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印度女性乳腺癌基因表达谱研究。

Study of Gene Expression Profiles of Breast Cancers in Indian Women.

机构信息

Tumour Biology Division, ICMR-National Institute of Pathology, New Delhi, 110029, India.

Bioinformatics Cell, ICMR-National Institute of Pathology, New Delhi, 110029, India.

出版信息

Sci Rep. 2019 Jul 10;9(1):10018. doi: 10.1038/s41598-019-46261-1.

Abstract

Breast cancer is the most common cancer among women globally. In India, the incidence of breast cancer has increased significantly during the last two decades with a higher proportion of the disease at a young age compared to the west. To understand the molecular processes underlying breast cancer in Indian women, we analysed gene expression profiles of 29 tumours and 9 controls using microarray. In the present study, we obtained 2413 differentially expressed genes, consisting of overexpressed genes such as COL10A1, COL11A1, MMP1, MMP13, MMP11, GJB2, and CST1 and underexpressed genes such as PLIN1, FABP4, LIPE, AQP7, LEP, ADH1A, ADH1B, and CIDEC. The deregulated pathways include cell cycle, focal adhesion and metastasis, DNA replication, PPAR signaling, and lipid metabolism. Using PAM50 classifier, we demonstrated the existence of molecular subtypes in Indian women. In addition, qPCR validation of expression of metalloproteinase genes, MMP1, MMP3, MMP11, MMP13, MMP14, ADAMTS1, and ADAMTS5 showed concordance with that of the microarray data; wherein we found a significant association of ADAMTS5 down-regulation with older age (≥55 years) of patients. Together, this study reports gene expression profiles of breast tumours from the Indian subcontinent, throwing light on the pathways and genes associated with the breast tumourigenesis in Indian women.

摘要

乳腺癌是全球女性中最常见的癌症。在印度,过去二十年乳腺癌的发病率显著上升,与西方相比,该病发病年龄更年轻,比例更高。为了了解印度女性乳腺癌的分子发病机制,我们使用微阵列分析了 29 个肿瘤和 9 个对照的基因表达谱。在本研究中,我们获得了 2413 个差异表达基因,包括 COL10A1、COL11A1、MMP1、MMP13、MMP11、GJB2 和 CST1 等过表达基因和 PLIN1、FABP4、LIPE、AQP7、LEP、ADH1A、ADH1B 和 CIDEC 等低表达基因。失调的途径包括细胞周期、焦点粘连和转移、DNA 复制、PPAR 信号和脂质代谢。使用 PAM50 分类器,我们证明了印度女性中存在分子亚型。此外,对 MMP1、MMP3、MMP11、MMP13、MMP14、ADAMTS1 和 ADAMTS5 等金属蛋白酶基因表达的 qPCR 验证与微阵列数据一致;我们发现 ADAMTS5 下调与患者年龄(≥55 岁)较大显著相关。总之,本研究报告了来自印度次大陆的乳腺肿瘤的基因表达谱,揭示了与印度女性乳腺肿瘤发生相关的途径和基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9847/6620270/d9fde6f3499a/41598_2019_46261_Fig1_HTML.jpg

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