Department of Pneumology, Institut Clínic Respiratori (ICR), Hospital Clínic de Barcelona, University of Barcelona, IDIBAPS, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Casanova 143, 08036, Barcelona, Spain.
BMC Pulm Med. 2017 Dec 13;17(1):197. doi: 10.1186/s12890-017-0542-z.
NKX2-1, a key molecule in lung development, is highly expressed in non-small cell lung cancer (NSCLC), particularly in lung adenocarcinoma (ADK), where it is a diagnostic marker. Studies of the prognostic role of NKX2-1 in NSCLC have reported contradictory findings. Two microRNAs (miRNAs) have been associated with NKX2-1: miR-365, which targets NKX2-1; and miR-33a, which is downstream of NKX2-1. We have examined the effect of NKX2-1, miR-365 and miR-33a on survival in a cohort of early-stage NSCLC patients and in sub-groups of patients classified according to the mutational status of TP53, KRAS, and EGFR.
mRNA and miRNA expression was determined using TaqMan assays in 110 early-stage NSCLC patients. TP53, KRAS, and EGFR mutations were assessed by Sanger sequencing.
NKX2-1 expression was upregulated in never-smokers (P = 0.017), ADK (P < 0.0001) and patients with wild-type TP53 (P = 0.001). A negative correlation between NKX2-1 and miR-365 expression was found (ρ = -0.287; P = 0.003) but there was no correlation between NKX2-1 and miR-33a expression. Overall survival (OS) was longer in patients with high expression of NKX2-1 than in those with low expression (80.8 vs 61.2 months (P = 0.035), while a trend towards longer OS was observed in patients with low miR-365 levels (P = 0.07). The impact of NKX2-1 on OS and DFS was higher in patients with neither TP53 nor KRAS mutations. Higher expression of NKX2-1 was related to higher OS (77.6 vs 54 months; P = 0.017) and DFS (74.6 vs 57.7 months; P = 0.006) compared to low expression. The association between NKX2-1 and OS and DFS was strengthened when the analysis was limited to patients with stage I disease (P = 0.005 and P=0.003 respectively).
NKX2-1 expression impacts prognosis in early-stage NSCLC patients, particularly in those with neither TP53 nor KRAS mutations.
NKX2-1 是肺发育过程中的关键分子，在非小细胞肺癌（NSCLC）中高度表达，尤其是在肺腺癌（ADK）中，它是一种诊断标志物。研究 NKX2-1 在 NSCLC 中的预后作用的报告得出了相互矛盾的结果。有两种 microRNA（miRNA）与 NKX2-1 相关：miR-365，它是 NKX2-1 的靶点；miR-33a，它是 NKX2-1 的下游分子。我们在一组早期 NSCLC 患者和根据 TP53、KRAS 和 EGFR 突变状态分类的患者亚组中检查了 NKX2-1、miR-365 和 miR-33a 对生存的影响。
使用 TaqMan 测定法在 110 例早期 NSCLC 患者中测定 mRNA 和 miRNA 的表达。通过 Sanger 测序评估 TP53、KRAS 和 EGFR 突变。
NKX2-1 在从不吸烟者（P=0.017）、ADK（P<0.0001）和野生型 TP53 患者（P=0.001）中表达上调。发现 NKX2-1 表达与 miR-365 表达呈负相关（ρ=-0.287；P=0.003），但 NKX2-1 与 miR-33a 表达无相关性。NKX2-1 高表达的患者总生存期（OS）长于低表达的患者（80.8 与 61.2 个月（P=0.035），而 miR-365 水平低的患者 OS 有延长趋势（P=0.07）。在没有 TP53 或 KRAS 突变的患者中，NKX2-1 对 OS 和 DFS 的影响更高。NKX2-1 高表达与 OS（77.6 与 54 个月；P=0.017）和 DFS（74.6 与 57.7 个月；P=0.006）相关，高于低表达。当分析仅限于 I 期疾病患者时，NKX2-1 与 OS 和 DFS 的关联得到加强（P=0.005 和 P=0.003）。
NKX2-1 的表达影响早期 NSCLC 患者的预后，特别是在没有 TP53 或 KRAS 突变的患者中。
