방사선의학 웹진

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Abstract
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.

Affiliations

Ga Hyun Kim #  1 , Hye Jin Heo #  2 , Ji Wan Kang #  1 , Eun-Kyung Kim  2 , Seung Eun Baek  2 , Keunyoung Kim  3 , In Joo Kim  3 , Sunghwan Suh  4 , Byung-Joo Lee  5 , Yun Hak Kim #  6   7   8 , Kyoungjune Pak #  9
1 Interdisciplinary Program of Genomic Data Science, Pusan National University, Yangsan, Republic of Korea.
2 Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
3 Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
4 Department of Internal Medicine, Dong-A University College of Medicine, Busan, Republic of Korea.
5 Department of Otorhinolaryngology-Head and Neck Surgery, Pusan National University Hospital, Busan, Republic of Korea.
6 Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea. yunhak10510@pusan.ac.kr.
7 Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea. yunhak10510@pusan.ac.kr.
8 Department of Biomedical Informatics, School of Medicine, Pusan National University, Yangsan, Republic of Korea. yunhak10510@pusan.ac.kr.
9 Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea. ilikechopin@me.com.
# Contributed equally.