First People's Hospital, Wujiang, Jiangsu, China.
Eur Rev Med Pharmacol Sci. 2013 Aug;17(16):2159-65.
Breast cancer remains a major health problem even with all the recent technological advancements. Large-scale gene expression analysis has offered great ease for both biological characterization and therapeutic planning of breast cancer. Previous studies mostly used variance/regression analysis, which becomes fundamentally flawed when there are unaccounted array specific factors. Here we aim to investigate the underlying mechanism of breast cancer through partial least squares (PLS) based gene expression profile analysis.
With a gene expression profile data set downloaded from the Gene Expression Omnibus database, we performed PLS based analysis.
We acquire 932 and 771 differentially expressed genes (DEGs) in breast cancer metastasis of estrogen-receptor (ER)-positive and ER-negative patients, respectively. For ER-positive patients, 32 pathways were found to be enriched with DEGs, including immune related pathways, cellular processes and environmental information processing pathways. Survival analysis demonstrated that 18 of them were closely related with non-recurrence rate along time after surgery. For ER negative patients, only three pathways including the folate biosynthesis pathway were enriched with DEGs and none of them overlapped with those of ER positive patients. Only the cholinergic synapse pathway was significantly associated with the non-recurrence rate according to the survival analysis.
Our findings shed light on pathways involved in breast cancer relapse with the hope to give some theoretical supports for further therapeutic study.
尽管最近取得了许多技术进步,但乳腺癌仍然是一个重大的健康问题。大规模基因表达分析为乳腺癌的生物学特征和治疗计划提供了极大的便利。以前的研究大多使用方差/回归分析,但当存在未被考虑的阵列特定因素时,这种方法就会出现根本缺陷。在这里,我们旨在通过基于偏最小二乘(PLS)的基因表达谱分析来研究乳腺癌的潜在机制。
我们从基因表达综合数据库下载了一个基因表达谱数据集,并进行了基于 PLS 的分析。
我们分别在雌激素受体(ER)阳性和 ER 阴性乳腺癌转移患者中获得了 932 个和 771 个差异表达基因(DEG)。对于 ER 阳性患者,发现 32 条途径与 DEG 富集有关,包括免疫相关途径、细胞过程和环境信息处理途径。生存分析表明,其中 18 条途径与手术后随时间推移的非复发率密切相关。对于 ER 阴性患者,只有三条途径(包括叶酸生物合成途径)与 DEG 富集有关,并且它们与 ER 阳性患者的途径没有重叠。只有胆碱能突触途径与非复发率根据生存分析有显著关联。
我们的研究结果揭示了乳腺癌复发相关的途径,希望为进一步的治疗研究提供一些理论支持。