Aging
Navigate
Submit an Article
Research Paper|Volume 12, Issue 22|pp 23217—23232

Alteration of tumor-associated macrophage subtypes mediated by KRT6A in pancreatic ductal adenocarcinoma

Junfeng Zhang1, Hui Sun2, Songsong Liu3, Wenjie Huang4, Jianyou Gu4, Zhiping Zhao3, Huan Qin3, Liwen Luo5, Jiali Yang1,3, Yongfei Fang2, Jiayun Ge6, Bing Ni7,8,9, Huaizhi Wang1
  • 1Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 401120, P R China
  • 2Department of Rheumatology, First Affiliated Hospital of Third Military Medical University, Chongqing 400038, P R China
  • 3Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, P R China
  • 4Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, P R China
  • 5Department of Orthopedics, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, P R China
  • 6Hepatopancreatobiliary Surgery Department, the Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, P R China
  • 7Department of Pathophysiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P R China
  • 8Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing 400038, P R China
  • 9Key Laboratory of High Altitude Medicine, PLA, Chongqing 400038, P R China
* Equal contribution
Received: December 21, 2019Accepted: September 3, 2020Published: November 18, 2020
https://doi.org/10.18632/aging.104091

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.