The nine ADAMs family members serve as potential biomarkers for immune infiltration in pancreatic adenocarcinoma

Author:

Qi Bing1,Liu Han2,Dong Ying3,Shi Xueying4,Zhou Qi4,Zeng Fen4,Bao Nabuqi4,Li Qian4,Yuan Yuan5,Yao Lei6,Xia Shilin7

Affiliation:

1. Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China

2. College of Stomatology, Dalian Medical University, Dalian, China

3. Gastrointestinal Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, China

4. Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China

5. Clinical Nutrition Department, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China

6. Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China

7. Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China

Abstract

Background The functional significance of ADAMs family members in the immune infiltration of pancreatic adenocarcinoma (PAAD) awaits elucidation. Methods ADAMs family members with significant expression were identified among differentially expressed genes of PAAD based on The Cancer Genome Atlas (TCGA) database followed by a verification based on the Oncomine database. The correlation of ADAMs in PAAD was estimated with the Spearman’s rho value. The pathway enrichment of ADAMs was performed by STRING and GSEALite, respectively. The protein–protein interaction and Gene Ontology analyses of ADAMs and their similar genes were exanimated in STRING and visualized by Cytoscape. Subsequently, the Box-Whisker plot was used to show a correlation between ADAMs and different tumor grade 1/2/3/4 with Student’s t-test. TIMER was applied to estimate a correlation of ADAMs expressions with immune infiltrates and immune checkpoint blockade (ICB) immunotherapy-related molecules. Furthermore, the effect of copy number variation (CNV) of ADAMs genes was assessed on the immune infiltration levels. Result ADAM8/9/10/12/15/19/28/TS2/TS12 were over-expressed in PAAD. Most of the nine ADAMs had a significant correlation. ADAM8/12/15/19 expression was remarkably increased in the comparison between grade 1 and grade 2/3 of PAAD. ADAM8/9/10/12/19/28/TS2/TS12 had a positive correlation with almost five immune infiltrates. ADAM12/19/TS2/TS12 dramatically related with ICB immunotherapy-related molecules. CNV of ADAMs genes potentially influenced the immune infiltration levels. Conclusion Knowledge of the expression level of the ADAMs family could provide a reasonable strategy for improved immunotherapies to PAAD.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Liaoning Province

Scientific Research Fund of Liaoning Provincial Education Department

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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