Abstract LB-213: Pro-angiogenic and myeloid cell gene expression markers in prognostication of advanced stage colorectal cancer patients

Abstract

Abstract Colorectal cancer (CRC) is third deadliest cancer in United States, only behind lung and prostate cancer. Myeloid cell involvement in tumor development is dichotomous. There is evidence that they can be immunostimulatory and tumor suppressive as well as immunosuppressive and tumorigenic. These cells seem to play a crucial role in tumor angiogenesis & vasculogenesis. The functional fluidity is driven by factors present in the tumor microenvironment (TME), which alter myeloid cell gene expression and thus phenotype & function. Broadly, the pathologic myeloid cells present within the tumor can be broken down into two classes: immature myeloid-derived suppressor cells (MDSCs) & mature tumor-associated myeloid cells (TAMCs). This project investigates the angiogenic/vasculogenic gene signatures of MDSCs & TAMCs. Seven genes that were either markers of myeloid cells or expressed by pro-angiogenic MDSCs & TAMCs: CD14, CD15, VEGF, TNF-a, TGF-b, cathepsin B, & MMP-14 were analyzed in tumor samples using Syber Green qPCR. The aim of this study is to determine possible associations of gene expression with endpoints such as tumor stage, tumor grade & patient survival, so as to determine their prognostic value in predicting outcome in CRC patients. Under the IRB approved protocol, a total of 750 colon cancer 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 (> 5 years) and lower survival (<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. H&E slides were reviwed and macrodissected for tumor only regions. Total RNA was isolated and quantified through Nanodrop method. The statistical analysis of data was performed using student t-test. Compared to stage 1 patients, CD15 expression was found to be significantly upregulated in stage 4 (p=0.04). The same observation was made for stage 2 (p=0.06) and 3 patients (0.54), though it did not achieve statistical significance (p=0.076). Also, TGF-b expression was found to be significantly upregulated in stage 2 (p=0.05) & stage 4 (p=0.05). The same observation was made for stage 3 patients, though it did not achieve statistical significance (p=0.076). Our findings suggest that both CD15 (marker of mature myeloid cell populations), and TGF-β (associated with both immunosuppresion and angiogenesis) are associated with advanced stage colorectal cancer. CD15 and TGF-β seems to be potential biomarkers of prognostic significance. Inaddition, TGF-B might be targeted in advanced colorectal cancer for personalized therapy. Citation Format: Ben Johnson, Nikhil Sahajpal, Pankaj Ahaluwalia, Ashis Mondal, Allan Njau, Meenaskhi Ahaluwalia, Ravindra Kolhe. Pro-angiogenic and myeloid cell gene expression markers in prognostication of advanced stage colorectal cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-213.