Prognostic Significance of the Metabolic Marker Hexokinase-2 in Various Solid Tumors: A Meta-Analysis

ObjectiveRecently, numerous studies have reported that hexokinase-2 (HK2) is aberrantly expressed in cancer, indicating that HK2 plays a pivotal role in the development and progression of cancer. However, its prognostic significance in solid tumor remains unclear. Accordingly, we performed a meta-analysis to assess the prognostic value of HK2 in solid tumor.MethodsEligible studies were identified using PubMed, Embase, and Web of Science databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) or progression-free survival (PFS)/disease-free survival (DFS)/relapse-free survival (RFS) were estimated with random effects or fixed effects models, respectively. Subgroup analysis was also performed according to patients’ ethnicities, tumor types, detection methods, and analysis types.ResultsData from 21 included studies with 2532 patients were summarized. HK2 overexpression was significantly associated with worse OS (pooled HR = 1.90, 95% CI = 1.51–2.38, p p p p = 0.020), colorectal cancer (pooled HR = 2.89, 95% CI = 1.62–5.16, p p = 0.864). No publication bias was found in the included studies for OS (Begg’s test, p = 0.325; Egger’s test, p = 0.441).ConclusionIn this meta-analysis, we identified that elevated HK2 expression was significantly associated with shorter OS and PFS in patients with solid tumor, but the association varies according to cancer type.

【研究目的】近期多项研究报道，己糖激酶2（hexokinase-2, HK2）在癌症中存在异常表达，提示其在癌症的发生与进展中发挥关键作用。然而，HK2在实体瘤中的预后意义仍不明确。为此，本研究开展荟萃分析以评估HK2在实体瘤中的预后价值。
【研究方法】通过PubMed、Embase及Web of Science数据库检索符合纳入标准的研究。分别采用随机效应模型或固定效应模型，估算总生存期（overall survival, OS）、无进展生存期（progression-free survival, PFS）/无病生存期（disease-free survival, DFS）/无复发生存期（relapse-free survival, RFS）的合并风险比（hazard ratios, HRs）及95%置信区间（confidence intervals, CIs）。此外，根据患者种族、肿瘤类型、检测方法及分析类型进行亚组分析。
【研究结果】共纳入21项研究，涉及2532例患者。HK2过表达与较差的总生存期显著相关（合并HR=1.90，95%CI=1.51~2.38，P<0.001）；HK2过表达与结直肠癌患者的不良预后显著相关（合并HR=2.89，95%CI=1.62~5.16，P<0.001），而在其他肿瘤类型中未观察到明显统计学差异（P=0.864）。针对总生存期的纳入研究未发现明显发表偏倚（Begg检验：P=0.325；Egger检验：P=0.441）。
【研究结论】本项荟萃分析结果显示，实体瘤患者中HK2高表达与更短的总生存期及无进展生存期显著相关，但该关联因癌症类型不同而存在差异。