炎症相关因子可促进胃癌细胞的增殖，迁移和血管生成等，其中IL-8/CXCR2通路异常与胃癌相关。PADI4通过将蛋白的精氨酸催化为瓜氨酸，参与肿瘤病变，我们首次发现PADI4在胃癌组织和血清中高表达，可促进胃癌的发生，但致病机制不清。最近我们研究发现PADI4与IL-8/CXCR2之间存在相互调控作用，提示PADI4可能通过调控IL-8/CXCR2通路促进胃癌进展。本课题拟利用基因转染和抑制剂阻断等方法，明确1)PADI4对IL-8/CXCR2表达和功能的调控；2)PADI4对IL-8/CXCR2活性和亲和力的影响；3)炎性因子IL-8对PADI4的表达调控；4)PADI4、IL-8和CXCR2在胃癌组织中的表达相关性，探讨PADI4协同IL-8/CXCR2通路促进胃癌进展的分子机制，分析PADI4是否可作为“炎性调控因子”促进胃癌进展，为靶向PADI4抑制剂的临床治疗提供新的依据。

Inflammatory factors could promote gastric cancer cell proliferation, migration and angiogenesis, and the disregulation of IL-8/CXCR2 pathway is closely related with the occurrence and development of gastric cancer. Peptidylarginine deiminase 4 (PADI4) could promote tumor progression through post-translationally modifying arginine into citrulline. Our previous study found that PADI4 was highly expressed in the tissue and serum of gastric cancer and could promote the progression of gastric cancer. However, the underlying mechanism is still obscure. Recently, we found that 1) PADI4 could regulate the expression of CXCR2 and IL-8 protein; 2) PADI4 could be induced in the presence of inflammation factor IL-8, indicating that PADI4 may promote the progression of gastric cancer through regulating the IL-8/CXCR2 pathway. In this study, we applied of various techniques, such as gene transfection and inhibitor blocking in order to: (1) elucidate the regulation of PADI4 on the expression and function of IL-8 and CXCR2; (2) study the effect of PADI4 on the biology activity and affinity of IL-8/CXCR2; (3) characterize the expression PADI4 under inflammatory condition, such as IL-8;(4) characterize the clinico-pathological features of PADI4, IL-8 and CXCR2.The purpose of this study is to study the coordination between PADI4 and IL-8/CXCR2 pathway during tumor progression, and analyze whether PADI4 could be treated as a "inflammatory regulator factor" promote the progress of gastric cancer. This study may reveal a novel pathological mechanism regarding gastric cancer and provide credible evidence to treat gastric cancer with the inhibitor of PADI4.