Bo Chen1, Chuan Hu2, Liqing Jiang3, Zhouxia Xiang1, Ziyi Zuo1, Yangjun Lin1, Chuan Liu4. 1. The First Clinical College, Wenzhou Medical University, Wenzhou, China. 2. Department of Joint Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China. 3. Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China. 4. Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China. Electronic address: lchuan6363@163.com.
Abstract
BACKGROUND: Immune-related genes (IRGs) are associated with the prognosis of different cancers and are helpful for the diagnosis and management of systematic treatment for cancer patients. However, there have been a few corresponding studies in pancreatic adenocarcinoma (PAAD). METHODS: The data of PAAD patients were obtained from the TCGA, GEO, and ICGC databases. Additionally, the expression profiles of the normal pancreas from the GTEx database were used to screen differentially expressed immune-related genes (DEIRGs). Cox regression analyses were used to explore overall survival (OS)- and progression-free survival (PFS)-related DEIRGs and to establish two nomograms for PAAD prognosis. Finally, transcription factor (TF), immune infiltration, and unsupervised consensus analyses were performed to understand the potential mechanisms. RESULTS: An OS-prognostic signature based on seven DEIRGs and a PFS-prognostic signature based on seven DEIRGs were generated, and their robust prognostic ability was confirmed by ROC curves (OS: 0.736 ~ 0.774, PFS: 0.732 ~ 0.840). According to the risk score, the OS and PFS of the high-risk group were poorer than those of the low-risk group in the training set and four external validation sets. In addition, two nomograms based on the signatures and clinical variables also showed excellent discrimination. And two hub regulatory pathways were successfully validated in several independent datasets. Discernable patterns of DEIRGs in unsupervised consensus analysis showed that patients with low expression of immune checkpoints had a favorable prognosis. CONCLUSION: Two DEIRG-based signatures can be used as independent tools for the prognostic prediction of PAAD and to provide potential novel immunotherapy targets.
BACKGROUND: Immune-related genes (IRGs) are associated with the prognosis of different cancers and are helpful for the diagnosis and management of systematic treatment for cancerpatients. However, there have been a few corresponding studies in pancreatic adenocarcinoma (PAAD). METHODS: The data of PAAD patients were obtained from the TCGA, GEO, and ICGC databases. Additionally, the expression profiles of the normal pancreas from the GTEx database were used to screen differentially expressed immune-related genes (DEIRGs). Cox regression analyses were used to explore overall survival (OS)- and progression-free survival (PFS)-related DEIRGs and to establish two nomograms for PAAD prognosis. Finally, transcription factor (TF), immune infiltration, and unsupervised consensus analyses were performed to understand the potential mechanisms. RESULTS: An OS-prognostic signature based on seven DEIRGs and a PFS-prognostic signature based on seven DEIRGs were generated, and their robust prognostic ability was confirmed by ROC curves (OS: 0.736 ~ 0.774, PFS: 0.732 ~ 0.840). According to the risk score, the OS and PFS of the high-risk group were poorer than those of the low-risk group in the training set and four external validation sets. In addition, two nomograms based on the signatures and clinical variables also showed excellent discrimination. And two hub regulatory pathways were successfully validated in several independent datasets. Discernable patterns of DEIRGs in unsupervised consensus analysis showed that patients with low expression of immune checkpoints had a favorable prognosis. CONCLUSION: Two DEIRG-based signatures can be used as independent tools for the prognostic prediction of PAAD and to provide potential novel immunotherapy targets.