Brodie Seth A, Li Ge, Brandes Johann C
Atlanta VAMC, USA; Department of Hematology and Medical Oncology, Emory University, USA; Winship Cancer Institute, Emory University, USA.
Department of Hematology and Medical Oncology, Emory University, USA; Winship Cancer Institute, Emory University, USA.
Respir Med. 2015 Jan;109(1):131-6. doi: 10.1016/j.rmed.2014.11.004. Epub 2014 Nov 21.
CHFR expression has previously been established as a powerful predictor for response to taxane based first-line chemotherapy in non-small cell lung cancer. It is currently unknown however, if reduced CHFR expression correlates with certain molecular subtypes of lung cancer.
In order to determine which patients may benefit from CHFR biomarker testing we conducted the present study to characterize clinical and molecular characteristics of patients with reduced vs. high CHFR expression.
We utilized the extensive molecular and clinical data of the most recent adeno- and squamous cell carcinoma datasets from The Cancer Genome Atlas (TCGA) project. CHFR expression, analyzed by RNA-seq, was classified as high vs. low based on the median CHFR expression level and correlated with the presence or absence of lung cancer specific mutations (EGFR, KRAS, ALK, MET, ERBB2, TP53, STK11, ROS1, RET, NF1, Pik3CA for adenocarcinomas and FGFR1, FGFR2, FGFR3, TP53, STK11, EGFR for squamous cell carcinomas).
Reduced CHFR expression was associated with EGFR exon19/21 mutations in adenocarcinoma OR 0.23 (95%CI: 0.06-0.88) and male gender in squamous cell carcinoma (OR 0.46 (95%CI 0.23-0.92), p = 0.02).
CHFR表达先前已被确立为非小细胞肺癌中基于紫杉烷的一线化疗反应的有力预测指标。然而，目前尚不清楚CHFR表达降低是否与肺癌的某些分子亚型相关。
为了确定哪些患者可能从CHFR生物标志物检测中获益，我们开展了本研究，以表征CHFR表达降低与高表达患者的临床和分子特征。
我们利用了癌症基因组图谱（TCGA）项目中最新的腺癌和鳞癌数据集的广泛分子和临床数据。通过RNA测序分析的CHFR表达，根据CHFR表达水平中位数分为高表达与低表达，并与肺癌特异性突变（腺癌为EGFR、KRAS、ALK、MET、ERBB2、TP53、STK11、ROS1、RET、NF1、Pik3CA；鳞癌为FGFR1、FGFR2、FGFR3、TP53、STK11、EGFR）的存在与否相关联。
CHFR表达降低与腺癌中的EGFR外显子19/21突变相关（比值比0.23，95%置信区间：0.06 - 0.88），与鳞癌中的男性性别相关（比值比0.46，95%置信区间0.23 - 0.92，p = 0.02）。
