IMDEA Food Institute, CEI UAM + CSIC, Madrid 28702, Spain.
12 de Octubre University Hospital, Madrid 28041, Spain.
Cancer Biol Med. 2020 May 15;17(2):444-457. doi: 10.20892/j.issn.2095-3941.2019.0363.
Long-term survivors (LS) of non-small cell lung cancer (NSCLC) without driver alterations, displaying an overall survival (OS) of more than 3 years, comprise around 10% of cases in several series treated with chemotherapy. There are classical prognosis factors for these cases [stage, Eastern Cooperative Oncology Group (ECOG), etc.], but more data are required in the literature. In this multi-center study, we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular characterization. In the first step, we conducted a clinical-pathological characterization of the patients. Afterwards, we carried out a genetic analysis by comparing LS to a sample of short-term survivors (SS) (with an OS less than 9 months). We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS, and later confirmed these with reverse transcription-polymerase chain reaction (RT-PCR) for the rest of the samples. A total of 94 patients were included, who were mainly men, former smokers, having adenocarcinoma (AC)-type NSCLC with an ECOG of 0-1. We obtained an initial differential transcriptome expression, displaying 5 over- and 33 under-expressed genes involved in different pathways: namely, the secretin receptor, surfactant protein, trefoil factor 1 (TFF1), serpin, Ca-channels, and Toll-like receptor (TLRs) families. Finally, RT-PCR analysis of 40 (20 LS/20 SS) samples confirmed that four genes (surfactant proteins and SFTP) were significantly down-regulated in SS compared to LS by using an analysis of covariance (ANCOVA) model: ( = 0.023), ( = 0.027), ( = 0.02), and ( = 0.047). We present a sequential genetic analysis of a sample of NSCLC LS with no driver alterations, obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.
非小细胞肺癌（NSCLC）无驱动改变的长期幸存者（LS），在接受化疗的几项研究中，其总生存期（OS）超过 3 年，占 10%左右。这些病例有经典的预后因素[分期、东部肿瘤协作组（ECOG）等]，但文献中需要更多的数据。在这项多中心研究中，我们专注于 OS 超过 36 个月的晚期 NSCLC 的 LS，进行临床病理和分子特征分析。首先，我们对患者进行了临床病理特征分析。然后，我们通过将 LS 与短期幸存者（SS）（OS 小于 9 个月）的样本进行比较，进行了遗传分析。我们最初使用全基因组 RNA-seq 来识别 LS 和 SS 的差异表达谱，然后用剩余样本的逆转录-聚合酶链反应（RT-PCR）来验证这些差异表达谱。共纳入 94 例患者，主要为男性，为前吸烟者，患有 ECOG 0-1 的腺癌（AC）型 NSCLC。我们获得了一个初始的差异转录组表达谱，显示 5 个上调和 33 个下调基因涉及不同的途径：即分泌素受体、表面蛋白、三叶因子 1（TFF1）、丝氨酸蛋白酶抑制剂、钙通道和 Toll 样受体（TLRs）家族。最后，对 40 例（20 例 LS/20 例 SS）样本进行 RT-PCR 分析，通过协方差分析（ANCOVA）模型，发现 SS 中 4 个基因（表面蛋白和 SFTP）明显下调，与 LS 相比，差异有统计学意义： （ = 0.023）， （ = 0.027）， （ = 0.02）和 （ = 0.047）。我们对无驱动改变的 NSCLC LS 样本进行了一系列的遗传分析，获得了差异 RNA-seq/RT-PCR 谱，显示 SF 基因的异常表达。
