Association Between Hypoxia-Inducible Factor-2α (HIF-2α) Expression and Colorectal Cancer and Its Prognostic Role: a Systematic Analysis
Association Between Hypoxia-Inducible Factor-2α (HIF-2α) Expression and Colorectal Cancer and Its Prognostic Role: a Systematic Analysis
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缺氧诱导因子-2α (HIF-2α) 表达与结直肠癌的关联及其预后作用：系统分析
DOI：
10.1159/000491806
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Hou, Fenggang
中科院分区：
文献类型：
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作者：
Han, Susu;Huang, Tao;Hou, Fenggang
背景/目的：尽管一些研究表明HIF-2α的表达与结直肠癌(CRC)的不良预后相关，但在结直肠癌中的预后结果仍然相互矛盾。本研究旨在评估HIF-2α表达与结直肠癌临床病理特征的关系，并探讨HIF-2α表达对结直肠癌预后的潜在作用。方法：从现有出版物、癌症基因组图谱(TCGA)和基因表达总览(GEO)数据库中计算合并优势比(OR)或风险比(HR)。使用试验序贯分析(TSA)估计所需样本信息。结果：HIF-2α蛋白在结直肠癌中的表达高于正常结肠组织(OR=150.49，P<；0.001)，男性高于女性(OR=1.47，P=0.008)，高级别低于低级别(OR=0.49，P=0.029)。TSA验证了上述结果的可靠性。在总生存期(OS)、疾病特异性生存期(DSS)、无转移生存期和无复发生存期中，HIF-2α的表达与结直肠癌的预后无关，HIF-2α的表达变化与结直肠癌的OS或无病生存期(DFS)无明显相关性。HIF-2α和血管内皮生长因子(VEGFA、VEGFB或VEGFFC)的表达与结直肠癌的无转移生存率相关(HR分别为6.95、113.51和8.11)。未发现HIF-2α的表达与其他肿瘤的DFS相关，但HIF-2α的表达与结直肠癌的DFS相关(HR=1.23，P=0.037)。此外，在某些癌症(B细胞淋巴瘤和肺腺癌：OS，多发性骨髓瘤：DSS，乳腺癌：无远处转移生存期，脂肪肉瘤：无远处复发生存期)中，HIF-2α的表达与良好的生存益处有关(均为HRs<；1，P<；0.05)。结论：HIF-2α的表达可能与结直肠癌的发生有关，男性高于女性，与肿瘤分化程度呈负相关，与结直肠癌的预后相关。还需要更多的前瞻性研究。(C)2018年作者(S)由S.Karger AG，巴塞尔出版
Background/Aims: Although some studies showed that HIF-2 alpha expression was correlated with an unfavorable prognosis in colorectal cancer (CRC), the prognostic results remain conflicting in CRC. The present study was performed to evaluate the association between HIF-2 alpha expression and the clinicopathological features of this disease and to examine the potential prognostic role of HIF-2 alpha expression in CRC. Methods: Pooled odds ratios (ORs) or hazard ratios (HRs) were calculated from available publications, The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. Trial sequential analysis (TSA) was used to estimate the required sample information. Results: HIF-2 alpha protein expression was more frequent in CRC than in normal colonic tissues (OR = 150.49, P < 0.001), higher in male than female CRC patients (OR = 1.47, P = 0.008), and lower in high-grade than low-grade CRC (OR = 0.49, P = 0.029). TSA verified the reliability of the above results. HIF-2 alpha expression was not linked to the prognosis of CRC in overall survival (OS), disease-specific survival (DSS), metastasis-free survival, and relapse-free survival, and no significant correlation was found between HIF-2 alpha alteration and OS or disease-free survival (DFS) of CRC. Expression of both HIF-2 alpha and vascular endothelial growth factor (VEGFA, VEGFB, or VEGFC) was associated with a poor metastasis-free survival of CRC (HR = 6.95, HR = 113.51, and HR = 8.11, respectively). No association was observed between HIF-2 alpha expression and DFS in other cancers, but HIF-2 alpha expression was correlated with a worse DFS of CRC (HR = 1.23, P = 0.037). Moreover, HIF-2 alpha expression was linked to a good survival benefit in some cancers (B-cell lymphoma and lung adenocarcinoma: OS, multiple myeloma: DSS, breast cancer: distant metastasis-free survival, liposarcoma: distant recurrence-free survival) (all HRs < 1, Ps < 0.05). Conclusions: HIF-2 alpha expression may be associated with the carcinogenesis of CRC, which is higher in males than in females, negatively linked to tumor differentiation, and correlated with a worse DFS of CRC. Additional prospective studies are needed. (C) 2018 The Author(s) Published by S. Karger AG, Basel