Wu Ruxing, Liu Tao, Yang Peiwen, Liu Xiyou, Liu Fei, Wang Ya, Xiong Huihua, Yu Shiying, Huang Xiaoyuan, Zhuang Liang
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service, Emory University School of Medicine, Atlanta, GA, USA.
Oncotarget. 2017 Apr 4;8(14):22842-22853. doi: 10.18632/oncotarget.15280.
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.
为了探究肥胖恶化乳腺癌预后的新机制,我们重新分析了正常、超重和肥胖乳腺癌患者的基因表达数据,以探索潜在基因,并通过临床和实验数据验证其功能。15-羟基前列腺素脱氢酶(HPGD)基因的倍数变化在肥胖患者与正常体重患者中呈下降趋势,肥胖患者与正常体重患者相比为0.46。HPGD蛋白在正常体重组中表达最高,在肥胖组中表达最低。HPGD低表达组的阳性淋巴结率为67%,HPGD高表达组为35%。HPGD低表达组与高表达组的5年无复发生存率(RFS)和总生存率(OS)有显著差异。肥胖显著降低了5年的RFS率和OS率。HPGD表达下调可增加乳腺癌细胞系MCF-7的迁移和增殖能力。综上所述,我们的结果表明HPGD低表达可能是肥胖乳腺癌患者预后不良的一个原因。