Xiaoping Zuo,1,2,* Fuqiang Wang,1,* Guofeng Liu,3,* Shenglong Xie,1 Senyi Deng,1 Yun Wang1 

1Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Department of Thoracic Surgery, West China Guang’an Hospital, Sichuan University, Guang’an, People’s Republic of China; 3Department of Medical Administration, West China Guang’an Hospital, Sichuan University, Guang’an, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yun Wang, Department of Thoracic Surgery, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, People’s Republic of China, Email yunwwang@yeah.net

Background: This study investigates the prognostic value of M0 macrophage-related genes (M0MRGs) in esophageal cancer (ESCA) and identifies novel targets for immunotherapy.
Methods: Differentially expressed genes (DEGs) were screened with ESCA-related expression profile data (GSE5364 and GSE17351) from the GEO database, followed by GO and KEGG pathway enrichment analyses. Then, immune cell infiltration was examined with the CIBERSORT algorithm and multiplex fluorescence-based immunohistochemistry (MP-IHC). ESCA-related gene expression data and relevant clinical information were retrieved from TCGA. M0MRGs were identified with TCGA-ESCA based on Spearman’s correlation coefficient. Additionally, LASSO and Cox regression analyses were conducted to further construct an M0MRG-related prognostic model. ATP6V0D2 and MMP12 expression in ESCA was analyzed with tissue microarray. Finally, the half maximal inhibitory concentrations (IC50) of commonly used chemotherapeutics in TCGA-ESCA were calculated with the “oncoPredict” R package.
Conclusion: In summary, ATP6V0D2 and MMP12 were crucial components in a prognostic risk model for ESCA and were associated with poor prognoses, implicating the involvement of elevated M0 macrophages in disease progression and providing potential therapeutic targets and strategies for ESCA.

Keywords: esophageal cancer, M0 macrophage, prognostic model, ATP6V0D2, MMP12