AUTHOR=Chen Dongjie , Huang Hui , Zang Longjun , Gao Wenzhe , Zhu Hongwei , Yu Xiao 

TITLE=Development and Verification of the Hypoxia- and Immune-Associated Prognostic Signature for Pancreatic Ductal Adenocarcinoma

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.728062

DOI=10.3389/fimmu.2021.728062

ISSN=1664-3224

ABSTRACT=We aim to construct a hypoxia- and immune-associated risk score model to predict the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). By unsupervised consensus clustering algorithms, we generate 2 different hypoxia clusters. Then we screened out 682 hypoxia-associated and 528 immune-associated PDAC DEGs differentially expressed genes (DEGs) of PDAC using Pearson correlation analysis based on the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression project (GTEx) dataset. 7 hypoxia and immune-associated signature genes (S100A16, PPP3CA, SEMA3C, PLAU, IL18, GDF11 and NR0B1) were identified to construct a risk score model using the Univariate Cox regression and the Least Absolute Shrinkage and Selection operator (LASSO) Cox regression, which stratified patients into high- and low-risk groups and were further validated in the GEO and ICGC cohort. Patients in low-risk group showed superior overall survival (OS) to their high-risk counterparts (p<0.05). Moreover, it was suggested by multivariate Cox regression that our constructed hypoxia-associated and immune-associated prognosis signature might be used as the independent factor for prognosis prediction (p<0.001). By CIBERSORT and ESTIMATE algorithms, we discovered that patients in high-risk groups had lower immune score, stromal score and immune checkpoint expression such as PD-L1, and different immunocyte infiltration states compared with those low-risk patients. The mutation spectrum also differs between high- and low-risk groups. To sum up, our hypoxia- and immune-associated prognostic signature can be used as an approach to stratify the risk of PDAC.