Kim Dohun, Kim Yujin, Lee Bo Bin, Kim Dongho, Lee Ok-Jun, Jeong Pildu, Kim Wun-Jae, Cho Eun Yoon, Han Joungho, Shim Young Mog, Kim Duk-Hwan
Department of Thoracic and Cardiovascular Surgery, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju 28644, Korea.
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
J Clin Med. 2020 Sep 23;9(10):3067. doi: 10.3390/jcm9103067.
This study aimed to understand whether the effect of non-metastatic cells 1 (NME1) on recurrence-free survival (RFS) in early stage non-small cell lung cancer (NSCLC) can be modified by β-catenin overexpression and cisplatin-based adjuvant chemotherapy. Expression levels of NME1 and β-catenin were analyzed using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 425 early stage NSCLC patients. Reduced NME1 expression was found in 39% of samples. The median duration of follow-up was 56 months, and recurrence was found in 186 (44%) of 425 patients. The negative effect of reduced NME1 expression on RFS was worsened by cisplatin-based adjuvant chemotherapy (adjusted hazard ratio = 3.26, 95% CI = 1.16-9.17, = 0.03). β-catenin overexpression exacerbated the effect of reduced NME1 expression on RFS and the negative effect was greater when receiving cisplatin-based adjuvant chemotherapy: among patients treated with cisplatin-based adjuvant chemotherapy, hazard ratios of patients with reduced NME1 expression increased from 5.59 (95% confidence interval (CI) = 0.62-50.91, = 0.13) to 15.52 (95% CI = 2.94-82.38, = 0.001) by β-catenin overexpression, after adjusting for confounding factors. In conclusion, the present study suggests that cisplatin-based adjuvant chemotherapy needs to be carefully applied to early stage NSCLC patients with overexpressed β-catenin in combination with reduced NME1 expression.
本研究旨在了解非转移细胞1（NME1）对早期非小细胞肺癌（NSCLC）无复发生存期（RFS）的影响是否会因β-连环蛋白过表达和顺铂辅助化疗而改变。使用免疫组织化学方法分析了425例早期NSCLC患者福尔马林固定石蜡包埋组织中NME1和β-连环蛋白的表达水平。在39%的样本中发现NME1表达降低。中位随访时间为56个月，425例患者中有186例（44%）出现复发。基于顺铂的辅助化疗使NME1表达降低对RFS的负面影响恶化（调整后风险比=3.26，95%CI=1.16-9.17，P=0.03）。β-连环蛋白过表达加剧了NME1表达降低对RFS的影响，且在接受基于顺铂的辅助化疗时负面影响更大：在接受基于顺铂的辅助化疗的患者中，在调整混杂因素后，NME1表达降低的患者的风险比因β-连环蛋白过表达从5.59（95%置信区间（CI）=0.62-50.91，P=0.13）增加到15.52（95%CI=2.94-82.38，P=0.001）。总之，本研究表明，对于β-连环蛋白过表达且NME1表达降低的早期NSCLC患者，基于顺铂的辅助化疗需要谨慎应用。
