Genetic Analysis of Locally Advanced Well-Differentiated Thyroid Cancer: Clinical Prognostic Implications
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Background and Objectives Despite the usually favorable prognosis of well-differentiatedthyroid cancer (WDTC) following appropriate treatment, advanced T-staged WDTCs are as-sociated with poor prognosis. This study focused on identifying genes associated with theprognosis of locally advanced WDTC by analyzing a The Cancer Genome Atlas cohort. Subjects and Method We analyzed the data of 501 patients with WDTC and classifiedthem into two subgroups: pathological T4 stage (Cluster 1) or T1-3 stage (Cluster 2). We com-pared the mRNA expressions of thyroid cancer-related genes, and the somatic mutation fre-quencies of various cancer genes between the two subgroups. Results Cluster 1 included 23 patients (papillary=21/follicular-variant papillary thyroid can-cer [FVPTC]=2) and Cluster 2 478 patients (papillary=371/ FV PTC=10 0/ot her s=7). Cluster 1showed worse overall and disease-free survival than Cluster 2 ( p<0.05 and p=0.12 , respe c-tively). Patients with pT4 stage had about a 1.8-fold increased risk of overall recurrence ordeath. MET, SERPINA1, TIMP1, PROS1, FN1, CDKN2A, and CDKN2B were significantly ele-vated while TG, DNAH9, TFF3, CR A BP1, TPO, JAK2, KIT, KDR, and NFE2L2 were signifi-cantly lower in Cluster 1 (all, p<0.05 and adjusted p<0.05). A TERT, EIF1A X, and ATMshowed significantly frequent somatic mutations in Cluster 1 when compared to Cluster 2. Wealso identified seven pathways related to 16 genetic markers. Conclusion Locally advanced WDTC presented 16 genetic alterations. We identified so-matic mutations associated with local invasion transformation. Relevant pathways related tothe 16 genetic markers could be therapeutic targets. Genetic analysis of locally advancedWDTC may be used to predict clinical applications in patient survival.
Abstract
Background and Objectives Despite the usually favorable prognosis of well-differentiatedthyroid cancer (WDTC) following appropriate treatment, advanced T-staged WDTCs are as-sociated with poor prognosis. This study focused on identifying genes associated with theprognosis of locally advanced WDTC by analyzing a The Cancer Genome Atlas cohort. Subjects and Method We analyzed the data of 501 patients with WDTC and classifiedthem into two subgroups: pathological T4 stage (Cluster 1) or T1-3 stage (Cluster 2). We com-pared the mRNA expressions of thyroid cancer-related genes, and the somatic mutation fre-quencies of various cancer genes between the two subgroups. Results Cluster 1 included 23 patients (papillary=21/follicular-variant papillary thyroid can-cer [FVPTC]=2) and Cluster 2 478 patients (papillary=371/ FV PTC=10 0/ot her s=7). Cluster 1showed worse overall and disease-free survival than Cluster 2 ( p<0.05 and p=0.12 , respe c-tively). Patients with pT4 stage had about a 1.8-fold increased risk of overall recurrence ordeath. MET, SERPINA1, TIMP1, PROS1, FN1, CDKN2A, and CDKN2B were significantly ele-vated while TG, DNAH9, TFF3, CR A BP1, TPO, JAK2, KIT, KDR, and NFE2L2 were signifi-cantly lower in Cluster 1 (all, p<0.05 and adjusted p<0.05). A TERT, EIF1A X, and ATMshowed significantly frequent somatic mutations in Cluster 1 when compared to Cluster 2. Wealso identified seven pathways related to 16 genetic markers. Conclusion Locally advanced WDTC presented 16 genetic alterations. We identified so-matic mutations associated with local invasion transformation. Relevant pathways related tothe 16 genetic markers could be therapeutic targets. Genetic analysis of locally advancedWDTC may be used to predict clinical applications in patient survival.
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