Pan Lingfeng, Zhang Lianbo, Fu Jingyao, Shen Keyu, Zhang Guang
Department of Plastic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, China.
Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, China.
Heliyon. 2024 Mar 15;10(7):e27928. doi: 10.1016/j.heliyon.2024.e27928. eCollection 2024 Apr 15.
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.
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.
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.
The key genes may serve as potential therapeutic targets for PTC. This study provides novel insights into the mechanisms underlying PTC development.
甲状腺乳头状癌（PTC）占甲状腺癌的大多数，且复发率高。我们旨在筛选参与PTC的关键基因，为PTC的发病机制提供新的见解。
从基因表达综合数据库下载7个PTC的微阵列数据集。在合并数据集中筛选PTC与正常样本之间的差异表达基因（DEG）。然后，利用蛋白质-蛋白质相互作用（PPI）功能模块分析和加权基因共表达网络分析（WGCNA）来识别与PTC相关的关键基因。随后从多个方面对鉴定出的关键基因进行表征，包括基因集富集分析（GSEA）以及与免疫浸润、甲基化水平和预后的关联。
鉴定出大量DEG，这些DEG参与了多种癌症通路。鉴定出9个关键基因（包括下调基因GNA14、AVPR1A和WFS1，以及上调基因LAMB3、PLAU、MET、MFGE8、PRSS23和SERPINA1）。AVPR1A和GNA14高表达组患者的无病生存期（DFS）优于低表达组。关键基因主要参与P53通路、雌激素反应、凋亡、糖酵解、NOTCH信号传导、上皮-间质转化、WNT_β连环蛋白信号传导和炎症反应。关键基因的表达与免疫细胞浸润和相应的甲基化水平相关。使用外部验证数据集对关键基因蛋白和mRNA表达水平的验证结果与我们的预期一致，这表明关键基因参与了PTC的发生发展。
这些关键基因可能成为PTC的潜在治疗靶点。本研究为PTC发生发展的潜在机制提供了新的见解。
