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J Proteome Res. 2016 Mar 4;15(3):766-76. doi: 10.1021/acs.jproteome.5b00847. Epub 2015 Dec 29.

Integrative Omics Analysis Reveals Post-Transcriptionally Enhanced Protective Host Response in Colorectal Cancers with Microsatellite Instability.

Liu Q1,2, Zhang B1,2,3,4.

Author information

1
Department of Biomedical Informatics, Vanderbilt University School of Medicine , Nashville, Tennessee 37232, United States.
2
Center for Quantitative Sciences, Vanderbilt University School of Medicine , Nashville, Tennessee 37232, United States.
3
Department of Cancer Biology, Vanderbilt University School of Medicine , Nashville, Tennessee 37232, United States.
4
Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine , Nashville, Tennessee 37232, United States.

Abstract

Microsatellite instability (MSI) is a frequent and clinically relevant molecular phenotype in colorectal cancer. MSI cancers have favorable survival compared with microsatellite stable cancers (MSS), possibly due to the pronounced tumor-infiltrating lymphocytes observed in MSI cancers. Consistent with the strong immune response that MSI cancers trigger in the host, previous transcriptome expression studies have identified mRNA signatures characteristic of immune response in MSI cancers. However, proteomics features of MSI cancers and the extent to which the mRNA signatures are reflected at the protein level remain largely unknown. Here, we performed a comprehensive comparison of global proteomics profiles between MSI and MSS colorectal cancers in The Cancer Genome Atlas (TCGA) cohort. We found that protein signatures of MSI are also associated with increased immunogenicity. To reliably quantify post-transcription regulation in MSI cancers, we developed a resampling-based regression method by integrative modeling of transcriptomics and proteomics data sets. Compared with the popular simple method, which detects post-transcriptional regulation by either identifying genes differentially expressed at the mRNA level but not at the protein level or vice versa, our method provided a quantitative, more sensitive, and accurate way to identify genes subject to differential post-transcriptional regulation. With this method, we demonstrated that post-transcriptional regulation, coordinating protein expression with key players, initiates de novo and enhances protective host response in MSI cancers.

KEYWORDS:

colorectal cancer; integrative omics analysis; microsatellite instability; post-transcription regulation; protective host response

PMID:
26680540
PMCID:
PMC4782175
DOI:
10.1021/acs.jproteome.5b00847
[Indexed for MEDLINE]
Free PMC Article

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