AUTHOR=Su Yang , Qi Ruoshan , Li Lanying , Wang Xu , Li Sijin , Zhao Xuan , Hou Rui , Ma Wen , Liu Dan , Zheng Junnian , Shi Ming 

TITLE=An immune-related gene prognostic risk index for pancreatic adenocarcinoma

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.945878

DOI=10.3389/fimmu.2022.945878

ISSN=1664-3224

ABSTRACT=<sec><title>Objective</title><p>Our goal is to construct an immune-related gene prognostic risk index (IRGPRI) for pancreatic adenocarcinoma (PAAD), and to clarify the immune and molecular features in IRGPRI-defined PAAD subgroups and the benefit of immune checkpoint inhibitors (ICIs) therapy.</p></sec><sec><title>Method</title><p>Through differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and univariate Cox regression analysis, 16 immune-related hub genes were identified using the Cancer Genome Atlas (TCGA) PAAD dataset (n = 182) and immune gene set. From these genes, we constructed an IRGPRI with the Cox regression method and the IRGPRI was verified based on the Gene Expression Omnibus (GEO) dataset (n = 45). Then, we analyzed the immune and molecular features and the benefit of ICI therapy in IRGPRI-defined subgroups.</p></sec><sec><title>Results</title><p>Five genes, including <italic>S100A16</italic>, <italic>CD40</italic>, <italic>VCAM1</italic>, <italic>TNFRSF4</italic> and <italic>TRAF1</italic> were used to construct IRGPRI. As with the results of the GEO cohort, the overall survival (OS) was more favorable in low IRGPRI patients versus high IRGPRI patients. The composite results pointed out that low IRGPRI was associated with immune response-related pathways, high level of CTLA4, low KRAS and TP53 mutation rate, more infiltration of activated memory CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, and more benefits from ICIs therapy. In comparison, high IRGPRI was associated with cancer-related pathways, low expression of CTLA4, high KRAS and TP53 mutation rate, more infiltration of M2 macrophages, and less benefit from ICIs therapies.</p></sec><sec><title>Conclusion</title><p>This IRGPRI is an encouraging biomarker to define the prognosis, immune and molecular features, and benefits from ICIs treatments in PAAD.</p></sec>