Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Department of General Surgery, People's Hospital of Tibet Autonomous Region, Tibet 850000, China.
Dis Markers. 2022 Dec 2;2022:2283541. doi: 10.1155/2022/2283541. eCollection 2022.
Hepatoblastoma (HB) is the most common malignant liver tumor in children. High-risk patients, especially those with tumor metastasis, have poor prognosis. Serpin family E member 2 (SERPINE2) is overexpressed in a variety of tumors, especially adenocarcinoma, and promotes tumor invasion and metastasis. The function and mechanism of SERPINE2 in HB are still unclear. The purpose of this study was to investigate the potential clinical prognostic value and molecular mechanism of SERPINE2 in HB.
We performed bioinformatics analyses on HB microarray data GSE131329 to study the role of SERPINE2. The expression level of SERPINE2 in HB and its clinical significance were further analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry. After constructing the SERPINE2 overexpression and knockdown in HepG2 and HUH6 cells, the 5-ethynyl-29-deoxyuridine (EdU) assay, wound healing assay, Transwell experiment, and apoptosis assay were performed to explore the role of SERPINE2 in HB progress.
Upregulation of SERPINE2 was found in HB tissues and was associated with a poor prognosis. Moreover, the SERPINE2 expression was related to tumor size, vascular invasion, and tumor metastasis. The Cox regressions show that high SERPINE2 expression is an independent risk factor for HB. SERPINE2 overexpression remarkably enhanced HB cell migration and invasion and suppressed apoptosis, while knockdown of SERPINE2 exerted the opposite effect. In addition, SERPINE2 facilitated the epithelial to mesenchymal transformation (EMT) phenotype of HB cells in vitro.
Our findings indicated that SERPINE2 accelerates HB progression, suggesting that SERPINE2 may be a potential prognostic biomarker and an underlying therapeutic target for HB.
肝母细胞瘤（HB）是儿童最常见的恶性肝肿瘤。高危患者，尤其是有肿瘤转移的患者，预后较差。丝氨酸蛋白酶抑制剂家族 E 成员 2（SERPINE2）在多种肿瘤中过度表达，特别是腺癌，并促进肿瘤侵袭和转移。SERPINE2 在 HB 中的功能和机制尚不清楚。本研究旨在探讨 SERPINE2 在 HB 中的潜在临床预后价值和分子机制。
我们对 HB 微阵列数据 GSE131329 进行了生物信息学分析，以研究 SERPINE2 的作用。通过定量实时聚合酶链反应（qRT-PCR）、Western blot 和免疫组织化学进一步分析 SERPINE2 在 HB 中的表达水平及其临床意义。在构建 HepG2 和 HUH6 细胞中 SERPINE2 的过表达和敲低后，进行 5-乙炔基-2'-脱氧尿苷（EdU）检测、划痕愈合试验、Transwell 实验和凋亡检测，以探讨 SERPINE2 在 HB 进展中的作用。
发现 SERPINE2 在 HB 组织中上调，与预后不良相关。此外，SERPINE2 的表达与肿瘤大小、血管侵犯和肿瘤转移有关。Cox 回归显示，高 SERPINE2 表达是 HB 的独立危险因素。SERPINE2 的过表达显著增强了 HB 细胞的迁移和侵袭能力，并抑制了凋亡，而 SERPINE2 的敲低则产生了相反的效果。此外，SERPINE2 促进了 HB 细胞体外的上皮间质转化（EMT）表型。
我们的研究结果表明，SERPINE2 加速了 HB 的进展，提示 SERPINE2 可能是 HB 的一个潜在预后标志物和治疗靶点。
