Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC 20057, USA; Institute for Innovative Cancer Research, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, 463-712, Republic of Korea.
Lung Cancer. 2018 Feb;116:38-45. doi: 10.1016/j.lungcan.2017.12.010. Epub 2017 Dec 15.
Cripto-1 (CR-1) plays a critical role in the activation of SMAD, SRC, and epithelial-to-mesenchymal transition (EMT) pathways and has been shown to be prognostic in several cancer types. In addition, we showed that CR-1 renders EGFR-mutated NSCLC cells resistant to EGFR-TKI through the activation of SRC and EMT via miR-205 downregulation. This study aimed to investigate the correlation between expression of CR-1 and miR-205 and prognosis of NSCLC patients with or without EGFR mutations.
A total of 265 patients with stage I (AJCC 6th edition) radically resected NSCLC were tested for CR-1 expression and EGFR mutations by immunohistochemistry and miR-205 expression via qPCR assay.
CR-1 expression was evaluated with immunohistochemistry using a tissue microarray on 265 T1-2N0 surgical NSCLC samples. Of the 265 tumors, 250 (94%) expressed various levels of CR-1. A significant inverse correlation was identified between expression of miR-205 and CR-1. NSCLC patients (T1N0, n = 106) with high CR-1 expression had worse prognosis (shorter recurrence-free survival, p = .045) than those with low CR-1 expression. A similar trend was observed in NSCLC patients with normal preoperative carcinoembryonic antigen (CEA) levels (serum CEA levels <5 ng/ml; n = 179; p = .085); however, no significant correlation was found between CR-1 expression and survival rate in the T2N0 or high CEA groups. In addition, NSCLC patients with low miR-205 expression (n = 126) had poorer prognosis in terms of recurrence than those with high miR-205 expression (n = 127; p = .001).
High CR-1 expression is correlated with poor prognosis in NSCLC with low tumor burden and may be used to select high-risk patients for adjuvant chemotherapy in early NSCLC. Moreover, low miR-205 expression likely related to high CR-1 expression could be a prognostic marker for patients with NSCLC.
CR-1（Crypto-1）在 SMAD、SRC 和上皮间质转化（EMT）通路的激活中起着关键作用，并且在几种癌症类型中被证明具有预后意义。此外，我们发现 CR-1 通过下调 miR-205 来激活 SRC 和 EMT，从而使 EGFR 突变的 NSCLC 细胞对 EGFR-TKI 产生耐药性。本研究旨在探讨 CR-1 和 miR-205 的表达与 NSCLC 患者有无 EGFR 突变的相关性。
通过免疫组化检测 265 例 I 期（AJCC 第 6 版）根治性切除 NSCLC 患者的 CR-1 表达和 EGFR 突变，并通过 qPCR 检测 miR-205 的表达。
使用组织微阵列对 265 例 T1-2N0 手术 NSCLC 样本进行免疫组化检测 CR-1 表达。在 265 例肿瘤中，250 例（94%）表达了不同水平的 CR-1。miR-205 表达与 CR-1 表达呈显著负相关。高 CR-1 表达的 NSCLC 患者（T1N0，n=106）无复发生存期较短（p=0.045），预后较差，而低 CR-1 表达的患者预后较好。在术前癌胚抗原（CEA）水平正常（血清 CEA 水平<5ng/ml；n=179；p=0.085）的 NSCLC 患者中也观察到类似的趋势；然而，在 T2N0 或高 CEA 组中，CR-1 表达与生存率之间无显著相关性。此外，miR-205 低表达（n=126）的 NSCLC 患者复发率较差，而 miR-205 高表达（n=127）的患者预后较好（p=0.001）。
在低肿瘤负荷的 NSCLC 中，高 CR-1 表达与不良预后相关，可能用于选择早期 NSCLC 辅助化疗的高危患者。此外，与高 CR-1 表达相关的低 miR-205 表达可能是 NSCLC 患者的预后标志物。
