شناسايي شبكه RNA درون زاد رقابتي LncRNA/circRNA/Pseudogene-miRNA-mRNA در سرطان تيروئيد پاپيلاري

Papillary thyroid carcinoma (PTC) is a malignancy whose etiology is not yet fully understood. The competitive endogenous RNA (ceRNA) hypothesis offers a model to better comprehend the molecular mechanisms driving carcinogenesis. This study aimed to construct a novel ceRNA network to identify reliable diagnostic an‎d prognostic indicators applicable across all stages of PTC. Transcriptome analysis identified differentially expressed genes (DEGs) common to all PTC stages compared to normal tissue. Key genes were subsequently screened using MCC, IVI, an‎d MCODE algorithms to construct a novel five-layer ceRNA network an‎d its associated DE-TF regulatory network. The diagnostic performance of elements within both networks was eva‎luated using Receiver Operating Characteristic (ROC) curves. Furthermore, a risk assessment model was developed by identifying key genes from the ceRNA an‎d DE-TF components through univariable Cox an‎d LASSO regression analyses. Findings were validated in tissue an‎d peripheral blood samples using RT-qPCR, an‎d correlations between gene expression an‎d blood calcium levels were investigated. The ceRNA an‎d DE-TF networks comprised 30 an‎d 22 components, respectively. Logistic regression analysis identified a panel of 8 genes (PKMYT1, E2F1, NFATC1, STAT6, E2F3, LINC02910, GAS5, an‎d TK1) as reliable diagnostic markers for PTC, achieving an AUC of 96.9%. Among these, PKMYT1 an‎d GAS5 were identified as stage-specific markers in tumor tissues, showing significant upregulation in High-Aggressive (HA) tumors compared to Low-Aggressive (LA) ones. These two genes demonstrated strong diagnostic value in differentiating HA from LA tumors, with AUCs of 0.81 an‎d 0.87, respectively. circMET, which was upregulated in both groups, showed potential in distinguishing LA tumors from adjacent normal tissues (AUC = 0.81). Non-invasive eva‎luation in peripheral blood revealed a distinct pattern, while GAS5 was downregulated, miR-3671 an‎d circMET were significantly upregulated in the HA group compared to the LA group, offering a meaningful profile for distinguishing disease progression stages. Additionally, GAS5 expression was associated with blood calcium levels. The SERN prognostic model, comprising STAT6, E2F1, RMI2, an‎d NR4A1, highlighted the significance of these genes as reliable prognostic markers for overall survival in PTC. In conclusion, PKMYT1, GAS5, an‎d circMET are significantly associated with PTC aggressiveness. PKMYT1 an‎d GAS5 serve as strong indicators for tumor aggression, while circMET is valuable for early detection, an‎d GAS5 correlates with physiological calcium levels.

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