The human genome encodes more than 50 interleukins (IL) and related proteins The majority of IL’S are synthesized by helper CD4 T lymphocytes, as well as through monocytes, macrophages, and endothelial cells. They promote the development and differentiation of T and B lymphocytes, and hematopoietic cells . Interleukin 1 alpha and interleukin 1 beta (IL1A and IL1B) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis . Similarly, few other important IL pathway genes like IL1R1, IL1R2, IL1RAP, IL1RN, and MYD88 have been found to be expressed highly in different solid tumors [1, 2, 3]. We hypothesize that these selected IL pathway genes can be used to predict the survival in different cancers.
Materials and Methods:
The microarray data of four different cancer types is analyzed in this study obtained from the Gene Expression Omnibus database (GEO). These specimens were used to establish cancer prognostic biomarker model and validation model. Associated clinical information like patient gender, clinical stage, neoplasm histologic grade, vital status, patient race, and patient’s days to death was also retrieved. The gene expression levels were measured for each cancer type with its respective reference as a control. Finally, Kaplan-Meier survival (KM) curve was applied to detect the differences of survival time for the index genes. Functions “Surv” and “survfit” were used for making survival objects and a survival fit . All the code repositories for analysis can be found on authors GitHub account at https://github.com/spawar2/Interleukin_Pathway_Survival_Gene_Expression_Analysis
All the patients selected in the study for lung, ovarian and head and neck cancer showed high expression of all the selected IL pathway genes. While 2, 1, 0, 58, 0, 51 and 15 pancreatic patients showed up-regulation of IL1A, IL1B, IL1R1, IL1R2, IL1RAP, IL1RN, and MYD88 genes. So we separated these patients as high expression cohort and remaining as low expression group patients. We further did a Kaplan-Meier survival (KM) curve comparing survival probability of patients with high and low six gene expression index in pancreatic cancer patients. Subsequent survival fits were plotted on same plot for ovarian, lung and head and neck cancer patients.
Conclusion and Discussion:
In our study, a cancer prognostic biomarker model constituted by few RNAs was established to stratify the risk hazards for these patients. Our results display a significant fold expression of all the IL pathway genes in ovarian, lung and head and neck cancers. The comparison of high and low expression of IL pathway genes in pancreatic patients reveal a difference but with an insignificant P-value. The reasons for which can be limitations in sample size, inter-sample variability etc.
Citation Format: shrikant pawar, Aditya Stanam. Predicting the prognosis for cancer patients with interleukins gene expression level [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 4247.