These results demonstrate key roles for CagA and Cag T4SS activity in promoting gastric mucosal inflammation, transcriptional alterations, and proteomic alterations relevant to gastric carcinogenesis.<b>IMPORTANCE</b><i>Helicobacter pylori</i> colonizes the stomachs of about half of humans worldwide, and its presence is the primary risk factor for the development of stomach cancer. The gene discussed is S100A8; the disease is gastric cancer.