Research Paper Volume 12, Issue 22 pp 23217—23232
Alteration of tumor-associated macrophage subtypes mediated by KRT6A in pancreatic ductal adenocarcinoma
- 1 Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 401120, P R China
- 2 Department of Rheumatology, First Affiliated Hospital of Third Military Medical University, Chongqing 400038, P R China
- 3 Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, P R China
- 4 Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, P R China
- 5 Department of Orthopedics, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, P R China
- 6 Hepatopancreatobiliary Surgery Department, the Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, P R China
- 7 Department of Pathophysiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P R China
- 8 Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing 400038, P R China
- 9 Key Laboratory of High Altitude Medicine, PLA, Chongqing 400038, P R China
Received: December 21, 2019 Accepted: September 3, 2020 Published: November 18, 2020
https://doi.org/10.18632/aging.104091How to Cite
Copyright: © 2020 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is severely affecting the health and lives of patients. Clarifying the composition and regulatory factors of tumor immune microenvironment (TIME) is helpful for the treatment of PDAC. We analyzed the unique TIMEs and gene expression patterns between PDAC and adjacent normal tissue (ANT) using Gene Expression Omnibus (GEO) to find new immunotherapy targets. The Cancer Genome Atlas (TCGA) datasets were used to elucidate the possible mechanism of which tumor-associated macrophages (TAMs) changed in PDAC. We found that the composition of TAMs subtypes, including M0, M1, and M2, was different between PDAC and ANT, which was validated in recently published single-cell RNA-seq data. Many immune cells interacted with each other to affect the TIME. There were many DEGs enriched in some pathways that could potentially change the immune cell composition. KRT6A was found to be a DEG between PDAC and ANT that overlapped with DEGs between the M0-high group and the M0-low group in TCGA datasets, and it might alter and regulate TAMs via a collection of genes including COL5A2, COL1A2, MIR3606, SPARC, and COL6A3. TAMs, which could be a target of immunotherapy, might be influenced by genes through KRT6A and indicate an undesirable prognosis in PDAC.
Abbreviations
PDAC: pancreatic ductal adenocarcinoma; GSEA: Gene set enrichment analysis; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; TIME: tumor immune microenvironment; TAMs: tumor-associated macrophages; ANT: adjacent normal tissue; DEGs: differentially expressed genes; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; STEM: Short Time-series Expression Miner; PPI: Protein-protein interaction.