First Department of Colorectal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
ICU of Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
Int J Mol Med. 2018 Apr;41(4):2185-2192. doi: 10.3892/ijmm.2018.3432. Epub 2018 Jan 29.
Annexin A9 (ANXA9), a member of annexin family, has been reported be associated with colorectal cancer (CRC) carcinogenesis. However, the clinical significance of ANXA9 in CRC, particularly its correlation to invasion and metastasis remains ambiguous. The aim of the present study was to investigate the significance of ANXA9 in CRC and understand the molecular mechanism of ANXA9 in CRC invasion and metastasis. Expression levels of the ANXA9 protein in CRC tissues were detected using immunohistochemistry (IHC), and the clinical and prognostic value of ANXA9 was investigated. ANXA9‑siRNA was utilized to investigate the effect and molecular mechanism of ANXA9 in HCT116 cells. The IHC result demonstrated that the positivity rate of the ANXA9 protein in CRC tissue was significantly higher than that in adjacent mucosa (P<0.05), which was consistent with the western blot results. ANXA9 protein expression levels are associated with invasion depth and lymphatic metastasis. Furthermore, patients with ANXA9‑positive expression demonstrated a poor prognosis and ANXA9 was an independent risk factor for survival (P<0.05). After inhibiting ANXA9 in HCT116 cells, the activity and metastatic and invasion capacity of cells decreased significantly, and expression levels of ADAM metallopeptidase domain 17 and matrix metallopeptidase 9 were significantly downregulated, while the expression levels of tissue inhibitors of metalloproteinases‑1 and E‑cadherin were upregulated (P<0.05). Thus, positive ANXA9 expression may present as a novel marker for predicting poor prognosis in CRC patients, and ANXA9 may promote the invasion and metastasis of CRC by regulating invasion and metastasis‑associated genes.
膜联蛋白 A9(ANXA9),作为膜联蛋白家族的一员,已被报道与结直肠癌(CRC)的发生有关。然而,ANXA9 在 CRC 中的临床意义,特别是与侵袭和转移的相关性仍然不明确。本研究旨在探讨 ANXA9 在 CRC 中的意义,并了解 ANXA9 在 CRC 侵袭和转移中的分子机制。通过免疫组织化学(IHC)检测 CRC 组织中 ANXA9 蛋白的表达水平,研究 ANXA9 的临床和预后价值。利用 ANXA9-siRNA 研究 ANXA9 在 HCT116 细胞中的作用及其分子机制。IHC 结果表明,CRC 组织中 ANXA9 蛋白的阳性率明显高于相邻黏膜(P<0.05),与 Western blot 结果一致。ANXA9 蛋白表达水平与浸润深度和淋巴转移有关。此外,ANXA9 阳性表达的患者预后较差,ANXA9 是生存的独立危险因素(P<0.05)。在 HCT116 细胞中抑制 ANXA9 后,细胞的活性和转移及侵袭能力明显下降,ADAM 金属肽酶结构域 17 和基质金属蛋白酶 9 的表达水平明显下调,而组织金属蛋白酶抑制剂 1 和 E-钙黏蛋白的表达水平上调(P<0.05)。因此,ANXA9 阳性表达可能成为预测 CRC 患者预后不良的新标志物,ANXA9 可能通过调节侵袭和转移相关基因促进 CRC 的侵袭和转移。