Identification of Estrogen-Related Genes in Breast Cancer: The Malaysian Context

ABSTRACT

Estrogen receptor (ER) status is an important indicator used to predict hormone responsiveness and survival rate of breast cancer patients. Breast cancer patients with estrogen receptor positive (ER+) tumors are more likely to benefit from endocrine therapies and have better prognosis than those with estrogen receptor negative (ER-) tumors. Approximately 30% of the patients with ER+ phenotype do not benefit from anti-estrogen therapies. This circumstance suggests that additional biomarkers are needed to predict and improve the treatment strategies in breast cancer patients. We analyzed 28 ER+ and 18 ER- tumors to evaluate their gene expression patterns. We identified 180 differentially expressed genes in ER+ compared to the ER- group at 99% confidence interval level. Out of the 180 genes, 79 and 94 genes were determined respectively as positive and negative significant genes in Significance Analysis of Microarray (SAM). Eleven out of the 79 significant positive genes were more than two ( > 2) fold change. The differentially expressed genes identified in the ER+ group included CADM4, CD151, GATA3, Wnt2, PGR, TFF1 and TFF3. We randomly selected two genes, namely CD151 and LPIN1 for verification by Taqman qRT-PCR. Our qRT-PCR result is reproducible and comparable with the microarray data. Our preliminary findings revealed potential estrogen-responsive genes such as CADM4, CD151 and GATA3, which might play a crucial role in ER+ breast cancer development and progression in the Malaysian population. More extensive studies are however needed to investigate the role of these genes in the carcinogenesis of estrogen related breast cancers.