Integrated transcriptome sequencing and weighted gene co-expression network analysis reveals key genes of papillary thyroid carcinomas.

OBJECTIVE: Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancers and has a high recurrence rate. We aimed to screen key genes involved in PTC to provide novel insights into the mechanisms of PTC.

METHODS: Seven microarray datasets of PTC were downloaded from gene expression omnibus database. Differentially expressed genes (DEGs) between PTC and normal samples were screened in the merged dataset. Then, protein-protein interaction (PPIs) functional modules analysis and weighted gene co-expression network analysis (WGCNA) were utilized to identify PTC-associated key genes. The identified key genes were then characterized from various aspects, including gene set enrichment analysis (GSEA) and the associations with immune infiltration, methylation levels and prognosis.

RESULTS: A large numbers of DEGs were identified, and these DEGs are involved in several cancer pathways. Nine key genes (including down-regulated genes GNA14, AVPR1A, and WFS1, and up-regulated genes LAMB3, PLAU, MET, MFGE8, PRSS23, and SERPINA1) were identified. Patients in the AVPR1A and GNA14 high expression groups had better disease-free survival (DFS) than those in the low expression group. Key genes were mainly involved in P53 pathway, estrogen response, apoptosis, glycolysis, NOTCH signaling, epithelial mesenchymal transition, WNT_beta catenin signaling, and inflammatory response. The expression of key genes was associated with immune cell infiltration and corresponding methylation levels. The verification results of key gene proteins and mRNA expression levels using external validation datasets were consistent with our expectations, implying the involvements of key genes in PTC.

CONCLUSION: The key genes may serve as potential therapeutic targets for PTC. This study provides novel insights into the mechanisms underlying PTC development.