| Thyroid carcinoma is the most common endocrine-related cancer worldwide.Papillary thyroid carcinoma(PTC) accounts for 80% of thyroid carcinoma. As sustained growth of PTC incidence, molecular markers is desirable to remedy the indefinite result of exsiting methods and indicate disease progression.Micro RNAs(mi RNAs) are non-protein-coding, endogenous small RNA molecules,playing essential roles in tumorgenesis and progression by combining to 3’UTR of target genes. In the present study, we analyzed expression profiles of mi RNAs and genes using 499 PTC samples and 58 normal thyroid tissues obtained from TCGA database. As a result, 82 differentially expressed mi RNAs and 2731 differentially expressed genes were identified. Among them, 82 genes were involved in tumor signaling pathway by KEGG Pathway method. A pivotal regulatory network of 18 mi RNAs and 20 targets in PTC was identified. In mi RNAs, up-regulating mi RNAs(mi R-222, i R-221, mi R-146 b, mi R-181a/b/d, mi R-34 a,mi R-424) and down-regulating mi RNAs(mi R-9-1, mi R-138, mi R-363, mi R-20 b, mi R-195 and mi R-152) were identified. Among them, up-regulating of mi R-424 and down regulating of mi R-363,mi R-195 and mi R-152 were novelly identified. In genes, up-regulating of CCNE2,E2F1, RARA, CCND1, RUNX1, ITGA2, MET, CDKN1 A, COL4A1 and down-regulating of AXIN2, TRAF6, BCL2, RARB, HSP90B1, FGF7 and PDGFRA were identified. Among them, CCNE2, COL4A1, TRAF6 and HSP90B1 were novelly identified.By performing ROC curves, several mi RNAs(up-regulating mi R-34 a, mi R-221,mi R-222, mi R-146 b, and down-regulating mi R-9-1, mi R-486, mi R-451, mi R-144,mi R-9-2, mi R-195) and genes(up-regulating CDKN2 B, CCND1, TGFA, ELFN1,BID, DVL1, BCL2L1, RARA, BAX, E2F1, PDGFA, RXRG, MET, LPAR5, ITGA2,and down-regulating BCL2, TRAF6, GLI1, KIT, LPAR1, WNT11, RARB, PRKX,FGFR2) display ideal diagnostic value higher than 90%, with sensitivity and specificity higher than 80%. Combination of inversely-expressed mi RNA and target improved diagnostic accuracy, particularly shown in mi R-34a/BCL2(sensitivity:98.4%; specificity: 98.1%).In clinical association analysis, we identified several mi RNAs and genes associated with progressive clinical features. Among 38 differentially expressed mi RNAs,mi R-146 b, mi R-222, mi R-21, mi R-375 and mi R-652 were associated with extrathyroidal extension, lymph node metastasis and high TNM stage, displaying potential roles in PTC risk stratification and prognosis. mi R-221, mi R-181a-1 and mi R-152 were associated with lymph node metastasis; mi R-221, mi R-34 a, mi R-424,mi R-138-1, mi R-138-2, mi R-20 b, mi R-152, mi R-486, mi R-451, mi R-153 and mi R-7-2 were associated with extrathyroidal extension; mii R-34 a, mi R-424,mi R-138-1, mi R-20 b, mi R-486, mi R-451 and mi R-7-2were associated with high TNM stage. Among 82 diferentially expressed genes,MET, TGFBR1, RARA, BAX,LAMC2, BCL2, PDGFRA, BCL2L1, TCF7L1, CDKN2 B, KIT, DAPK2, LPAR5,FGF11, PAX8, FGFR2, PRKACB, GNAI1, RUNX1, GNG7, TGFB1, HSP90B1,TRAF6, ITGA3 and LAMB3 were associated with extrathyroidal extension, lymph node metastasis and high TNM stage, displaying potential roles in PTC risk evaluation and prognosis. PTCH2, EGF, DVL1, ITGA2 B, PRKCA, RXRG, WNT3,AXIN2 and TGFA were associated with lymph node metastasis. DVL1, ITGA2, BID,FZD5, ITGA2 B, PTCH2, TGFA, AXIN2, CDKN1 A, RARB, WNT11, GLI3 and RUNX1T1 were associated with high TNM stage.In summary, our study analyzed a large number of PTC samples of TCGA dataset, identified expressing profiles of mi RNAs and genes in PTC, and accomplished regulatory network of mi RNAs and target genes involved in tumor signaling pathway. Many of them displayed potential diagnostic value and association with progressive clinical features. These moleculars show promising usein clinical practice for guiding diagnosis, risk stratification, treatment strategy and prognosis of thyroid carcinoma. |
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