Lin Ching-Hung, Huang Ruby Yun-Ju, Lu Tzu-Pin, Kuo Kuan-Ting, Lo Ko-Yun, Chen Ching-Hsuan, Chen I-Chun, Lu Yen-Shen, Chuang Eric Y, Thiery Jean Paul, Huang Chiun-Sheng, Cheng Ann-Lii
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Department of Medical Oncology, National Taiwan University Cancer Center Hospital, Taipei, Taiwan.
NPJ Breast Cancer. 2021 Jul 5;7(1):88. doi: 10.1038/s41523-021-00299-5.
In East Asia, the breast cancer incidence rate among women aged <50 years has rapidly increased. Emerging tumors are distinctly characterized by a high prevalence of estrogen receptor (ER)-positive/human epidermal growth factor receptor (HER2)-negative cancer. In the present study, we identified unique genetic alterations in these emerging tumors. We analyzed gene copy number variations (CNVs) in breast tumors from 120 Taiwanese patients, and obtained public datasets of CNV and gene expression (GE). The data regarding CNV and GE were separately compared between East Asian and Western patients, and the overlapping genes identified in the comparisons were explored to identify the gene-gene interaction networks. In the age <50 years/ER + /HER2- subgroup, tumors of East Asian patients exhibited a higher frequency of copy number loss in APOA1/C3/A4/A5, a lipid-metabolizing gene cluster (33 vs. 10%, P < .001) and lower APOA1/C3/A4/A5 expressions than tumors of Western patients. These copy number loss related- and GE-related results were validated in another Taiwanese cohort and in two GE datasets, respectively. The copy number loss was significantly associated with poor survival among Western patients, but not among East Asian patients. Lower APOA1, APOC3, and APOA5 expressions were associated with higher ESTIMATE immune scores, indicating an abundance of tumor-infiltrating immune cells. In conclusion, APOA1/C3/A4/A5 copy number loss was more prevalent in luminal breast tumors among East Asian women aged <50 years, and its immunomodulatory effect on the tumor microenvironment possibly plays various roles in the tumor biology of East Asian patients.
在东亚,50岁以下女性的乳腺癌发病率迅速上升。新出现的肿瘤明显特征是雌激素受体(ER)阳性/人表皮生长因子受体(HER2)阴性癌症的高患病率。在本研究中,我们在这些新出现的肿瘤中鉴定出独特的基因改变。我们分析了120名台湾患者乳腺肿瘤中的基因拷贝数变异(CNV),并获得了CNV和基因表达(GE)的公共数据集。分别比较了东亚和西方患者之间关于CNV和GE的数据,并探索了比较中鉴定出的重叠基因以识别基因-基因相互作用网络。在年龄<50岁/ER+/HER2-亚组中,东亚患者的肿瘤在载脂蛋白A1/C3/A4/A5(一个脂质代谢基因簇)中出现拷贝数缺失的频率更高(33%对10%,P<.001),且与西方患者的肿瘤相比,APOA1/C3/A4/A5表达更低。这些与拷贝数缺失相关和与GE相关的结果分别在另一个台湾队列和两个GE数据集中得到验证。拷贝数缺失与西方患者的不良生存显著相关,但与东亚患者无关。较低的APOA1、APOC3和APOA5表达与较高的ESTIMATE免疫评分相关,表明肿瘤浸润免疫细胞丰富。总之,APOA1/C3/A4/A5拷贝数缺失在<50岁的东亚女性的管腔型乳腺肿瘤中更为普遍,其对肿瘤微环境的免疫调节作用可能在东亚患者的肿瘤生物学中发挥多种作用。
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