乳腺癌癌旁组织特异性表达基因分析

doi:10.16288/j.yczz.19-099

遗传 ›› 2019, Vol. 41 ›› Issue (7): 625-633.doi: 10.16288/j.yczz.19-099

乳腺癌癌旁组织特异性表达基因分析

禹奇超^1,²,宋彬^1,²,邹轩轩^1,^2,³,王岭⁴,刘德权⁵,李波^1,²,马昆^1,²()

^1. 深圳华大生命科学研究院,深圳 518083
^2. 深圳国家基因库,深圳 518120
^3. 中国科学院大学华大教育中心,深圳 518083
^4. 第四军医大学西京医院血管内分泌外科,西安 710033
^5. 云南省肿瘤医院,昆明医科大学第三附属医院乳腺外科,昆明 650118

收稿日期:2019-04-09 修回日期:2019-05-15 出版日期:2019-07-20 发布日期:2019-05-23
通讯作者: 马昆 E-mail:makun1@genomics.cn
作者简介:禹奇超,硕士,专业方向：肿瘤基因组学与生物信息学。E-mail:yuqichao@genomics.cn|宋彬,硕士,专业方向：肿瘤基因组学与生物信息学。E-mail:songbin@genomics.cn
基金资助:
深圳市科创委项目(JCYJ20150629114130814);深圳市工信局项目资助(20170731162715261)

Analysis of normal tissues adjacent to the tumour-specific expressed genes in breast cancer

Yu Qichao^1,²,Song Bin^1,²,Zou Xuanxuan^1,^2,³,Wang Ling⁴,Liu Dequan⁵,Li Bo^1,²,Ma Kun^1,²()

^1. BGI-Shenzhen, Shenzhen 518083, China
^2. China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China
^3. BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China
^4. Department of Vascular and Endocrine Surgery, Xijing Hospital of Fourth Military Medical University, Xi'an 710033, China
^5. Department of Mammary Surgery, Yunnan Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China

Received:2019-04-09 Revised:2019-05-15 Online:2019-07-20 Published:2019-05-23
Contact: Ma Kun E-mail:makun1@genomics.cn
Supported by:
Supported by Science, Technology and Innovation Commission of Shenzhen Municipality(JCYJ20150629114130814);Shenzhen Municipal Government of China(20170731162715261)

摘要/Abstract

摘要：

癌症研究中常用癌旁组织(normal tissues adjacent to the tumour, NAT)作对照,而癌旁组织与无肿瘤的正常组织的基因表达谱是有差异的。癌旁组织特异性表达基因的存在通常会干扰传统的转录图谱研究,然而目前关于癌旁与无肿瘤组织的基因表达谱差异的研究相对较少。本研究对14例乳腺癌患者的癌组织、癌旁组织和对侧正常乳腺组织样本进行高深度RNA测序和分析,发现癌旁组织相比对侧正常乳腺组织有102个差异表达基因。基因富集和蛋白-蛋白互作分析揭示这些差异表达基因显著富集在肿瘤坏死因子(tumour necrosis factor, TNF)和上皮间质转化(epithelial-mesenchymal transition, EMT)等癌症相关的基因集中。通过比较癌旁组织与癌组织、癌旁组织与对侧正常乳腺组织的转录图谱,发现23个癌旁组织特异性高表达的基因,即癌旁特异性激活(tumour-adjacent speci?c activation, TASA)基因。这些基因显著富集在TNF基因集中,其中15个是新发现的基因。结果表明,TASA基因在乳腺癌癌旁组织中普遍存在,并且与免疫系统的TNF信号有关。癌旁中存在类肿瘤型表达模式的基因,这些基因可能与肿瘤形成有关,但是往往在肿瘤-癌旁成对研究中被遗漏。

关键词: 乳腺癌, 癌旁特异激活基因, RNA测序, 基因表达谱

Abstract:

Normal tissues adjacent to the tumour (NAT) are widely used as controls in comparative studies to search for cancer-associated genes. However, the gene expression profiles between NAT and non-tumour-bearing tissues are different. The presence of NAT-specific expressed genes often hinders traditional transcriptional profiles studies. Further, studies on the differences in gene expression profiles between NAT and tumour-free tissues are infrequently performed. In this study, we sequenced and analysed the transcriptomes of tumour tissues (T), matched NAT and contralateral breast normal tissues (CBN) of 14 breast cancer patients, and identified 102 differentially expressed genes (DEGs) between CBN and NAT. Gene enrichment and protein-protein interaction (PPI) analyses revealed that these DEGs are significantly enriched in TNF (tumour necrosis factor) signalling and EMT (epithelial-mesenchymal transition) gene sets closely associated with oncogenesis. Comparative analyses of the transcriptomic profiles between NAT and CBN, NAT and T identified 23 NAT-specific highly-expressed genes, namely tumour-adjacent speci?cally activated (TASA) genes. These genes were significantly enriched in TNF signalling gene set, and 15 of which have not been previously reported. The results indicate that TASA genes are common in adjacent tissues and are related to the TNF signalling in the immune system. The tumour-adjacent tissues harbour tumour-like expressed genes that could contribute to tumour initiation but are often missed in NAT-T pair-wise studies.

Key words: breast cancer, TASA gene, RNA-sequencing, gene expression profile

禹奇超,宋彬,邹轩轩,王岭,刘德权,李波,马昆. 乳腺癌癌旁组织特异性表达基因分析[J]. 遗传, 2019, 41(7): 625-633.

Yu Qichao,Song Bin,Zou Xuanxuan,Wang Ling,Liu Dequan,Li Bo,Ma Kun. Analysis of normal tissues adjacent to the tumour-specific expressed genes in breast cancer[J]. Hereditas(Beijing), 2019, 41(7): 625-633.

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乳腺癌癌旁组织特异性表达基因分析

Analysis of normal tissues adjacent to the tumour-specific expressed genes in breast cancer

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