Department of Clinical Oncology, Juntendo University Graduate School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan.
Department of Cancer Genome Research, Sasaki Institute, Sasaki Foundation, Kandasurugadai, Chiyoda-ku, Tokyo, Japan.
Sci Rep. 2020 Apr 10;10(1):6214. doi: 10.1038/s41598-020-63200-7.
Many driver pathways for cancer cell proliferation have been reported. Driver pathway activation is often evaluated based on a single hotspot mutation such as EGFR L858R. However, because of complex intratumoral networks, the impact of a driver pathway cannot be predicted based on only a single gene mutation. Here, we developed a novel diagnostic system named the "EGFR impact score" which is based on multiplex mRNA expression profiles, which can predict the impact of the EGFR pathway in lung cancer cells and the effect of EGFR-tyrosine kinase inhibitors on malignancy. The EGFR impact score indicated robust predictive power for the prognosis of early-stage lung cancer because this score can evaluate the impact of the EGFR pathway on the tumor and genomic instability. Additionally, the molecular features of the poor prognostic group resembled those of biomarkers associated with immune checkpoint inhibitors. The EGFR impact score is a novel prognostic and therapeutic indicator for lung adenocarcinoma.
已经报道了许多促进癌细胞增殖的驱动途径。驱动途径的激活通常基于单个热点突变(如 EGFR L858R)进行评估。然而,由于肿瘤内的复杂网络,仅基于单个基因突变无法预测驱动途径的影响。在这里,我们开发了一种名为“EGFR 影响评分”的新型诊断系统,该系统基于多重 mRNA 表达谱,可以预测肺癌细胞中 EGFR 途径的影响以及 EGFR-酪氨酸激酶抑制剂对恶性肿瘤的影响。EGFR 影响评分对早期肺癌的预后具有强大的预测能力,因为该评分可以评估 EGFR 途径对肿瘤和基因组不稳定性的影响。此外,预后不良组的分子特征与免疫检查点抑制剂相关的生物标志物相似。EGFR 影响评分是肺腺癌的一种新的预后和治疗指标。