Huang Ching-Shui, Tsai Ming-Lin, Lu Tzu-Pin, Tu Chao-Chiang, Liu Chih-Yi, Huang Chi-Jung, Ho Yuan-Soon, Tu Shih-Hsin, Chuang Eric Y, Tseng Ling-Ming, Huang Chi-Cheng
Division of General Surgery, Department of Surgery, Cathay General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Division of General Surgery, Department of Surgery, Cathay General Hospital, Taipei, Taiwan.
J Formos Med Assoc. 2022 Oct;121(10):1945-1955. doi: 10.1016/j.jfma.2022.01.022. Epub 2022 Feb 16.
BACKGROUND/PURPOSE: Previously we had identified concurrent genes, which highlighted the interplay between copy number variation (CNV) and differential gene expression (GE) for Han Chinese breast cancers. The merit of the approach is to discovery biomarkers not identifiable by conventional GE only data, for which phenotype-correlation or gene variability is the criteria of gene selection.
Thirty-one comparative genomic hybridization (CGH) and 83 GE microarrays were performed, with 29 breast cancers assayed from both platforms. Potential targets were revealed by Genomic Identification of Significant Targets in Cancer (GISTIC) from CGH arrays. Concurrent genes and genes with significant GISTIC scores were used to derive the extended concurrent genes signature, which was consensus from leading edge analysis across all studies and a supervised partial least square (PLS) regression predictive model of disease-free survival was constructed.
There were 1584 concurrent genes from 29 samples with both CGH and GE microarrays. Enriched concurrent genes sets for disease-free survival were identified independently from 83 GE arrays and another one with Han Chinese origin as well as three studies of Western origin. For five studies with disease-free survival follow up, prognostic discrepancy was observed between predicted high-risk and low-risk group patients.
We concluded that through parallel analyses of CGH and GE microarrays, the proposed extended concurrent gene expression signature can identify biomarkers with prognostic values.
背景/目的:此前我们已鉴定出并发基因,这些基因突出了汉族乳腺癌中拷贝数变异(CNV)与差异基因表达(GE)之间的相互作用。该方法的优点是能够发现仅通过传统GE数据无法识别的生物标志物,其基因选择标准是表型相关性或基因变异性。
进行了31次比较基因组杂交(CGH)和83次GE微阵列分析,对29例乳腺癌进行了两种平台的检测。通过CGH阵列的癌症重要靶点基因组鉴定(GISTIC)揭示潜在靶点。使用并发基因和具有显著GISTIC评分的基因来推导扩展并发基因特征,这是所有研究前沿分析的共识,并构建了无病生存的监督偏最小二乘(PLS)回归预测模型。
来自29个同时进行CGH和GE微阵列检测样本的有1584个并发基因。分别从83个GE阵列、另一个汉族来源的阵列以及三项西方来源的研究中独立鉴定出与无病生存相关的富集并发基因集。对于五项有无病生存随访的研究,观察到预测的高危和低危组患者之间存在预后差异。
我们得出结论,通过对CGH和GE微阵列的平行分析,所提出的扩展并发基因表达特征能够识别具有预后价值的生物标志物。