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

Abstract

BackgroundAlthough 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.MethodsThe 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.ResultsFourteen PTC metastasis-associated genes were identified. In metastasized PTC, CLDN1, LRP4, LRRK2, and TENM1 were highly expressed, whereas DIO1, DPP6, HGD, IPCEF1, MT1F, SLC26A4, SLC26A7, SPX, TFF3, and TPO were expressed at low levels, compared to expression in normal tissues. DIO1, HGD, SLC26A4, and TPO 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.ConclusionsFourteen differentially expressed genes (CLDN1, LRP4, LRRK2, TENM1, DIO1, DPP6, HGD, IPCEF1, MT1F, SLC26A4, SLC26A7, SPX, TFF3, TPO) are associated with an increased risk of PTC metastasis, and DIO1, HGD, SLC26A4, and TPO 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.

An oxidative stress-related lncRNA prognostic risk model for thyroid cancer

“…Moreover, we found that DPP6 connected THCA risk mRNA and protective mRNA. A study showed that DPP6 was expressed at low levels in metastatic PTC tissues compared with normal thyroid tissue [47], which can be considered as a protective factor, although be not entirely consistent with our ndings. Mutations of BRAF and RAS genes are mature molecular markers in THCA and have high evaluation value for the diagnosis and prognosis of THCA [48].…”

Risk factors analysis of lateral cervical lymph node metastasis in papillary thyroid carcinoma: a retrospective study of 830 patients

“…For most PTC patients, the 10-year overall survival rate after surgical resection, radioiodine therapy, and endocrine suppression therapy was 94.8% [ 28 ]. The malignant degree of PTC is low and the prognosis is good, but the cervical lymph node metastasis is easy to occur [ 29 ], and it is closely related to the increased risk of local recurrence [ 30 ]. Sapuppo et al found that the presence of lateral cervical lymph node metastasis was an important factor for postoperative recurrence and distant metastasis [ 31 ].…”

Exploration and validation of key genes associated with early lymph node metastasis in thyroid carcinoma using weighted gene co-expression network analysis and machine learning

“…In the case of THCA, several known risk factors have been linked to LNM, such as patient age, sex, multifocality, calcification, and extrathyroidal extension (ETE) (5,(10)(11)(12). In addition to established clinical factors, there has been a burgeoning interest in exploring genetic variations associated with LNM in recent years (13,14). For example, experimental evidence from both in vitro and in vivo studies has demonstrated that the upregulation of lnc-MPEG1-1:1 in papillary thyroid cancer (PTC) cell lines can elevate cell proliferation and migration (15).…”