Abstract
Abstract It has long been observed that cancer development tends to be associated with chronic inflammation. Recent epidemiology studies have suggested chronic inflammation may be causally linked to a larger number of sporadic cancers. In this work, we have conducted a Pan-inflammatory and precancerous diseases analysis by comparing the 173 transcriptomics data sets consisting 4073 disease and 2669 normal human tissue samples of 10 cancer prone and 8 cancer independent inflammatory diseases, 11 precancerous diseases or benign tumors and 20 cancer types, aiming to identify fundamental differences between cancer-prone chronic inflammations and cancer-independent chronic inflammations and what biological characteristics cause cancer initiation or increased oncogenic risk. By applying differential gene expression, co-expression network, our in-house immune cell deconvolution and machine learning based hypoxia/oxidative stress prediction methods on the collected data, we have discovered the cancer prone chronic inflammatory diseases consistently have: (1) elevated relative proportion of CD4+ T, Macrophage, and Neutrophil cells, (2) decreased CD8 + T, adipocyte, monocyte and B cells, (3) highly disorder tissue repair phase I - IV related pathways, (4) increased oxidative stress level associated with Macrophage and Neutrophil proportions, (5) elevated iron ion metabolism, (6) over expressed extracellular glycosaminoglycan metabolism and (6) suppressed mitochondrial activity. These analyses results strongly suggest that there is a necessary pathway for the majority or all chronic inflammatory diseases to become cancerous, namely consecutively dysregulated tissue repair process, increased reactive oxygen species producing immune cells, damage of extracellular matrix, Fenton reaction and production of hydroxyl radical and dysregulated mitochondrial activity. We believe these new insights could provide highly useful information in guiding future studies of inflammation associated cancers. Citation Format: Chi Zhang, Fang Yao, Sha Cao, Tao Sheng, Sen Liang, Wei Du, Ying Xu. A pan-inflammatory and precancerous disease analysis reveals key biological characteristics in chronic inflammatory diseases with high oncogenic risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 560. doi:10.1158/1538-7445.AM2017-560
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