Abstract
In order to explore the new mechanism that obesity worsens the prognosis of breast cancer, we reanalyzed the data about gene expression of normal, overweight, and obese breast cancer patients to explore potential genes and validate its function by clinical and experimental data. The fold change of 15-hydroxyprostaglandin dehydrogenate (HPGD) gene which displayed declining trend with BMI increase was 0.46 in obese versus normal weight patients. HPGD protein was highest expressed in normal weight group and lowest expressed in obese group. The rate of positive lymph nodes was 67% in low expression of HPGD group and 35% in high expression of HPGD group. The recurrence-free survival (RFS) rate and overall survival (OS) rate of 5 years had significant difference between low expression of HPGD group and high expression of HPGD group. Obesity dramatically decreased the RFS rate and OS rate of 5 years. Down regulation of HPGD expression could increase the migration and proliferation ability of breast cancer cell line MCF-7. Taken together, our results indicate that low expression of HPGD may be a reason for poor prognosis of obese breast cancer patients.
Highlights
Breast cancer accounts for 23% of all cancer cases and is the common cause of cancer death [1].Females with body mass index (BMI) increased are found to be more risk of developing breast cancer [2]
Our results indicate that low expression of hydroxyprostaglandin dehydrogenate (HPGD) may be a reason for poor prognosis of obese breast cancer patients
Since profile No 9 has declining trend pattern from normal weight to overweight to obese group (Figure 1B).We combined the genes with the fold change ≤ 0.5, in profiles No 9, and in the five ahead significant pathways of down regular genes in obese versus normal weight group to screen the differentially expressed genes (DEGs) (Figure 1C, 1D)
Summary
Breast cancer accounts for 23% of all cancer cases and is the common cause of cancer death [1].Females with body mass index (BMI) increased are found to be more risk of developing breast cancer [2]. An increased recurrence rate and a decreased survival rate in breast cancer is consistently related to obesity [3,4,5]. The mechanism of how obesity affects the prognosis of breast cancer is complex. It’s well known that obese women have hyperinsulinemia or insulin resistance, and whose adipose tissues secrete adiponectin, estrogen, leptin, and incalculable less well-characterized epithelial cell mitogen. These factors may stimulate breast tumor evolution [6, 7]. To further study the correlation between BMI and breast cancer, Creighton et al have evaluated gene expression of normal, overweight, and obese breast cancer patients and suggested that obesity down-regulated or up-regulated the gene expression patterns of breast cancer patients [8]
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