Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Cohort
2.2. RNA Isolation and Library Preparation
2.3. Variant Calling and Gene Expression Analysis
2.4. Fusion Gene Analysis
2.5. Confirmation of Selected Variants by Sanger Sequencing
2.6. Sample Cluster Analysis
2.7. BRAF V600E-RAS Score (BRS)
2.8. Thyroid Differentiation Score (TDS) and ERK Score
2.9. TMB Calculation
2.10. Differential Gene Expression Analysis
2.11. Differential Expression Analysis on PTC from the TCGA Cohort
2.12. Pathway Enrichment Analysis
2.13. Evaluation of Tumor-Infiltrating Immune Cells
2.14. Statistics
3. Results
3.1. RNA-Sequencing Framework
3.2. Identification of Novel Mutations in Thyroid Cancer
3.3. Gene Fusions in Thyroid Cancer
3.4. Technical and Experimental Validation by Sanger
3.5. In Silico Analysis
3.6. Negative Tumors Have Distinctive Expression Profiles
3.7. Negative BL Tumors Have Lower TMB Compared to Negative RL
3.8. Identification of Differentially Expressed Genes
3.9. Negative BL Tumors Have a High Expression of Immune System Components
3.10. Cancer-Related Pathways Are Differently Regulated in Negative BL and RL Tumors
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Sample | Tumor Type | Mutational Status | Expression Classifier Group | Gender | Age at Surgery | Tumor Size | Multifocality | ETE | Vascular Invasion | Lymph Node Metastasis | Stage | Risk |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | FVPTC | Negative | Negative RL | F | 45 | 3.0 | N | N | N | N | I | Low |
2 | FVPTC | Negative | Negative RL | F | 31 | 3.2 | N | N | Y | Y | I | High |
3 | FVPTC | Negative | Negative BL | F | 76 | 1.0 | Y | N | N | Y | II | High |
4 | FVPTC | Negative | - | F | 68 | 8.0 | Y | Y | Y | N | IVA | High |
5 | FVPTC | Negative | Negative RL | F | 52 | 0.9 | N | N | N | N | I | Low |
6 | FVPTC | Positive | RAS/PAX8-PPARg | M | 68 | 7.5 | N | N | N | N | II | High |
7 | FVPTC | Positive | RAS/PAX8-PPARg | F | 53 | 4.0 | Y | N | N | N | I | Low |
8 | FVPTC | Negative | Negative BL | M | 40 | 8.5 | Y | N | Y | Y | I | High |
9 | FVPTC | Negative | Negative RL | F | 73 | 1.2 | Y | N | N | N | I | Low |
10 | CVPTC | Negative | Negative BL | F | 59 | 2.5 | Y | N | N | N | I | Low |
11 | CVPTC | Positive | BRAF V600E | F | 46 | 1.7 | N | Y | Y | Y | I | High |
12 | CVPTC | Positive | BRAF V600E | F | 41 | 1.3 | N | N | N | N | I | Low |
13 | CVPTC | Negative | Negative RL | F | 56 | 3.0 | Y | Y | N | Y | III | High |
14 | FVPTC | Positive | RAS/PAX8-PPARg | M | 32 | 5.0 | N | Y | N | N | I | High |
15 | FVPTC | Positive | RAS/PAX8-PPARg | M | 40 | 4.0 | N | N | N | N | I | Low |
16 | FVPTC | Positive | RAS/PAX8-PPARg | F | 28 | 5.0 | Y | N | N | N | I | Low |
17 | FVPTC | Positive | RAS/PAX8-PPARg | F | 55 | 1.7 | Y | N | N | N | I | Low |
18 | FVPTC | Positive | RAS/PAX8-PPARg | F | 36 | 3.0 | N | N | N | N | I | Low |
19 | FVPTC | Positive | RAS/PAX8-PPARg | F | 45 | 1.1 | N | N | N | N | I | Low |
20 | FTC | Positive | RAS/PAX8-PPARg | F | 45 | 3.5 | Y | Y | N | N | II | High |
21 | FTC | Positive | RAS/PAX8-PPARg | F | 48 | 3.2 | N | N | Y | N | I | High |
22 | FTC | Positive | RAS/PAX8-PPARg | F | 48 | 1.6 | N | Y | Y | N | I | High |
23 | FTC | Negative | Negative BL | F | 35 | 4.5 | N | N | N | N | I | Low |
24 | FTC | Positive | RAS/PAX8-PPARg | F | 76 | 7.5 | N | Y | Y | Y | IVA | High |
25 | FTC | Positive | RAS/PAX8-PPARg | M | 70 | 10.3 | N | Y | Y | Y | IVA | High |
26 | FTC | Positive | RAS/PAX8-PPARg | F | 70 | 10.0 | N | N | N | N | II | High |
27 | FTC | Negative | Negative RL | F | 60 | 2.5 | Y | N | Y | N | IVA | High |
28 | HCC | Negative | Negative (HCC) | M | NA | NA | NA | NA | NA | NA | NA | NA |
29 | HCC | Negative | Negative (HCC) | F | 70 | 5.0 | N | N | Y | Y | IVA | High |
30 | HCC | Negative | Negative (HCC) | F | 63 | 6.0 | N | N | Y | N | IVA | High |
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Bim, L.V.; Carneiro, T.N.R.; Buzatto, V.C.; Colozza-Gama, G.A.; Koyama, F.C.; Thomaz, D.M.D.; de Jesus Paniza, A.C.; Lee, E.A.; Galante, P.A.F.; Cerutti, J.M. Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers. Cancers 2021, 13, 5184. https://doi.org/10.3390/cancers13205184
Bim LV, Carneiro TNR, Buzatto VC, Colozza-Gama GA, Koyama FC, Thomaz DMD, de Jesus Paniza AC, Lee EA, Galante PAF, Cerutti JM. Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers. Cancers. 2021; 13(20):5184. https://doi.org/10.3390/cancers13205184
Chicago/Turabian StyleBim, Larissa Valdemarin, Thaise Nayane Ribeiro Carneiro, Vanessa Candiotti Buzatto, Gabriel Avelar Colozza-Gama, Fernanda C. Koyama, Debora Mota Dias Thomaz, Ana Carolina de Jesus Paniza, Eunjung Alice Lee, Pedro Alexandre Favoretto Galante, and Janete Maria Cerutti. 2021. "Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers" Cancers 13, no. 20: 5184. https://doi.org/10.3390/cancers13205184