Key Signaling Pathways Influenced by microRNA and the Potential Genes Implicated
| Signaling Pathways* | # of Genes Implicated |
|---|---|
| MAPK | 1426 |
| AKT | 22-300+7,8 |
| PI3K | 3428 |
| JAK/STAT | 119 |
| DICER 1 | 110 |
| Wnt/β-Catenin | 1911 |
| ERK | Potentially thousands12 |
| Adipocytokine | 3213 |
| TGFβ | 3314 |
The microRNAs evaluated by ThyraMIRv2 help provide insight into signaling pathways encompassing at least these 602 genes, and potentially thousands more. The combination testing approach of the ThyGeNEXT+ ThyraMIRv2 testing platform utilizes both mutational analysis and microRNA signatures to provide deep insight into indeterminate thyroid nodules, helping to enhance confidence in clinical decision-making.
Why This Matters
microRNAs are referred to as master regulators of gene expression, influencing the types and amounts of proteins made by cells.15 microRNAs regulate transcription and can also activate translation, orchestrating the development of cells as well as cell differentiation, proliferation, apoptosis, and tumor growth.15,16,17
What makes microRNA analysis particularly valuable is its dynamic network of control. A single microRNA can regulate multiple different genes, and conversely, each gene can be regulated by several microRNAs.18
This is especially relevant in thyroid cancer, because thyroid cancer develops through complex genetic alterations across multiple signaling pathways. Researchers have acknowledged that changes in gene expression within pathways, like MAPK, can contribute to tumor development.19 By analyzing a broad set of genes within these signaling pathways, the microRNA assessment can help identify molecular patterns associated with malignancy that mutation-only tests might miss.
Clinical Impact
By combining mutational and microRNA analysis, the ThyGeNEXT+ThyraMIRv2 test provides a unique risk assessment of indeterminate thyroid nodules. The microRNAs assessed by ThyraMIRv2 can play a role in both major and minor signaling pathways, potentially helping to provide insight into at least 602 genes. This can help improve diagnostic sensitivity and specificity when distinguishing between benign and malignant thyroid nodules.3,19 microRNA analysis obtained by the ThyraMIRv2 test, in combination with the ThyGeNEXT oncogene panel results, has been shown to provide accurate risk stratification of indeterminate thyroid nodules, providing confidence in clinical decision-making.
ThyGeNEXT+ThyraMIRv2 evaluates both microRNA signaling pathways and mutations to risk-stratify indeterminate thyroid nodules with high NPV, PPV, and BCR performance.
FAQs
How does ThyGeNEXT+ThyraMIRv2 help improve risk stratification of indeterminate thyroid nodules?
Which signaling pathways does the ThyraMIRv2 panel evaluate?
The ThyraMIRv2 panel evaluates both major and minor signaling pathways influenced by microRNA and helps provide insight into their associated genes.3-5
- MAPK – 142 genes11
- AKT – 22-300+ genes11,13
- PI3K – 342 genes13
- JAK/STAT – 11 genes14
- DICER 1 – 1 gene15
- Wnt/β-Catenin – 19 genes16
- ERK – potentially thousands of genes17
- Adipocytokine – 32 genes18
- TGFβ – 33 genes19
How does ThyraMIRv2 provide insight into gene expression across multiple signaling pathways?
ThyraMIRv2 analyzes microRNA signatures. microRNAs are the master regulators of gene expression, including the regulation of both major and minor signaling pathways involved in the development of thyroid cancer (ie, MAPK, PI3K/AKT, and RET).3 By evaluating the regulators of these important signaling pathways, ThyraMIRv2 can identify molecular patterns associated with malignancy that mutation-only tests might miss.
Patient management decisions are based on the independent medical judgment of the physician and molecular test results should be taken into consideration in conjunction with all relevant imaging, clinical findings, patient and family history, as well as patient preference.
*miR-375, AKT, ERK, PI3K; miR-222, Adipocytokine, JAK/STAT signaling pathway; miR-146b, DICER1 pathway, Wnt/β-Catenin pathway; miR-21, PI3K-AKT; miR-139, MAPK, PI3K; miR-29, TGF-β, Wnt, PI3K-AKT. This listing of microRNA markers is not fully inclusive of all the microRNAs assessed by ThyraMIRv2.
References: 1. Finkelstein SD, et al. Thyroid. 2022;32(11):1362-1371. 2. Lupo MA, et al. Diagn Cytopathol. 3. Ghafouri-Fard S, et al. Noncoding RNA Res. 2020;5(3):88-98. 4. Bonneau E, et al. EJIFCC. 2019;30(2):114-127. 5. Wylie D, et al. J Pathol Clin Res. 2016;2(2):93-103. 6. Sinkala M, et al. Commun Biol. 2021;4(1):9. 7. Catasus L, et al. Mod Pathol. 2010;23(5):694-702. 8. Slattery ML, et al. Mol Carcinog. 2018;57(2):243-261. 9. Hu X, et al. Signal Transduct Target Ther. 2021;6(1):402. 10. Vergani-Junior CA, et al. Biophys Rev. 2021;13(6):1081-1090. 11. Driehuis E, et al. Br J Pharmacol. 2017;174(24):4547-4563. 12. Chen JY, et al. Cell Rep. 2023;42(3):112252. 13. Apio C, et al. Front Endocrinol (Lausanne). 2023;14:1165744. 14. Morikawa M, et al. Cold Spring Harb Perspect Biol. 2016;8(5):a021873. 15. O’Brien J, et al. Front Endocrinol (Lausanne). 2018;9:402. 16. Oliveto S, et al. World J Biol Chem. 2017;8(1):45-56.. 17. Lee JC, et al. Oncologist. 2014;19(11):1141-1147. 18. Press release. NobelPrize.org. Nobel Prize Outreach AB 2025. Accessed Jan 22, 2025. https://www.nobelprize.org/prizes/medicine/2024/press-release/ 19. Pupin B, et al. Biomedicines. 2025;13(7):1577. https://www.mdpi.com/2227-9059/13/7/1577.
THY-0281-002-0825