甲状腺癌肿瘤干细胞相关基因分析
1. 昆明医科大学第一附属医院, 核医学科, 云南昆明 650032
2. 昆明医科大学药, 药学院暨省天然药物药理重点实验室, 云南昆明 650500
| 摘 要： | 目的：临床上不同类型甲状腺癌出现复发和耐药与肿瘤干细胞存在一定联系。通过探讨不同甲状腺癌细胞系的肿瘤干细胞相关基因转录水平的差异及与肿瘤通路的相关性以发现影响甲状腺癌进展的因素。方法：伤口愈合实验分析细胞迁移；比较不同甲状腺癌细胞系肿瘤干细胞相关基因CD133、OCT4、ABCG2、ALDH2、Nanog、CD44、CD24、EMT及甲状腺特异基因转录水平；利用R软件GSVA包结合TCGA数据库分析上述基因与肿瘤通路的相关性及基因间的相关性。结果：伤口愈合结果示甲状腺癌细胞系TPC-1和ATC的愈合能力较正常的细胞快。qPCR示与Nthy-ori 3-1相比，EGFR、CD44、CD24和ABCG2在ATC和TPC-1的表达具有显著性差异，EGFR和ABCG2在ATC高表达，而CD24基因却在TPC-1中高表达；TTF2在ATC和TPC-1均显著低表达。相关性分析示在甲状腺癌中ABCG2和OCT4与炎症反应、ALDH2与P53信号通路、CD24与ECM降解和P53信号通路、Nanog与MYC靶基因通路、CD44与活性氧（ROS）基因上调均呈显著负相关；EGFR与TGFB信号通路呈显著正相关。基因ALDH2、ABCG2、CD44与TPO和TG呈显著正相关。结论：不同类型甲状腺癌的肿瘤干细胞相关基因转录水平差异大且与肿瘤信号通路有显著的联系，可能与加剧甲状腺癌的进展有关。 |
| 关 键 词： | 甲状腺癌; 肿瘤干细胞相关基因; 转录水平; 相关性分析 |
| DOI： | 10.57237/j.mrf.2022.01.001 |
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收稿日期: 2022-08-31
接受日期: 2022-09-29
在线出版日期: 2022-11-01
Gene Analysis of Cancer Stem Cells in Thyroid Cancer
1. Department of Nuclear Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
2. School of Pharmacy and Provincial Key Laboratory of Natural Drug Pharmacology, Kunming Medical University, Kunming 650500, China
| Abstract: | Objective Recurrence and drug resistance in different thyroid cancer in the clinic are associated with tumor stem cells. To investigate the differences in transcript levels of tumor stem cell-associated genes in different thyroid cancer cell lines and their correlation with tumor pathways for identifing factors affecting thyroid cancer progression. Methods Wound healing assay was performed to analyze cell migration; to compare the transcript levels of tumor stem cell related genes CD133, OCT4, ABCG2, ALDH2, Nanog, CD44, CD24, EMT and thyroid specific genes in different thyroid cancer cell lines; to analyze the correlation between the above genes and tumor pathways and the correlation between genes using R software GSVA package combined with TCGA database. Results Wound healing results showed that thyroid cancer cell lines TPC-1 and ATC healed faster than normal cells. qPCR showed significantly different expression of EGFR, CD44, CD24 and ABCG2 in ATC and TPC-1 compared to Nthy-ori 3-1. EGFR and ABCG2 were highly expressed in ATC cell lines, while CD24 gene was highly expressed in TPC -1; TTF2 was significantly low expressed in both ATC and TPC-1 cell lines. Correlation analysis showed that ABCG2 and OCT4 were negatively correlated with inflammatory response, ALDH2 with P53 signaling pathway, CD24 with ECM degradation and P53 signaling pathway, Nanog with MYC target gene pathway, and CD44 with reactive oxygen species (ROS) gene upregulation in thyroid cancer; EGFR was positively correlated with TGFB signaling pathway. The genes ALDH2, ABCG2 and CD44 were significantly and positively correlated with TPO and TG. Conclusion The transcriptional levels of tumor stem cell genes differed greatly among different types of thyroid cancer and were significantly associated with tumor signaling pathways. It may be related to signaling pathways that exacerbate the development of thyroid cancer. |
| Keywords: | Thyroid Cancer; Tumor Stem Cell-Associated Gene; Transcript Level; Correlation Analysis |
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