Payva Febby, K S Santhy, James Remya, E Amrisa Pavithra, Sivaramakrishnan Venketesh
Department of Zoology, St. Joseph's College for Women, Alappuzha, Kerala, 688001, India.
Department of Zoology, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, Tamil Nadu, 641043, India.
Thyroid Res. 2025 Apr 11;18(1):15. doi: 10.1186/s13044-025-00230-1.
Papillary thyroid cancer (PTC) is the most prevalent follicular cell-derived subtype of thyroid cancer. A systems biology approach to PTC can elucidate the mechanism by which molecular components work and interact with one another to decipher a panoramic view of the pathophysiology.
PTC associated genes and transcriptomic data were retrieved from DisGeNET and Gene Expression Omnibus database respectively. Published proteomic and metabolomic datasets in PTC from EMBL-EBI were used. Gene Ontology and pathway analyses were performed with SNPs, differentially expressed genes (DEGs), proteins, and metabolites linked to PTC. The effect of a nucleotide substitution on a protein's function was investigated. Additionally, significant transcription factors (TFs) and kinases were identified. An integrated strategy was used to analyse the multi-omics data to determine the key deregulated pathways in PTC carcinogenesis.
Pathways linked to carbohydrate, protein, and lipid metabolism, along with the immune response, signaling, apoptosis, gene expression, epithelial-mesenchymal transition (EMT), and disease onset, were identified as significant for the clinical and functional aspects of PTC. Glyoxylate and dicarboxylate metabolism and citrate cycle were the most common pathways among the PTC omics datasets. Commonality analysis deciphered five TFs and fifty-seven kinases crucial for PTC genesis and progression. Core deregulated pathways, TFs, and kinases modulate critical biological processes like proliferation, angiogenesis, immune infiltration, invasion, autophagy, EMT, and metastasis in PTC.
Identified dysregulated pathways, TFs and kinases are critical in PTC and may help in systems level understanding and device specific experiments, biomarkers, and drug targets for better management of PTC.
甲状腺乳头状癌（PTC）是甲状腺癌中最常见的滤泡细胞源性亚型。采用系统生物学方法研究PTC，可阐明分子成分发挥作用及相互作用的机制，从而解读其病理生理学全景。
分别从DisGeNET和基因表达综合数据库（Gene Expression Omnibus）检索PTC相关基因和转录组数据。使用了欧洲生物信息研究所（EMBL-EBI）发布的PTC蛋白质组学和代谢组学数据集。对与PTC相关的单核苷酸多态性（SNP）、差异表达基因（DEG）、蛋白质和代谢物进行基因本体论和通路分析。研究了核苷酸取代对蛋白质功能的影响。此外，还鉴定了重要的转录因子（TF）和激酶。采用综合策略分析多组学数据，以确定PTC致癌过程中关键的失调通路。
与碳水化合物、蛋白质和脂质代谢以及免疫反应、信号传导、细胞凋亡、基因表达、上皮-间质转化（EMT）和疾病发生相关的通路，被确定为对PTC的临床和功能方面具有重要意义。乙醛酸和二羧酸代谢以及柠檬酸循环是PTC组学数据集中最常见的通路。共性分析解读出5个对PTC发生和进展至关重要的转录因子和57种激酶。核心失调通路、转录因子和激酶调节PTC中增殖、血管生成、免疫浸润、侵袭、自噬、EMT和转移等关键生物学过程。
所确定失调的通路、转录因子和激酶在PTC中至关重要，可能有助于从系统层面理解，并开展针对特定设备的实验、生物标志物和药物靶点研究，以更好地管理PTC。
