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直肠癌中DNA拷贝数改变的高分辨率分析:与转移、生存及mRNA表达的相关性

High-resolution analysis of DNA copy number alterations in rectal cancer: correlation with metastasis, survival, and mRNA expression.

作者信息

Doyen Jérôme, Letouzé Eric, Marisa Laetitia, de Reyniès Aurélien, Milano Gérard, Etienne-Grimaldi Marie-Christine, Olschwang Sylviane, Gaedcke Jochen, Ghadimi Michael, Gérard Jean-Pierre

机构信息

Department of Radiation Oncology, Centre Antoine-Lacassagne, 33 avenue de Valombrose, 06189, Nice, France,

出版信息

Strahlenther Onkol. 2014 Oct;190(11):1028-36. doi: 10.1007/s00066-014-0659-4. Epub 2014 Apr 26.

Abstract

BACKGROUND AND PURPOSE

This study aimed to determine the candidate genes and chromosomal imbalances capable of predicting occurrences of metastasis in patients with rectal cancer.

PATIENTS AND METHODS

Fresh frozen tumor tissues from 80 patients with rectal cancer were prospectively collected and analyzed using Affymetrix HG-U133 Plus 2.0 gene expression arrays and high-resolution Illumina single-nucleotide polymorphism (SNP) arrays. Endpoints of the study were metastasis-free survival (MFS) and cancer-specific survival (CSS).

RESULTS

The median follow-up was 102 months (1-146). Deletions of 8p and 1p36-35 correlated with worse MFS (p = 0.005 and p = 0.01, respectively) and CSS (p = 0.001 and p = 0.01, respectively). Multivariate analysis identified 8p deletion as an independent prognostic factor for MFS (p = 0.04) and CSS (p = 0.003); 97 genes located on the 8p chromosome were significantly underexpressed in tumors with 8p deletion.

CONCLUSION

This study shows for the first time in rectal cancer an independent correlation of 8p deletion with MFS and CSS and highlights potential new tumor suppressor genes.

摘要

背景与目的

本研究旨在确定能够预测直肠癌患者转移发生的候选基因和染色体失衡情况。

患者与方法

前瞻性收集80例直肠癌患者的新鲜冷冻肿瘤组织,并使用Affymetrix HG-U133 Plus 2.0基因表达阵列和高分辨率Illumina单核苷酸多态性(SNP)阵列进行分析。研究的终点为无转移生存期(MFS)和癌症特异性生存期(CSS)。

结果

中位随访时间为102个月(1 - 146个月)。8p和1p36 - 35的缺失与较差的MFS(分别为p = 0.005和p = 0.01)及CSS(分别为p = 0.001和p = 0.01)相关。多变量分析确定8p缺失是MFS(p = 0.04)和CSS(p = 0.003)的独立预后因素;位于8号染色体上的97个基因在8p缺失的肿瘤中显著低表达。

结论

本研究首次在直肠癌中显示8p缺失与MFS和CSS存在独立相关性,并突出了潜在的新肿瘤抑制基因。

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