Abstract
The oncogenesis and progression of thyroid cancer (THCA) involve multiple pathways. Identification of potential interaction mechanisms of pathways related to the pathogenesis of THCA is key to the accuracy of diagnosis and treatment. We selected 8 FDA-approved drugs for THCA and identified 18 key genes (KGs) and 6 key pathways (KPs) by a comprehensive analysis of 116 drug-target genes and 153 disease genes. Then, bio-enrichment analysis of KGs was performed to determine dysfunction pathways mainly involved in THCA and crosstalk analysis of KPs was carried out to find the interaction of pathways. It was found that abnormal activation of receptor tyrosine kinase (RTK) can activate the entire pathway crosstalk mechanism, which is also the key of targeted therapy. Integrin can activate the focal adhesion and PI3K-Akt pathways, and further affect cancer migration. Activations of Ras, Rap1 and focal adhesion pathways cause over-activation of the downstream MAPK and PI3K-Akt pathways resulting in the tumor deterioration. Genetic alterations of receptors in EGFR tyrosine kinase inhibitor resistance pathway over-activate downstream MAPK and PI3K-Akt pathways, which promote the proliferation and differentiation of cancer cells. The close cooperation of these pathways promotes the cancer progression and metastasis, and is also of great value for the disease diagnosis and the development of combination therapies.
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Abbreviations
- ATC:
-
Anaplastic thyroid cancer.
- DEG:
-
Differentially expressed mRNA.
- EW:
-
Edge with weight.
- GEF:
-
Guanine nucleotide exchange factors.
- JC:
-
Jaccard coefficient.
- KGs:
-
Key genes.
- KPs:
-
Key pathways.
- OC:
-
Overlap coefficient.
- PIP2:
-
Phosphatidylinositol-4, 5-bisphosphate.
- PIP3:
-
Phosphatidylinositol-3, 4, 5-triphosphate.
- PTC:
-
Papillary thyroid cancer.
- RBD:
-
Raf binding domain.
- RTK:
-
Receptor tyrosine kinase.
- SEER:
-
Surveillance, Epidemiology, and End Results.
- SRE:
-
Serum response element.
- SRF:
-
Serum response factor.
- THCA:
-
Thyroid cancer
- TK:
-
Tyrosine kinase.
- UGT1A1:
-
UDP-glucuronyltransferase.
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This work was supported by the National Nature Science Foundation of China (grant numbers 21541006), Open Funding Project of the State Key Laboratory of Biocatalysis and Enzyme Engineering, and Research Projects of Wuxi health commission (No.MS201903).
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Weishan Han: Conceptualization, Methodology, Data Curation, Visualization, Writing - Original Draft, Writing- Reviewing and Editing; Yanyan Wu: Investigation; Xiaxia Wang: Software; Li Liu: Data analysis, Funding acquisition; Yanrui Ding: Supervision, Project administration, Funding acquisition.
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Han, W., Wu, Y., Wang, X. et al. Dissecting the critical pathway crosstalk mechanisms of thyroid cancer based on drug-target genes and disease genes. Biologia 76, 3489–3499 (2021). https://doi.org/10.1007/s11756-021-00869-9
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DOI: https://doi.org/10.1007/s11756-021-00869-9