Reduced expression of a gene proliferation signature is associated with enhanced malignancy in colon cancer.
Reduced expression of a gene proliferation signature is associated with enhanced malignancy in colon cancer.
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DOI：
10.1038/sj.bjc.6604560
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发表时间：
2008-09-16
影响因子：
8.8
通讯作者：
Reeve, A. E.
中科院分区：
文献类型：
--
作者：
Anjomshoaa, A.;Lin, Y-H;Black, M. A.;McCall, J. L.;Humar, B.;Song, S.;Fukuzawa, R.;Yoon, H. -S;Holzmann, B.;Friederichs, J.;Van Rij, A.;Thompson-Fawcett, M.;Reeve, A. E.
细胞增殖和结肠癌恶性潜能之间的关系还不清楚。在这里，我们使用结肠特异性基因增殖签名（GPS）评估了这种关联。GPS是通过结合从癌细胞系模型和已发表的结肠隐窝概况的分析中获得的基因表达数据而得到的。GPS在体外活跃的周期细胞和结肠隐窝的增殖区室中均过表达。使用K均值聚类将两组结肠肿瘤独立地分层为具有高和低GPS表达的两组。值得注意的是，我们观察到GPS表达减少与复发可能性增加之间存在显著相关性（P<0.05），导致两个队列的无病生存期缩短。这一发现不是方法学偏倚的结果，因为我们通过将我们的GPS应用于公开的乳腺癌数据，验证了乳腺癌恶性程度和增殖增加之间的既定关联。在这项研究中，我们表明，增殖减少是大多数侵袭性结肠癌的生物学特征。这与许多其他癌症如乳腺癌形成对比。调查这种不寻常的观察结果背后的原因可能会提供重要的洞察结肠癌进展的生物学和推定的新的治疗方案。
The association between cell proliferation and the malignant potential of colon cancer is not well understood. Here, we evaluated this association using a colon-specific gene proliferation signature (GPS). The GPS was derived by combining gene expression data obtained from the analysis of a cancer cell line model and a published colon crypt profile. The GPS was overexpressed in both actively cycling cells in vitro and the proliferate compartment of colon crypts. K-means clustering was used to independantly stratify two cohorts of colon tumours into two groups with high and low GPS expression. Notably, we observed a significant association between reduced GPS expression and an increased likelihood of recurrence (P<0.05), leading to shorter disease-free survival in both cohorts. This finding was not a result of methodological bias as we verified the well-established association between breast cancer malignancy and increased proliferation, by applying our GPS to public breast cancer data. In this study, we show that reduced proliferation is a biological feature characterizing the majority of aggressive colon cancers. This contrasts with many other carcinomas such as breast cancer. Investigating the reasons underlying this unusual observation may provide important insight into the biology of colon cancer progression and putative novel therapy options.
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影响因子：
45.3
作者：
Garrity, MM;Burgart, LJ;Witzig, TE
通讯作者：
Witzig, TE
DOI：
10.1073/pnas.96.16.9212
发表时间：
1999-08-03
影响因子：
11.1
作者：
Perou, CM;Jeffrey, SS;Botstein, D
通讯作者：
Botstein, D
DOI：
10.1073/pnas.091062498
发表时间：
2001-04-24
影响因子：
11.1
作者：
Tusher, VG;Tibshirani, R;Chu, G
通讯作者：
Chu, G
影响因子：
3.3
作者：
Chen, X;Cheung, ST;Brown, PO
通讯作者：
Brown, PO
影响因子：
8
作者：
Inamura, K;Fujiwara, T;Ishikawa, Y
通讯作者：
Ishikawa, Y