Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea.
J Thorac Oncol. 2012 Mar;7(3):528-34. doi: 10.1097/JTO.0b013e3182417830.
Hypoxia-inducible factor-1α (HIF-1α), which plays an essential role in the adaptive response of cells to hypoxia, is associated with aggressive tumor behavior. Furthermore, a relationship between excision repair cross-complementing 1 (ERCC1) expression and platinum resistance has been reported in patients with various malignancies. The aim of this study was to investigate the expression of HIF-1α and ERCC1 and to elucidate the clinical significance of their expression in patients with small cell lung cancer (SCLC) treated with front-line platinum-based chemotherapy.
SCLC biopsy samples were obtained before front-line platinum-based chemotherapy from 111 patients with SCLC (limited disease, 29; extensive disease [ED], 82) between January 2002 and December 2009 at Gyeongsang National University Hospital. The expression levels of HIF-1α and ERCC1 were assessed by immunohistochemistry.
High expression levels of ERCC1 and HIF-1α were observed in 49 (44.1%) and 71 (64.0%) of 111 patients, respectively. Expression of ERCC1 and HIF-1α was not significantly associated with age, sex, Eastern Cooperative Oncology Group performance status, weight loss, or response to treatment, regardless of stage. In ED-SCLC, low expression in the HIF-1α group showed statistically better survival compared with high expression in the HIF-1α group (p = 0.018). Multivariate analysis revealed that response to front-line platinum-based chemotherapy (p < 0.001), good Eastern Cooperative Oncology Group performance status (0-1) (p = 0.002), and low expression of HIF-1α (p = 0.004) were independent predictors of better overall survival in ED-SCLC.
Low expression of HIF-1α may be a useful predictor of better overall survival in ED-SCLC patients treated with front-line platinum-based chemotherapy.
缺氧诱导因子-1α（HIF-1α）在细胞对缺氧的适应反应中发挥着重要作用，与侵袭性肿瘤行为有关。此外，在各种恶性肿瘤患者中，已经报道了切除修复交叉互补基因 1（ERCC1）表达与铂类耐药之间的关系。本研究旨在探讨 HIF-1α和 ERCC1 的表达，并阐明其在接受一线铂类化疗的小细胞肺癌（SCLC）患者中的表达的临床意义。
本研究纳入了 2002 年 1 月至 2009 年 12 月在韩国国立庆尚大学医院接受一线铂类化疗的 111 例 SCLC 患者（局限期 29 例，广泛期 82 例）的 SCLC 活检样本。采用免疫组织化学法检测 HIF-1α和 ERCC1 的表达水平。
111 例患者中，分别有 49 例（44.1%）和 71 例（64.0%）患者的 ERCC1 和 HIF-1α表达水平较高。无论分期如何，ERCC1 和 HIF-1α的表达与患者的年龄、性别、东部肿瘤协作组（ECOG）体能状态、体重减轻或治疗反应均无显著相关性。在广泛期 SCLC 中，HIF-1α低表达组的生存情况明显优于 HIF-1α高表达组（p=0.018）。多因素分析显示，一线铂类化疗的反应（p<0.001）、良好的 ECOG 体能状态（0-1）（p=0.002）和 HIF-1α的低表达（p=0.004）是广泛期 SCLC 患者总生存期的独立预后因素。
HIF-1α的低表达可能是接受一线铂类化疗的广泛期 SCLC 患者总生存期更好的有用预测指标。
