PDL1 inhibitors in BRAF mutant TC. Our study shows an association between BRAF mutation and methylation in TC that may have biological significance.

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Serinc2 Drives the Progression of Cervical Cancer Through Regulating Myc Pathway

Wang,

Jiang,

2024

Cancer Medicine

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BackgroundAs one of the most common malignancies, cervical cancer (CC) seriously affects women's health. This study aimed to investigate the biological function of Serinc2 in CC.MethodsSerinc2 expression was surveyed utilizing immunohistochemistry, western blot, and qRT‐PCR. CC cell viability, invasion, proliferation, migration, and apoptosis, were detected via CCK‐8, Transwell assay, colony formation, wound healing assay, and flow cytometry. Glucose consumption, lactate production, and ATP levels were determined by the corresponding kit. The protein expression of c‐Myc, PDK1, HK2, PFKP, LDHA, Snail, Vimentin, N‐cadherin, and E‐cadherin was detected via western blot. The interaction between the promoter of PFKP and Myc was confirmed through luciferase reporter assay and Chip assay. In vivo, to evaluate the function of Serinc2 on tumor growth, a xenograft mouse model was used.ResultsIn CC tissues and cells, Serinc2 was upregulated. In CC cells, knockdown of Serinc2 suppressed cell invasion, proliferation, migration, decreased the expression of Snail, Vimentin, N‐cadherin, HK2, PFKP, LDHA, and PDK1, increased E‐cadherin expression, reduced glucose consumption and the production of lactate and ATP, and induced cell apoptosis; Serinc2 overexpression led to the opposite results. Mechanically, Serinc2 promoted Myc expression, and Myc induced PFKP expression. Furthermore, overexpressed Myc abolished the inhibitive influences of Serinc2 knockdown on the malignant behaviors of CC cells. Additionally, knockdown of Serinc2 inhibited tumor growth and reduced the protein expression of c‐Myc, PFKP, LDHA, and PDK1 in vivo.ConclusionsKnockdown of Serinc2 inhibited the malignant progression of CC, which was achieved via Myc pathway. Our study provides novel insight into CC pathogenesis.

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Integrative Methylome and Transcriptome Characterization Identifies SERINC2 as a Tumor-Driven Gene for Papillary Thyroid Carcinoma

Cited by 7 publications

References 40 publications

Discovery and Validation ofRUNX1DNA Methylation in Differentiating Papillary Thyroid Cancer from Benign Nodules

Discovery and Validation ofRUNX1DNA Methylation in Differentiating Papillary Thyroid Cancer from Benign Nodules

Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer

Serinc2 Drives the Progression of Cervical Cancer Through Regulating Myc Pathway

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