AUTHOR=Zhang Qiaoyue , Li Jing , Shen Hengyan , Bai Xinyu , Zhang Tao , Liu Ping 

TITLE=Screening and validation of lymph node metastasis risk-factor genes in papillary thyroid carcinoma

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.991906

DOI=10.3389/fendo.2022.991906

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>Although most papillary thyroid carcinoma (PTC) cases have a good prognosis, some PTCs are more aggressive and are often accompanied by lymph node (LN) metastasis, a high recurrence rate, and poor prognosis. Distinguishing highly invasive metastatic PTC is an urgent problem that needs to be addressed clinically. We analyzed a microarray of metastasized PTC and validated it using quantitative reverse transcription PCR (RT-qPCR) and immunohistochemistry to identify biomarkers that can be used to assess the risk of PTC metastasis.</p></sec><sec><title>Methods</title><p>The microarray of metastasized PTC was screened using the Gene Expression Omnibus (GEO) database. The differences between cancer and normal tissues were analyzed using the official GEO tool: GEO2R. Gene expression profile data (GEPIA) were used to verify the expression of differential genes in large samples and to analyze their correlation. The Kaplan–Meier plotter (KM-plotter) database was used for the analysis of genes potentially related to survival. RT-qPCR was used to check the expression of risk factor genes in pathological sections from PTC patients with clinical LN metastasis. Immunohistochemistry was used to verify the expression of core risk-associated genes.</p></sec><sec><title>Results</title><p>Fourteen PTC metastasis-associated genes were identified. In metastasized PTC, <italic>CLDN1</italic>, <italic>LRP4</italic>, <italic>LRRK2</italic>, and <italic>TENM1</italic> were highly expressed, whereas <italic>DIO1</italic>, <italic>DPP6</italic>, <italic>HGD</italic>, <italic>IPCEF1</italic>, <italic>MT1F</italic>, <italic>SLC26A4</italic>, <italic>SLC26A7</italic>, <italic>SPX</italic>, <italic>TFF3</italic>, and <italic>TPO</italic> were expressed at low levels, compared to expression in normal tissues. <italic>DIO1</italic>, <italic>HGD</italic>, <italic>SLC26A4</italic>, and <italic>TPO</italic> were found to be the core risk genes in the PTC metastatic risk set. Results based on clinical samples showed that the expression differences for metastasis risk-associated genes were consistent with the bioinformatics analysis results.</p></sec><sec><title>Conclusions</title><p>Fourteen differentially expressed genes (<italic>CLDN1</italic>, <italic>LRP4</italic>, <italic>LRRK2</italic>, <italic>TENM1</italic>, <italic>DIO1</italic>, <italic>DPP6</italic>, <italic>HGD</italic>, <italic>IPCEF1</italic>, <italic>MT1F</italic>, <italic>SLC26A4</italic>, <italic>SLC26A7</italic>, <italic>SPX</italic>, <italic>TFF3</italic>, <italic>TPO</italic>) are associated with an increased risk of PTC metastasis, and <italic>DIO1</italic>, <italic>HGD</italic>, <italic>SLC26A4</italic>, and <italic>TPO</italic> are the key risk-associated genes in this set that might affect the occurrence and development of PTC through iodine metabolism. These genes could provide a reference for clinical metastatic PTC risk evaluation and treatment.</p></sec>