Seven Genes Associated With Lymphatic Metastasis in Thyroid Cancer That Is Linked to Tumor Immune Cell Infiltration.

Linfeng Wu,Jiaohao Cai,Weike Chen,Xiaogang Zhang,Chao Chen,Guanli Huang,Ziliang Qian,Yaoyao Guan,Mengmeng Zheng,Yuying Zhou,Shurong Shen,Rongyao Xiao,Kaiting Sun

doi:10.3389/fonc.2021.756246

Abstract

ObjectiveSince there are few studies exploring genes associated with lymphatic metastasis of thyroid carcinoma (THCA), this study was conducted to explore genes associated with lymphatic metastasis of THCA and to investigate the relationship with immune infiltration.MethodsDifferentially expressed genes associated with THCA lymphatic metastasis were analyzed based on The Cancer Genome Atlas Program (TCGA) database; a protein-protein interaction(PPI)network was constructed to screen for pivotal genes. Based on the identified hub genes, their expression in THCA with and without lymphatic metastasis were determined. Functional enrichment analysis was performed. The correlation between the identified genes and immune cell infiltration was explored. LASSO logistic regression analysis was performed to determine the risk score of the most relevant gene constructs and multifactor COX regression analysis based on genes in the risk score formula.ResultsA total of 115 genes were differentially expressed in THCA with and without lymphatic metastasis, including 28 upregulated genes and 87 downregulated genes. The PPI network identified seven hub genes (EVA1A, TIMP1, SERPINA1, FAM20A, FN1, TNC, MXRA8); the expression of all seven genes was upregulated in the group with lymphatic metastasis; Immuno-infiltration analysis showed that all seven genes were significantly positively correlated with macrophage M1 and NK cells and negatively correlated with T-cell CD4+ and myeloid dendritic cells. LASSO logistic regression analysis identified the five most relevant genes (EVA1A, SERPINA1, FN1, TNC, MXRA8), and multi-factor COX regression analysis showed EVA1A, SERPINA1 and FN1 as independent prognostic factors.ConclusionSeven genes were associated with lymphatic metastasis of THCA and with tumor immune cell infiltration.

Highlights

Thyroid carcinoma (THCA) is the most prevalent endocrine cancer worldwide
The PPI network identified seven hub genes (EVA1A, TIMP1, SERPINA1, FAM20A, FN1, TNC, MXRA8); the expression of all seven genes was upregulated in the group with lymphatic metastasis; Immuno-infiltration analysis showed that all seven genes were significantly positively correlated with macrophage M1 and NK cells and negatively correlated with T-cell CD4+ and myeloid dendritic cells
Seven genes were associated with lymphatic metastasis of THCA and with tumor immune cell infiltration

Summary

Introduction

Thyroid carcinoma (THCA) is the most prevalent endocrine cancer worldwide. It usually presents as a neck mass and causes dysphagia, dysphonia or hoarseness, stridor, and dyspnea due to its occupying effect on the esophagus and trachea [1, 2]. The rising incidence of THCA has had a significant impact on the elderly population, as adults aged 65 years and above have experienced the greatest increase in THCA incidence and the greatest change in cancer prognosis. This further leads to a greater risk of THCA treatment as well, due to lower renal clearance, increased likelihood of radioiodine overtreatment, and increased risk of arrhythmias and bone loss due to suppressive doses of thyroid hormone replacement [4]. With the emergence of new effective therapies, drugs have been developed to play an important role in inhibiting tumor lymphatic metastasis by targeting biomarkers and . The present study, explores genes that may affect lymphatic metastasis of THCA based on comprehensive bioinformatics analysis and investigates their relationship with immune infiltration to provide new ideas for the clinical treatment of lymphatic metastasis of THCA

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Results

Conclusion