Abstract 478: Investigating prognostic value of proinflammatory M1 gene expression in colorectal cancer patients
Authors: Pankaj Ahluwalia, Chance Bloomer, Chetan Pundkar, Kimya Jones, Ashis Mondal, Gagandeep Gahlay, Ravindra Kolhe
Journal: Cancer Research (2019)

Abstract Colorectal cancer (CRC) affects nearly 1.4 million individuals every year, making upto 10% of the global burden of cancer. Progress over the last few decades in surgical, chemotherapy and targeted therapy, have led to tremendous improvement in survival rate but the high risk of relapse and variable survival among the patients, calls for the need of better prognostic biomarkers. The tissue microenvironment and the presence of immune cells can be attributed to diverse immune response of individual patients that can lead to variable survival. Macrophage can showcase two polar phenotypes, M1 (inflammatory) and M2 (immunosuppressive). We set out to quantify the M1 oriented gene expression and its correlation with clinic-pathological characteristics of CRC patients. Under IRB approved protocol, a total of 750 CRC patients at Medical College of Georgia with 5 years follow-up were initially selected. The patients were stratified on the basis of overall survival in two groups, with higher (&amp;gt; 5 years) and lower survival (&amp;lt; 1 year) along with AJCC staging (I to IV), grade, gender and age. A total of 88 patients fitted in our inclusion criteria on the basis of survival duration after diagnosis. Total RNA was isolated and quantified through Nanodrop method. Next, the expression of immunological molecules which has the polarization immune potential were quantified through custom plexset using medium through-put Nanostring platform. We quantified expression of M1 macrophage immune gene signature using a custom 21 gene panel: - IRF5, STAT1, STAT6, CCL13, GATA3, CXCL9, CXCL10, CXCL11, IL15RA, IL15, IL1B, CEBPA, PPARG (along with 8 housekeeping genes). We used univariate and multivariate analysis to identify significant associations between gene expression and overall survival. In stage IV patients, STAT1 (p = 0.04*) and STAT6 (p = 0.03*) were expressed at higher levels. IL15RA (p = 0.01*) and IL1B (p = 0.01*) had higher expression in Stage III and IV patients compared to Stage I and II. Upon Kaplan-Meier Curves analysis, lower expression of CXCL9, 10, 11 correlated with poor prognosis with respect to overall survival (log-rank p = 0.038*, 0.009*, 0.034* respectively). In the multivariate analysis, using Cox-proportional hazard model, CCL13 (HR 3.18* p = 0.16*) and CEBPA (HR 14.4 p = 0.00*) were able to determine overall survival of the CRC patients. These initial findings highlight the clinical significance of transcriptome analysis in determining the prognosis for CRC patients. A comprehensive immune-based gene panel would assist in designing new therapies or can complement existing treatment regimes. Citation Format: Pankaj Ahluwalia, Chance Bloomer, Chetan Pundkar, Kimya Jones, Ashis Mondal, Gagandeep Gahlay, Ravindra Kolhe. Investigating prognostic value of proinflammatory M1 gene expression in 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 478.