Downregulation of the circadian clock gene period 2 aggravates prognosis in breast cancer patients with obesity  

作　　者：Ru-Xing Wu Dan Hu Han-Wang Zhang Xiao-Yuan Huang Liang Zhuang 

机构地区：[1]Reproductive Medicine Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [2]Cancer Biology Research Centre,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [3]Cancer Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China

出　　处：《Oncology and Translational Medicine》2024年第2期73-78,共6页肿瘤学与转化医学（英文版）

摘　　要：Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with obesity.Methods:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate genes.Subsequently,we validated the protein levels of these candidates using immunohistochemistry.Finally,we investigated the association between candidate genes and breast cancer prognosis at Tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression models.Results:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight patients.The expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,respectively.The 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(P<0.05).Furthermore,the 8-year recurrence-free survival rates were 66.2%and 76.4%,and the 8-year overall survival rates were 79.9%and 86.3%in the low and high PER2 expression groups,respectively(P<0.05).The unadjusted hazard ratio for PER2 was 1.550(95%confidence interval,1.029–2.335),and the adjusted hazard ratio was 3.003(95%confidence interval,1.838–4.907).Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.

关 键 词：Breast cancer OBESITY PER2 PROGNOSIS 

分 类 号：R737.9[医药卫生—肿瘤]