Department of Head and Neck Tumor Surgery, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning, Guangxi Zhuang Autonomous Region, PR China.
Department of Radiotherapy, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning, Guangxi Zhuang Autonomous Region, PR China.
Comput Biol Chem. 2020 Jun;86:107258. doi: 10.1016/j.compbiolchem.2020.107258. Epub 2020 Apr 9.
Thyroid carcinoma (THCA) is one of the most frequent endocrine cancers and has increasing morbidity. Annexin A2 (ANXA2) has been found to be highly expressed in various cancers; however, its expression level and potential mechanism in THCA remain unknown. This study investigated the clinicopathological value and primary molecular machinery of ANXA2 in THCA.
Public RNA-sequencing and microarray data were obtained and analyzed with ANXA2 expression in THCA and corresponding non-cancerous thyroid tissue. A Pearson correlation coefficient calculation was used for the acquisition of ANXA2 coexpressed genes, while edgR, limma, and Robust Rank Aggregation were employed for differentially expressed gene (DEG) in THCA. The probable mechanism of ANXA2 in THCA was predicted by gene ontology and pathway enrichment. A dual-luciferase reporter assay was employed to confirm the targeting relationships between ANXA2 and its predicted microRNA (miRNA).
Expression of ANXA2 was significantly upregulated in THCA tissues with a summarized standardized mean difference of 1.09 (P < 0.0001) based on 992 THCA cases and 589 cases of normal thyroid tissue. Expression of ANXA2 was related to pathologic stage. Subsequently, 1442 genes were obtained when overlapping 4542 ANXA2 coexpressed genes with 2248 DEGs in THCA; these genes were mostly enriched in pathways of extracellular matrix-receptor interaction, cell adhesion molecules, and complement and coagulation cascades. MiR-23b-3p was confirmed to target ANXA2 by dual-luciferase reporter assay.
Upregulated expression of ANXA2 may promote the malignant biological behavior of THCA by affecting the involving pathways or being targeted by miR-23b-3p.
甲状腺癌（THCA）是最常见的内分泌癌之一，发病率不断上升。膜联蛋白 A2（ANXA2）在各种癌症中表达水平较高，但在 THCA 中的表达水平及其潜在机制尚不清楚。本研究探讨了 ANXA2 在 THCA 中的临床病理价值和主要分子机制。
获取并分析了公共 RNA 测序和微阵列数据，以获取 THCA 及相应非癌性甲状腺组织中 ANXA2 的表达情况。采用 Pearson 相关系数计算获取 ANXA2 共表达基因，采用 edgR、limma 和 Robust Rank Aggregation 分析 THCA 中的差异表达基因（DEG）。通过基因本体和途径富集预测 ANXA2 在 THCA 中的可能机制。采用双荧光素酶报告实验验证 ANXA2 与其预测的微小 RNA（miRNA）之间的靶向关系。
基于 992 例 THCA 病例和 589 例正常甲状腺组织，ANXA2 在 THCA 组织中的表达明显上调，汇总标准化均数差为 1.09（P<0.0001）。ANXA2 的表达与病理分期有关。随后，在与 THCA 中 2248 个 DEG 重叠的 4542 个 ANXA2 共表达基因中获得了 1442 个基因；这些基因主要富集在细胞外基质-受体相互作用、细胞黏附分子和补体及凝血级联途径中。双荧光素酶报告实验证实 miR-23b-3p 可靶向 ANXA2。
ANXA2 的上调表达可能通过影响涉及的途径或被 miR-23b-3p 靶向作用来促进 THCA 的恶性生物学行为。
