Expression of ANGPTL2 and its impact on papillary thyroid cancer
Expression of ANGPTL2 and its impact on papillary thyroid cancer
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ANGPTL2的表达及其对甲状腺乳头状癌的影响
DOI：
10.1186/s12935-019-0908-9
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发表时间：
2019-07-30
影响因子：
5.8
通讯作者：
Zhao, Dong
中科院分区：
文献类型：
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作者：
Yang, Longyan;Sun, Rongxin;Zhao, Dong
研究背景虽然大多数甲状腺癌患者预后良好，但仍有约20%的甲状腺乳头状癌（papillary thyroid carcinoma，PTC）患者经常规治疗后仍有较高的转移和复发率，导致PTC患者的高死亡率。肿瘤增殖、转移和侵袭是PTC侵袭性的重要预测因子，也是癌症相关死亡的关键因素。血管生成素样蛋白2（Angiopoietin-like 2，ANGPTL 2）是血管生成素（angiopoietin，ANGPTL）家族的一种分泌蛋白，参与多种肿瘤细胞增殖和转移的调控。然而，ANGPTL 2是否在PTC的进展中起作用，特别是在PTC的转移和复发中，仍不清楚。因此，本研究的目的是评估ANGPTL 2在PTC和正常甲状腺以及癌旁组织中的水平。此外，ANGPTL 2对PTC细胞增殖，转移，复发和侵袭的影响进行了评估，以探讨ANGPTL 2是否可能成为PTC治疗和癌症预后的新靶点的可能性。通过细胞计数试剂盒-8（CCK 8）测定、细胞划痕试验和transwell测定研究ANGPTL 2对甲状腺癌细胞增殖和转移的生物学作用。用TCGA数据集评估ANGPTL 2表达水平与甲状腺癌增殖、迁移和转移的相关性，并通过基因集富集分析进行分析。接受者操作特征分析用于评估ANGPTL 2作为预测甲状腺癌的生物标志物的效用。结果ANGPTL 2在甲状腺癌中的表达高于癌旁正常甲状腺组织，ANGPTL 2表达随甲状腺癌进展而增加，ANGPTL 2促进甲状腺癌细胞增殖，ANGPTL 2促进甲状腺癌细胞凋亡，ANGPTL 2促进甲状腺癌细胞增殖，ANGPTL 2促进甲状腺癌细胞凋亡，ANGPTL 2促进甲状腺癌细胞增殖，ANGPTL 2促进甲状腺癌细胞凋亡。（4）ANGPTL 2促进甲状腺癌细胞的迁移和侵袭;（5）ANGPTL 2在甲状腺癌患者中的高水平表达与不良预后显著相关。结论ANGPTL 2可促进甲状腺癌细胞的增殖、转移和侵袭。ANGPTL 2可能被认为是甲状腺癌患者诊断和预后的潜在生物标志物。ANGPTL 2作为甲状腺乳头状癌预后指标和治疗靶点的可能性有待进一步研究。
BackgroundAlthough the most thyroid carcinoma patients have good prognosis, around 20% of papillary thyroid carcinoma (PTC) patients have a high rate of metastasis and recurrence after routine treatment, which causes high lethality with these patients. Tumor proliferation, metastasis, and invasion are important predictors of PTC invasiveness and are key factors in cancer-related death. Angiopoietin-like 2 (ANGPTL2), a secreted protein which belongs to the angiopoietin (ANGPTL) family, was reported to be involved in the regulation of several different type of cancer cell proliferation and metastasis. However, whether ANGPTL2 plays a role in the progression of PTC, particularly in metastasis and recurrence of PTC, remains unclear. Hence, the purpose of this study was to evaluate the level of ANGPTL2 in PTC and normal thyroid, as well as para-cancerous tissue. Furthermore, the impact of ANGPTL2 on PTC cell proliferation, metastasis, recurrence and invasion was assessed to investigate the possibility whether ANGPTL2 may become a novel target for PTC therapy and cancer prognosis.Materials and methodsThe level of ANGPTL2 in PTC and para-cancerous tissue was assessed by immunohistochemistry. The biological effect of ANGPTL2 on thyroid cancer cell proliferation and metastasis was investigated by the Cell Counting Kit-8 (CCK8) assay, cell scratch test, and transwell assay. Correlations of ANGPTL2 expression levels with proliferation, migration, and metastasis of thyroid cancer were assessed with the TCGA data set and analyzed by gene set enrichment analysis. Receiver operating characteristic analysis was used to evaluate the utility of ANGPTL2 as a biomarker for prediction of thyroid cancer. Survival analysis was performed using the thyroid cancer database in K–M Plotter to detect correlations between survival time and ANGPTL2 levels.ResultsCurrent study revealed that: (1) ANGPTL2 was highly expressed in thyroid cancer in comparison with adjacent normal thyroid tissue; (2) ANGPTL2 expression was increased with thyroid tumor progression; (3) ANGPTL2 increased proliferation of thyroid cancer cells; (4) ANGPTL2 promoted migration and invasion of thyroid cancer cells; (5) high level of ANGPTL2 in thyroid cancer patients were significantly associated with a poor prognosis. The patients showed a higher metastasis and recurrence rate.ConclusionANGPTL2 promoted and enhanced proliferation, metastasis, and invasion of thyroid cancer cells. ANGPTL2 may be considered as a potential biomarker for diagnosis and prognosis of thyroid cancer patients. Further evaluation needs to be done to analyze the possibility of taking ANGPTL2 as a prognostic marker and therapeutic target for papillary thyroid cancer.