| Research background:Thyroid cancer is the most common endocrine malignancy,and its incidence continues to rise in recent years,which is much higher than other tumors.The common classification types of thyroid cancer are PTC、FTC、MTC and ATC.The most common of the above-mentioned types of thyroid cancer is PTC,accounting for more than 80%.Although PTC is an inert tumor with low malignancy and can have a very good prognosis after conventional surgical treatment,some patients still have tumor invasion,lymph node metastasis,incomplete surgical resection,abnormal postoperative iodine uptake and other high risk factors affecting prognosis.Therefore,it is necessary to explore new biomarkers and potential therapeutic targets to optimize preoperative diagnosis,evaluate disease progression and improve disease prognosis.Further understanding of the biological behavior of PTC is conducive to providing better diagnosis and treatment for PTC.The E2F family is a group of genes encoding transcription factors in higher eukaryote,which contributes effectively to mammalian cell cycle regulation and DNA synthesis.Numerous studies have demonstrated that E2Fs are closely associated with many cancers.Research objectives:The expression of E2F family genes in papillary thyroid carcinoma was explored by biological analysis method,and the relationship between dysregulated expression and papillary thyroid carcinoma and clinicopathological characteristics was analyzed,so as to provide theoretical basis for finding new biomarkers and therapeutic targets.Material and methods:The original data of PTC patients were downloaded from The Cancer Genome Atlas(TCGA)database and analyzed after screening.Meanwhile,Kaplan-Meier curve was used to compare and analyze the correlation between E2Fs family and The clinicopathological characteristics of PTC.Subsequently,matched tumor tissue samples and paracancerous normal tissue samples were collected from 80 patients with papillary thyroid carcinoma who underwent surgery in the First Affiliated Hospital of Zhengzhou University.Immunohistochemical experiments were conducted to verify the relationship between the expression level of E2FS in thyroid cancer and normal thyroid tissue and clinicopathological features.In addition,GO functional enrichment analysis and KEGG pathway analysis were performed by Metscape.Results:Data analysis in the TCGA database showed that the expression level of E2FS mRNA was significantly changed in PTC patients,and the expression levels of E2F1,7,and 8 in tumor tissues were higher than that in paracancerous normal thyroid tissues,and the expression levels of E2F7 and E2F8 were significantly increased compared with that in paracancerous normal tissues,with statistical significance(P<0.01).The expression of E2F4 was reversed,and its expression level was higher in normal tissues(P<0.05).The correlation between E2F2 and E5 and clinicopathological features was correlated with tumor stage(P<0.05).In addition,Kaplan-Meier analysis confirmed that higher levels of E2F1,2,7,and 8 were associated with poorer relapse-free survival in thyroid cancer patients(P<0.05).IHC validation results also proved that the expression levels of E2F1,7 and 8 in tumor tissues were higher than those in adjacent normal tissues(P<0.05),while E2F4 was the opposite.E2F1,7,and 8 were correlated with lymph node metastasis and extratumoral invasion(P<0.05).ROC analysis showed that the AUC of E2F1 was 0.936(95%CI=0.890 to 0.982;P<0.001).AUC of E2F7 was 0.815(95%CI=0.734 to 0897;P<0.001).AUC of E2F81 was 0.725(95%CI=0.625 to 0.825;P<0.001).Finally,GO and KEGG analysis showed that the concentration was mainly in cell cycle,chromosome segregate and DNA replication.Conclusion:1.High E2F1,7,and 8 expressions could also serve as molecular markers to identify high-risk subgroups of patients with thyroid cancer.2.E2F2、5 are related to tumor stage,so it may be used to determine thyroid cancer prognosis.3.Our findings suggested that E2F1,2,7,and 8 were potential therapeutic targets for thyroid cancer,and transcriptional E2F4 was potential prognostic markers for the improvement of thyroid cancer survival and prognosis. |
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