2214P - Identification of prognosis-associated genes in locally advanced well-differentiated thyroid cancer using TCGA cohort analysis

Background

Despite the usually favorable prognosis of well-differentiated thyroid cancer (WDTC) following appropriate treatment, advanced T-staged WDTCs are associated with poor prognosis. This study focused on identifying genes associated with the prognosis of locally advanced WDTC by analyzing the TCGA cohort.

Methods

We analyzed data on 501 patients with WDTC and classified them into two subgroups: pathological T4 stage (Cluster1) or T1-3 stage (Cluster2). We compared the mRNA expression of thyroid cancer-related genes, and the somatic mutation frequency of various cancer genes between the two subgroups.

Results

Cluster1 included 23 patients (papillary = 21/follicular-variant of PTC = 2) and Cluster2 478 patients (papillary = 371/follicular-variant of PTC = 100/others = 7). Cluster1 showed worse overall and disease-free survival than Cluster2 (p < .05 and p = .12, respectively). Patients with pT4 stage had about a 1.8-fold increased risk of overall recurrence or death. MET, SERPINA1, TIMP1, PROS1, FN1, CDKN2A, and CDKN2B were significantly elevated while TG, DNAH9, TFF3, CRABP1, TPO, JAK2, KIT, KDR, and NFE2L2 were significantly lower in Cluster1 (all, p < 0.05 and adjusted p < 0.05). A TERT, EIF1AX, and ATM showed significantly frequent somatic mutations in Cluster1 compared to Cluster2. We also identified seven pathways related to 16 genetic markers.

Conclusions

Locally advanced WDTC presented 16 genetic alterations compared to less aggressive thyroid cancers. We identified somatic mutations associated with local invasion transformation. Relevant pathways related to the 16 genetic markers could be therapeutic targets. Genetic analysis of locally advanced WDTC may predict clinical applications in patient survival.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding

Disclosure

All authors have declared no conflicts of interest.