Improved survival among colon cancer patients with increased differentially expressed pathways

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• 作者：Martha L Slattery (1)
  Jennifer S Herrick (1)
  Lila E Mullany (1)
  Jason Gertz (2)
  Roger K Wolff (1)
  
  1. Department of Internal Medicine ; University of Utah School of Medicine ; 383 Colorow ; Salt Lake City ; 84018 ; USA
  2. Department of Oncological Sciences ; Huntsman Cancer Institute ; University of Utah School of Medicine ; 1950 Circle of Hope ; Salt Lake City ; 84112 ; USA
  
• 关键词：Colon cancer ; Gene expression ; MYC ; RNAseq ; TGFB1 ; TP53
• 刊名：BMC Medicine
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：13
• 期：1
• 全文大小：1,775 KB
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• 刊物主题：Medicine/Public Health, general; Biomedicine general;
• 出版者：BioMed Central
• ISSN：1741-7015

文摘

Background Studies of colorectal cancer (CRC) have shown that hundreds to thousands of genes are differentially expressed in tumors when compared to normal tissue samples. In this study, we evaluate how genes that are differentially expressed in colon versus normal tissue influence survival. Methods We performed RNA-seq on tumor/normal paired samples from 175 colon cancer patients. We implemented a cross validation strategy to determine genes that were significantly differentially expressed between tumor and normal samples. Differentially expressed genes were evaluated with Ingenuity Pathway Analysis to identify key pathways that were de-regulated. A summary differential pathway expression score (DPES) was developed to summarize hazard of dying while adjusting for age, American Joint Committee on Cancer (AJCC) stage, sex, and tumor molecular phenotype, i.e., MSI, TP53, KRAS, and CIMP. Results A total of 1,138 genes were up-regulated and 695 were down-regulated. These de-regulated genes were enriched for 19 Ingenuity Canonical Pathways, with the most significant pathways involving cell signaling and growth. Of the enriched pathways, 16 were significantly associated with CRC-specific mortality, including 1 metabolic pathway and 15 signaling pathways. In all instances, having a higher DPES (i.e., more de-regulated genes) was associated with better survival. Further assessment showed that individuals diagnosed at AJCC Stage 1 had more de-regulated genes than individuals diagnosed at AJCC Stage 4. Conclusions Our data suggest that having more de-regulated pathways is associated with a good prognosis and may be a reaction to key events that are disabling to tumor progression. Please see related article: http://dx.doi.org/10.1186/s12916-015-0307-6.