Peñate Xenia, Praena-Fernández Juan Manuel, Romero Pareja Pedro, Enguix-Riego María Del Valle, Payán-Bravo Laura, Vieites Begoña, Gomez-Izquierdo Lourdes, Jaen Olasolo Javier, Rivin Del Campo Eleonor, Reyes Jose Carlos, Chávez Sebastián, Lopez Guerra Jose Luis
Instituto de Biomedicina de Sevilla, Universidad de Sevilla-CSIC-Hospital Universitario V. del Rocío, Avda. Manuel Siurot s/n, 41013 Seville, Spain.
Department of Nursing, Universidad de Sevilla, 41009 Seville, Spain.
Cancers (Basel). 2020 Apr 24;12(4):1052. doi: 10.3390/cancers12041052.
Canonical prefoldin is a protein cochaperone composed of six different subunits (PFDN1 to 6). PFDN1 overexpression promotes epithelial-mesenchymal transition (EMT) and increases the growth of xenograft lung cancer (LC) cell lines. We investigated whether this putative involvement of canonical PFDN in LC translates into the clinic. First, the mRNA expression of 518 non-small cell LC (NSCLC) cases from The Cancer Genome Atlas (TCGA) database was evaluated. Patients with overexpression had lower overall survival (OS; 45 vs. 86 months; = 0.034). We then assessed the impact of PFDN expression on outcome in 58 NSCLC patients with available tumor tissue samples. PFDN1, 3, and 5 overexpression were found in 38% ( = 22), 53% ( = 31), and 41% ( = 24) of tumor samples. PFDN1, 3, and 5 overexpression were significantly associated with lower OS, lower disease-free survival (DFS), and lower distant metastasis-free survival (DMFS) for PFDN1 and 3 with a trend for PFDN5. In multivariate analysis, PFDN5 retained significance for OS (hazard ratio (HR) 2.56; = 0.007) and PFDN1 for DFS (HR 2.53; = 0.010) and marginally for DMFS (HR 2.32; = 0.053). Our results indicate that protein response markers, such as PFDN1, 3, and 5, may complement mRNA signatures and be useful for determining the most appropriate therapy for NSCLC patients.
典型预折叠蛋白是一种由六个不同亚基（PFDN1至6）组成的蛋白质伴侣分子。PFDN1过表达促进上皮-间质转化（EMT）并增加异种移植肺癌（LC）细胞系的生长。我们研究了典型PFDN在LC中的这种假定作用是否转化到临床中。首先，评估了来自癌症基因组图谱（TCGA）数据库的518例非小细胞肺癌（NSCLC）病例的mRNA表达。过表达的患者总生存期（OS；45对86个月；P = 0.034）较低。然后，我们评估了PFDN表达对58例有可用肿瘤组织样本的NSCLC患者预后的影响。在38%（n = 22）、53%（n = 31）和41%（n = 24）的肿瘤样本中发现了PFDN1、3和5的过表达。PFDN1、3和5的过表达与较低的OS、较低的无病生存期（DFS）以及PFDN1和3较低的无远处转移生存期（DMFS）显著相关，PFDN5有相关趋势。在多变量分析中，PFDN5对OS仍具有显著性（风险比（HR）2.56；P = 0.007），PFDN1对DFS具有显著性（HR 2.53；P = 0.010），对DMFS有边缘显著性（HR 2.32；P = 0.053）。我们的结果表明，蛋白质反应标志物，如PFDN1、3和5，可能补充mRNA特征，并有助于确定NSCLC患者最合适的治疗方法。
