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晚期人类宫颈癌中的基因表达模式。

Gene expression patterns in advanced human cervical cancer.

作者信息

Grigsby P W, Watson M, Powell M A, Zhang Z, Rader J S

机构信息

Department of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA.

出版信息

Int J Gynecol Cancer. 2006 Mar-Apr;16(2):562-7. doi: 10.1111/j.1525-1438.2006.00389.x.

Abstract

The purpose of this study was to evaluate gene expression patterns in human cervical tumors by extent of lymph node metastases at diagnosis. Pretreatment whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging was performed in eight patients with invasive squamous cell carcinoma of the cervix to evaluate the extent of lymph nodes metastases. Pretreatment tumor tissue samples were subjected to laser-capture microdissection, and isolated RNA was linearly amplified and hybridized to Affymetrix Human U95A GeneChip microarrays. Molecular FDG-PET imaging revealed that three patients had lymph node involvement in the supraclavicular region and five patients did not. Microarray data were segregated into two groups based on the extent of regional lymph node involvement. Supervised clustering analysis identified 75 of about 12,000 gene transcripts represented on the array whose average expression was at least threefold different. We identified 12 of the 75 transcripts that demonstrated a statistically significant difference in expression between the two patient groups (P < 0.05). Five transcripts were upregulated and seven downregulated. Both overall and cause-specific survivals were different between these two patient groups (P= 0.006). This limited data set identified candidate biomarkers of extent of lymph node metastases that correlated with poor survival outcome.

摘要

本研究的目的是根据诊断时淋巴结转移程度评估人类宫颈肿瘤中的基因表达模式。对8例宫颈浸润性鳞状细胞癌患者进行了治疗前全身氟脱氧葡萄糖-正电子发射断层扫描(FDG-PET)成像,以评估淋巴结转移程度。对治疗前肿瘤组织样本进行激光捕获显微切割,分离出的RNA进行线性扩增,并与Affymetrix Human U95A基因芯片微阵列杂交。分子FDG-PET成像显示,3例患者锁骨上区域有淋巴结受累,5例患者没有。根据区域淋巴结受累程度将微阵列数据分为两组。监督聚类分析在阵列上约12000个基因转录本中鉴定出75个,其平均表达至少相差三倍。我们在75个转录本中鉴定出12个,在两组患者之间其表达存在统计学显著差异(P < 0.05)。5个转录本上调,7个下调。这两组患者的总生存率和病因特异性生存率均不同(P = 0.006)。这个有限的数据集确定了与不良生存结果相关的淋巴结转移程度的候选生物标志物。

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