Transcriptional profiling reveals H.pylori-assocaited genes induced inflammatory cell infiltration and chemoresistance in gastric cancer

Xuehui Hong^1,2*Jinshui Tan²Zhengxin Wu³Yuankun Liu⁴Wei Wang²Wenjuan Qin⁵Guangchao Pan²Yubo Xiong²Jingsong Ma²Jiabao Zhao²Huiwen Zhou²Zhengjin Liu⁶Cen Huang⁷Daxun Piao⁷Haijie Lu⁵Huiqin Zhuo²

• ¹Xiamen University, Xiamen, China
• ²Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, China
• ³Department of Radiology, First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Jiangsu Province, China
• ⁴Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, China
• ⁵Department of Radiation Oncology, Zhongshan Hospital Affiliated, School of Medicine, Xiamen University, Xiamen, China, Xiamen, China
• ⁶Department of Pathology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
• ⁷Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China

Background: H. pylori infection is closely associated with the tumor microenvironment (TME) in gastric cancer (GC), yet its underlying mechanism is elusive. Hence, it is imperative to explore the microenvironment and drug resistance arising from H. pylori to enhance therapeutic strategies for GC.Methods: Employing transcriptional bioinformatics, we computed a H. pyloriassociated prognostic index (HPI) using datasets from TCGA and GSE62254 containing ACSM5 and HSPB2 gene expression. We assessed IC50 values for anticancer drugs and immune cell infiltration to evaluate the therapeutics and TME based on the HPI. Further, we validated the transcriptional profiling findings by examining drug sensitivity transfected with siACSM5 and siHSPB2 and analyzing scRNA-seq data and clinical patient samples.Results: ACSM5 and HSPB2 were identified as correlates of H. pylori infection in GC.Significantly, we established the H. pylori-associated prognostic index (HPI) and found that a high HPI was linked with a worse prognosis. Classification based on the HPI indicated an enhanced infiltration of tumor microenvironment cells and resistance to anti-tumor drugs.The HPI, reflecting newly identified and complementary biomarkers, correlated with the TME and could accurately project chemoresistance and an altered immune cell distribution in GC patients, thus providing clinical guidance on therapeutic interventions.