Gene expression abnormalities in histologically normal breast epithelium of breast cancer patients
Gene expression abnormalities in histologically normal breast epithelium of breast cancer patients
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DOI：
10.1002/ijc.23267
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发表时间：
2008-04-01
影响因子：
6.4
通讯作者：
Rosenberg, Carol L.
中科院分区：
文献类型：
--
作者：
Tripathi, Anusri;King, Chialin;Rosenberg, Carol L.
癌症患者表面正常的上皮可能隐藏着基因异常。全面比较组织学正常乳腺癌患者和无癌对照组乳腺上皮基因表达的数据有限。本研究比较了这些群体之间的整体基因表达。我们使用来自两组显微解剖组织学上正常的终末导管小叶单位（TDLU）的RNA进行了微阵列检测：(i)癌症正常（CN） （TDLU与未治疗的ER+乳腺癌相邻（n = 14））和（ii）乳房缩小成形术（RM）（年龄匹配的无乳腺疾病女性的TDLU (n = 15)）。Cyber-T识别了差异表达基因。定量RT-PCR （qRT-PCR）、免疫组化（IHC）以及与包括6例原位癌（CIS）在内的独立微阵列数据的比较验证了结果。基因本体（GO）、UniProt和已发表的文献评估基因功能。CN与RM之间差异表达约127个probesset，对应1.05个基因（p < 0.0009，对应FDR < 0.10）。104/127（82%）的问题集在CIS和RM之间也有差异表达，几乎总是（102/104(98%)）与CN与RM的方向相同。在这105个基因中，有三分之二先前与致癌有关。过度代表的功能群包括转录，g蛋白偶联和趋化因子受体活性，MAPK级联和即时早期基因。这些类别中的大多数基因在CN与RM中表达不足。我们得出结论，整体基因表达异常存在于乳腺癌患者的正常上皮中，也存在于早期癌症中。因此，正常上皮中的癌症相关通路可能受到干扰。这些异常可能是疾病风险、隐匿性疾病或组织对现有肿瘤反应的标志。(c) 2007 Wiley-Liss, Inc。
Normal-appearing epithelium of cancer patients can harbor occult genetic abnormalities. Data comprehensively comparing gene expression between histologically normal breast epithelium of breast cancer patients and cancer-free controls are limited. The present study compares global gene expression between these groups. We performed microarrays using RNA from microdissected histologically normal terminal ductal-lobular units (TDLU) from 2 groups: (i) cancer normal (CN) (TDLUs adjacent to untreated ER+ breast cancers (n = 14)) and (ii) reduction mammoplasty (RM) (TDLUs of age-matched women without breast disease (n = 15)). Cyber-T identified differentially expressed genes. Quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC), and comparison to independent microarray data including 6 carcinomas in situ (CIS), validated the results. Gene ontology (GO), UniProt and published literature evaluated gene unction. About 127 probesets, corresponding to 1.05 genes, were differentially expressed between CN and RM (p < 0.0009, corresponding to FDR < 0.10). 104/127 (82%) probesets were also differentially expressed between CIS and RM, nearly always (102/104 (98%)) in the same direction as in CN vs. RM. Two-thirds of the 105 genes were implicated previously in carcinogenesis. Overrepresented functional groups included transcription, G-protein coupled and chemokine receptor activity, the MAPK cascade and immediate early genes. Most genes in these categories were under-expressed in CN vs. RM. We conclude that global gene expression abnormalities exist in normal epithelium of breast cancer patients and are also present in early cancers. Thus, cancer-related pathways may be perturbed in normal epithelium. These abnormalities could be markers of disease risk, occult disease, or the tissue's response to an existing tumor. (c) 2007 Wiley-Liss, Inc.