Driver Genes of Locally Advanced Well-differentiated Thyroid Cancer: Genetic Landscape Based on the TCGA Database
Abstract 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 the driver genes of locally advanced WDTC by analyzing the TCGA cohort.Methods: We analyzed data on 501 patients with WDTC from the TCGA cohort. Patients were classified into two subgroups of pathological T4 stage or T1-3 stage (Cluster1 and Cluster2, respectively). The mRNA expression differences between subgroups were compared for several genes in the TCGA cohorts.Results: Cluster1 included 23 patients with pathological T4 classification (Papillary=21/Follicular=2) and Cluster2 included 478 patients (Papillary=371/Follicular=100/Others=7). The Cluster1 subgroup showed worse overall survival than the Cluster2 subgroup (p < 0.05). The two subgroups were analyzed for 34 genes reported in previous studies. Known genetic thyroid cancer alterations, including BRAF, RAS, RET, and ALK, were not different in the two subgroups. In Cluster1, 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 compared with the Cluster2 (all, 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 the 16 genetic markers.Conclusions: Locally advanced WDTC presented 16 genetic alterations compared to less aggressive thyroid cancers. Somatic mutations associated with local invasion transformation were identified. Genetic profiles associated with locally advanced WDTC have prognostic significance, but these findings must be validated to further understand the pathway..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
ResearchSquare.com - (2022) vom: 09. März Zur Gesamtaufnahme - year:2022 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Jung, Ah Ra [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| doi: |
10.21203/rs.3.rs-582794/v1 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XRA033988285 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XRA033988285 | ||
| 003 | DE-627 | ||
| 005 | 20230429200929.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 220113s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.21203/rs.3.rs-582794/v1 |2 doi | |
| 035 | |a (DE-627)XRA033988285 | ||
| 035 | |a (ResearchSquare)10.21203/rs.3.rs-582794/v1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | |a 570 |q DE-84 | |
| 100 | 1 | |a Jung, Ah Ra |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Driver Genes of Locally Advanced Well-differentiated Thyroid Cancer: Genetic Landscape Based on the TCGA Database |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract 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 the driver genes of locally advanced WDTC by analyzing the TCGA cohort.Methods: We analyzed data on 501 patients with WDTC from the TCGA cohort. Patients were classified into two subgroups of pathological T4 stage or T1-3 stage (Cluster1 and Cluster2, respectively). The mRNA expression differences between subgroups were compared for several genes in the TCGA cohorts.Results: Cluster1 included 23 patients with pathological T4 classification (Papillary=21/Follicular=2) and Cluster2 included 478 patients (Papillary=371/Follicular=100/Others=7). The Cluster1 subgroup showed worse overall survival than the Cluster2 subgroup (p < 0.05). The two subgroups were analyzed for 34 genes reported in previous studies. Known genetic thyroid cancer alterations, including BRAF, RAS, RET, and ALK, were not different in the two subgroups. In Cluster1, 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 compared with the Cluster2 (all, 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 the 16 genetic markers.Conclusions: Locally advanced WDTC presented 16 genetic alterations compared to less aggressive thyroid cancers. Somatic mutations associated with local invasion transformation were identified. Genetic profiles associated with locally advanced WDTC have prognostic significance, but these findings must be validated to further understand the pathway. | ||
| 700 | 1 | |a Jang, Dong Hyuk |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Jung Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Yoon Se |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t ResearchSquare.com |g (2022) vom: 09. März |
| 773 | 1 | 8 | |g year:2022 |g day:09 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.21203/rs.3.rs-582794/v1 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XRA | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |j 2022 |b 09 |c 03 | ||
| 953 | |2 045F |a 570 | ||