Chen Zhigang, He Xin, Xia Wenjie, Huang Qi, Zhang Zhigang, Ye Jun, Ni Chao, Wu Pin, Wu Dang, Xu Jinghong, Qiu Fuming, Huang Jian
Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China ; Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences), Zhejiang University School of Medicine, Hangzhou, China.
PLoS One. 2013 Dec 6;8(12):e80337. doi: 10.1371/journal.pone.0080337. eCollection 2013.
The prognostic value of HIFs in colorectal cancer was evaluated in a large number of studies, but the conclusions were inconclusive. Meanwhile, clinicopathologic differences of HIF-1α and HIF-2α were rarely compared in recent studies.
Identical search strategies were used to search relevant literatures in the PubMed and Web of Science databases. The prognostic significances and clinicopathological differences of HIFs in CRC were analyzed.
A total of 23 studies comprising 2984 CRC patients met the inclusion criteria. The results indicated that overexpressed HIFs were significantly associated with increase of mortality risk, including overall survival (OS) (HR 2.06 95%CI 1.55-2.74) and disease free survival (HR 2.84, 95%CI 1.87-4.31). Subgroup analysis revealed that both overexpressed HIF-1α and HIF-2α had correlations with worse prognosis. The pooled HRs were 2.01 (95% CI: 1.55-2.6) and 2.07(95% CI: 1.01-4.26). Further subgroup analysis on HIF-1α was performed by study location, number of patients, quality score and cut-off value. The results showed that HIF-1α overexpression was significantly associated with poor OS, particularly in Asian countries (HR 2.3, 95% CI: 1.74-3.01), while not in European or other countries. In addition, overexpression of HIF-1α was closely related with these clinicopathological features, including Dukes' stages (OR 0.39, 95% CI: 0.17-0.89), UICC stages (OR 0.42 95% CI: 0.3-0.59), depth of invasion (OR 0.71, 95% CI: 0.51-0.99), lymphnode status (OR 0.49, 95% CI: 0.32-0.73) and metastasis (OR 0.29, 95% CI: 0.11-0.81). While overexpression of HIF-2α was only associated with grade of differentiation (OR 0.48, 95% CI: 0.29-0.81).
This study showed that both HIF-1α and HIF-2α overexpression were associated with an unfavorable prognosis. HIF-1α overexpression seemed to be associated with worse prognosis in Asian countries. Additionally, HIF-1α and HIF-2α indicated distinct clinicopathologic features.
大量研究评估了低氧诱导因子（HIFs）在结直肠癌中的预后价值，但结论尚无定论。同时，近期研究很少比较HIF-1α和HIF-2α的临床病理差异。
采用相同的检索策略在PubMed和Web of Science数据库中检索相关文献。分析HIFs在结直肠癌中的预后意义和临床病理差异。
共有23项研究、2984例结直肠癌患者符合纳入标准。结果表明，HIFs过表达与死亡风险增加显著相关，包括总生存期（OS）（风险比[HR] 2.06，95%置信区间[CI] 1.55 - 2.74）和无病生存期（HR 2.84，95%CI 1.87 - 4.31）。亚组分析显示，HIF-1α和HIF-2α过表达均与较差的预后相关。合并后的HR分别为2.01（95%CI：1.55 - 2.6）和2.07（95%CI：1.01 - 4.26）。通过研究地点、患者数量、质量评分和临界值对HIF-1α进行进一步亚组分析。结果显示，HIF-1α过表达与较差的总生存期显著相关，尤其是在亚洲国家（HR 2.3，95%CI：1.74 - 3.01），而在欧洲或其他国家则不然。此外，HIF-1α过表达与这些临床病理特征密切相关，包括Dukes分期（比值比[OR] 0.39，95%CI：0.17 - 0.89）、国际抗癌联盟（UICC）分期（OR 0.42，95%CI：0.3 - 0.59）、浸润深度（OR 0.71，95%CI：0.51 - 0.99）、淋巴结状态（OR 0.49，95%CI：0.32 - 0.73）和转移（OR 0.29，95%CI：0.11 - 0.81）。而HIF-2α过表达仅与分化程度相关（OR 0.48，95%CI：0.29 - 0.81）。
本研究表明，HIF-1α和HIF-2α过表达均与不良预后相关。HIF-1α过表达在亚洲国家似乎与更差的预后相关。此外，HIF-1α和HIF-2α表现出不同的临床病理特征。
