Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Oncology. 2018;95(1):20-30. doi: 10.1159/000488201. Epub 2018 Apr 25.
Multimodal treatments that include preoperative platinum-based chemotherapy are fundamental to the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the predictive value of DNA repair protein expression in surgically resected NSCLCs in terms of prognosis and responses to platinum-containing chemotherapy.
This retrospective study included 136 patients with NSCLC who were treated with preoperative platinum-based chemotherapy, followed by curative lung resection. ATM, RAD51, LKB1, H2AX, and SIRT1 expression levels were analyzed in resected tumor specimens via immunostaining and were used to classify patients and compare survival and responses to chemotherapy.
SIRT1 expression correlated significantly with improved responses to platinum-based chemotherapy (odds ratio, 2.28; p = 0.024), progression-free survival (hazard ratio [HR], 0.74; p = 0.036), overall survival (HR, 0.63; p = 0.006), and tumor-bearing survival (HR, 0.62; p = 0.014). After adjusting for clinical variables, the HR of SIRT1 expression remained significant for overall survival (HR, 0.59; p = 0.039) but not for progression-free survival (HR, 0.74; p = 0.183). No prognostic stratification was observed for the other 4 markers.
Patients with SIRT1-expressing NSCLC had superior responses to chemotherapy and longer survival durations than those with SIRT1-negative cancer.
包含术前铂类化疗的多模态治疗是治疗晚期非小细胞肺癌(NSCLC)的基础。本研究旨在探讨 DNA 修复蛋白在接受术前铂类化疗的可切除 NSCLC 中的表达对预后和对含铂化疗反应的预测价值。
本回顾性研究纳入了 136 例接受术前铂类化疗、随后行根治性肺切除术的 NSCLC 患者。通过免疫组化分析切除肿瘤标本中的 ATM、RAD51、LKB1、H2AX 和 SIRT1 表达水平,并用于对患者进行分类,比较生存和对化疗的反应。
SIRT1 表达与对铂类化疗的反应改善显著相关(比值比,2.28;p = 0.024)、无进展生存期(风险比[HR],0.74;p = 0.036)、总生存期(HR,0.63;p = 0.006)和肿瘤携带生存期(HR,0.62;p = 0.014)。在校正临床变量后,SIRT1 表达对总生存期的 HR 仍然显著(HR,0.59;p = 0.039),但对无进展生存期的 HR 不显著(HR,0.74;p = 0.183)。其他 4 个标志物未观察到预后分层。
与 SIRT1 阴性癌症患者相比,SIRT1 表达阳性的 NSCLC 患者对化疗的反应更好,生存时间更长。