载脂蛋白C1在甲状腺乳头状癌中的临床表达及生物信息学分析

Bioinformatics analysis of the clinical expression of APOC1 in papillary thyroid carcinoma

摘要:

目的 研究载脂蛋白C1（APOC1）在甲状腺乳头状癌（PTC）和癌旁（PC）组织的表达水平及临床意义。方法 利用UALCAN数据库比较PTC及PC组织APOC1 mRNA的表达差异；Kaplan-Meier Plotter数据库预测APOC1对PTC的预后价值；HPA数据库预测APOC1在蛋白层面的表达情况；TIMER数据库研究APOC1与免疫细胞的相关性；Linked Omics数据库和GeneMANIA数据库研究与APOC1密切相关的基因；GSCALite数据库对PTC中前5关键基因的药物靶标和癌症相关通路进行分析；最后对APOC1基因进行单基因GSEA分析。结果 PTC组织中APOC1 mRNA表达水平显著高于PC组织；APOC1 mRNA表达水平在不同临床分期、年龄、性别、淋巴结转移的PTC中显著升高；APOC1 mRNA表达水平与预后和免疫浸润相关；APOC1与多条癌症通路相关，并可受到abiraterone、GSK-J4、SR8278抑制调节；GSEA单基因的功能富集分析显示，APOC1功能富集在丙酸代谢、缬氨酸和异亮氨酸、三羧酸循环、牛磺酸代谢、JAK-STAT信号通路、自身免疫性甲状腺病、凋亡、癌症信号通路、NOTCH信号通路、MAPK信号通路（P<0.05）。结论 APOC1基因在PTC中高表达，与预后、免疫浸润相关，可以作为PTC诊断、预后、药物治疗的潜在靶点。

关键词:甲状腺乳头状癌;载脂蛋白C1;免疫浸润;生物信息学

Abstract:

Objective To investigate the expression level and clinical significance of Apolipoprotein C1 (APOC1) in papillary thyroid carcinoma (PTC) and paracarcinoma(PC) tissues. Methods UALCAN database and the HPA database were adopted to compare the differential expression of APOC1 mRNA in PTC and PC tissues, Kaplan-Meier Plotter database to predict the value APOC1 for PTC prognosis, and TIMER database to study the association of APOC1 with immune cells. The drug targets and cancer-related pathways of the top 5 key genes in PTC were analyzed using the GSCALite database. Finally, GSEA analysis was performed on the APOC1 gene. Results APOC1 mRNA expression level in PTC tissue was significantly higher than that in PC tissue, and the expression levels in PTC tissues of different clinical stages, patients’ age and gender, and lymph node metastasis were significantly higher than those in PC tissue respectively. APOC1 was associated with prognosis and immune infiltration of PTC.APOC1 was associated with multiple cancer pathways and could be suppressed by abiraterone, GSK-J4, and SR8278. And GSEA single-gene functional enrichment analysis revealed that APOC1 functions enriched in propionic acid metabolism, valine and isoleucine, tricarboxylic acid cycle, taurine metabolism, JAK-STAT signaling pathway, autoimmune thyroid disease, apoptosis, cancer signaling pathway, NOTCH signaling pathway, MAPK signaling pathway (P<0.05). Conclusion The APOC1 gene is highly expressed in PTC and associated with prognosis and immune infiltration of PTC, which indicates that APOC1 may be a potential target for PTC diagnosis, prognosis, and drug therapy.

Key words:Papillary thyroid carcinoma;APOC1;Immune infiltration;Bioinformatics analysis