title: Genome-wide multi-omics profiling of colorectal cancer identifies immune determinants strongly associated with relapse.
abstract: The use and benefit of adjuvant chemotherapy to treat stage II colorectal cancer (CRC) patients is not well understood since the majority of these patients are cured by surgery alone. Identification of biological markers of relapse is a critical challenge to effectively target treatments to the ~20% of patients destined to relapse. We have integrated molecular profiling results of several "omics" data types to determine the most reliable prognostic biomarkers for relapse in CRC using data from 40 stage I and II CRC patients. We identified 31 multi-omics features that highly correlate with relapse. The data types were integrated using multi-step analytical approach with consecutive elimination of redundant molecular features. For each data type a systems biology analysis was performed to identify pathways biological processes and disease categories most affected in relapse. The biomarkers detected in tumors urine and blood of patients indicated a strong association with immune processes including aberrant regulation of T-cell and B-cell activation that could lead to overall differences in lymphocyte recruitment for tumor infiltration and markers indicating likelihood of future relapse. The immune response was the biologically most coherent signature that emerged from our analyses among several other biological processes and corroborates other studies showing a strong immune response in patients less likely to relapse.
authors: Department of Oncology, Innovation Center for Biomedical Informatics, Georgetown University Medical Center Washington, DC, USA ; Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center Washington DC, USA.
authors: Subha
authors: S
authors: Madhavan
authors: Yuriy
authors: Y
authors: Gusev
authors: Thanemozhi G
authors: TG
authors: Natarajan
authors: Lei
authors: L
authors: Song
authors: Krithika
authors: K
authors: Bhuvaneshwar
authors: Robinder
authors: R
authors: Gauba
authors: Abhishek
authors: A
authors: Pandey
authors: Bassem R
authors: BR
authors: Haddad
authors: David
authors: D
authors: Goerlitz
authors: Amrita K
authors: AK
authors: Cheema
authors: Hartmut
authors: H
authors: Juhl
authors: Bhaskar
authors: B
authors: Kallakury
authors: John L
authors: JL
authors: Marshall
authors: Stephen W
authors: SW
authors: Byers
authors: Louis M
authors: LM
authors: Weiner
keywords: colorectal cancer; exome sequencing; immune response; integrative analysis; multi-omics; relapse; systems biology; variant analysis