Abstract 4922: Utility of evidence-based gene expression panels in predicting outcome in stage matched colorectal cancer patients
Authors: Bloomer Chance , Ahluwalia Pankaj , Pundkar Chetan , Heneidi Saleh , Jones Kimya , Mondal Ashis , Kolhe Ravindra 
Published: August 2019

Purpose: The aim of our study is to create an evidence-based gene expression analysis panel and use it to identify genes that can predict overall survival of stage matched colorectal cancer patients.

Procedure: We performed in silico analysis on 222 colorectal patients in TCGA using the nCounter PanCancer Human Progression Panel (genes n=742) on the cBioPortal platform. After extensive analysis of the individual genes and deep machine learning we selected 8 genes (NFKB1, ELK3, SEMA3E, ADRA2B, WNT5A, MMP14, PKM, and SDC4) associated with decreased survival (p&lt;.05) and 7 genes (VSIG4, SORD, CCR4, VEGFC, SETD2, RUNX1T1, and EPAS1) associated with increased survival (p&lt;.1) to include in our assay. Under an approved IRB protocol, we identified 750 colorectal cancer patients at the Georgia Cancer Center with a 5-year follow-up. The patients were divided into experimental groups based on tumor stage (AJCC stages 1-4), survival (+/-3 years), tumor grade (AJCC grades 1-3), and age(+/-76 years). RNA was isolated from FFPE blocks and analyzed by Nanostring’s custom 23-gene multiplex assay (15 experimental and 8 control). Statistical analyses included ANOVAs, Kaplan-Meier survival analysis, and subgroup analysis using Student’s t-test.

Results: The CCR4 gene, part of the increased survival panel, showed multiple significant associations with better prognosis. It had higher expression levels in patients with better survivals compared to those with worse survivals (p=.0119*). On survival analysis, higher expression was associated with increased survival (p=.004*). Subgroup analysis showed that patients with stage 4 cancer and better survivals had higher expression levels than those who had worse survivals and stage 4 (p=.0372*) or stage 1 (p=.0389*) tumors. The same trend was found when patients with stage 3 and better survivals were compared to patients with worse survivals and stage 4 (p=.0462*) or stage 1 (p=.0464*) tumors. Analysis of tumor grade plus survival and patient age plus survival gave more associations. Patients with grade 1 tumors and better survivals had higher expression levels than ones with low survival and either grade 1 (p=.0164*) or grade 2 tumors (p=.0026*). Young patients with better survivals had higher expression levels than those with worse survivals who were young (p=.0241*) or old (p=.0115*).

Discussion: These results show a significant correlation between high levels of CCR4 gene expression and longer survivals in patients with high stage tumors, a group rarely associated with such outcomes. The trend between the split survivals of stage 4 is interesting as a potential indicator of prognosis. Associations of age and grade could serve as prognostic indicators as well, especially the split survivals seen in grade 1 tumors and young patients. Future studies should include larger sample sizes as well as investigations into mechanistic explanations for these associations.

Citation Format: Chance Bloomer, Pankaj Ahluwalia, Chetan Pundkar, Saleh Heneidi, Kimya Jones, Ashis Mondal, Ravindra Kolhe. Utility of evidence-based gene expression panels in predicting outcome in stage matched colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4922.