Improved survival among colon cancer patients with increased differentially expressed pathways

BMC Medicine

Roger K Wolff²  Jason Gertz¹  Lila E Mullany²  Jennifer S Herrick²  Martha L Slattery² 

[1]Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, 1950 Circle of Hope, Salt Lake City 84112, USA

[2]Department of Internal Medicine, University of Utah School of Medicine, 383 Colorow, Salt Lake City 84018, USA

关键词: TP53;    TGFB1;    RNAseq;    MYC;    Gene expression;    Colon cancer;   

Others  :  1160628
DOI  :  10.1186/s12916-015-0292-9

 received in 2015-01-05, accepted in 2015-02-11,  发布年份 2015

【 摘 要 】

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 webcite.

【 授权许可】

   
2015 Slattery et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

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