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Multi-omics analysis revealed TEK and AXIN2 are potential biomarkers in multifocal papillary thyroid cancer
Ga Hyun Kim1, Hye Jin Heo2, Ji Wan Kang1
1Interdisciplinary Program of Genomic Data Science, Pusan National University, Yangsan, Republic of Korea.
Background:
Papillary thyroid carcinoma (PTC), the most common endocrine cancer, accounts for 80-85% of all malignant thyroid tumors. This study focused on identifying targets that affect the multifocality of PTC. In a previous study, we determined 158 mRNAs related to multifocality in BRAF-mutated PTC using The Cancer Genome Atlas.
Methods:
We used multi-omics data (miRNAs and mRNAs) to identify the regulatory mechanisms of the investigated mRNAs. miRNA inhibitors were used to determine the relationship between mRNAs and miRNAs. We analyzed the target protein levels in patient sera using ELISA and immunohistochemical staining of patients' tissues.
Results:
We identified 44 miRNAs that showed a negative correlation with mRNA expression. Using in vitro experiments, we identified four miRNAs that inhibit TEK and/or AXIN2 among the target mRNAs. We also showed that the downregulation of TEK and AXIN2 decreased the proliferation and migration of BRAF ( +) PTC cells. To evaluate the diagnostic ability of multifocal PTC, we examined serum TEK or AXIN2 in unifocal and multifocal PTC patients using ELISA, and showed that the serum TEK in multifocal PTC patients was higher than that in the unifocal PTC patients. The immunohistochemical study showed higher TEK and AXIN2 expression in multifocal PTC than unifocal PTC.
Conclusions:
Both TEK and AXIN2 play a potential role in the multifocality of PTC, and serum TEK may be a diagnostic marker for multifocal PTC.
Insights
Researchers identified TEK and AXIN2 as key factors in multifocal papillary thyroid carcinoma (PTC). Elevated serum TEK shows potential as a diagnostic marker for multifocal PTC, aiding in early detection.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Papillary thyroid carcinoma (PTC) is the most common endocrine cancer, representing 80-85% of thyroid malignancies.
- Multifocality is a key characteristic of PTC, influencing treatment and prognosis.
- Previous research identified 158 mRNAs linked to multifocality in BRAF-mutated PTC.
Purpose of the Study:
- To identify molecular targets regulating PTC multifocality.
- To elucidate the regulatory mechanisms involving miRNAs and mRNAs in PTC.
- To evaluate TEK and AXIN2 as potential diagnostic markers for multifocal PTC.
Main Methods:
- Utilized multi-omics data (miRNAs and mRNAs) to uncover regulatory networks.
- Employed miRNA inhibitors to confirm mRNA-miRNA interactions.
- Analyzed TEK and AXIN2 protein levels in patient sera (ELISA) and tissues (immunohistochemistry).
Main Results:
- Identified 44 miRNAs negatively correlated with mRNA expression.
- Discovered four miRNAs inhibiting TEK and/or AXIN2.
- Demonstrated that TEK and AXIN2 downregulation reduced PTC cell proliferation and migration.
- Found significantly higher serum TEK levels and tissue expression of TEK and AXIN2 in multifocal PTC patients compared to unifocal cases.
Conclusions:
- TEK and AXIN2 are implicated in the multifocality of PTC.
- Serum TEK presents potential as a novel diagnostic biomarker for multifocal PTC.
