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Functional investigation shows TMIGD3 enrichment in angiogenesis, pancreas-beta cells, and TGF-beta signaling, with positive correlations to multiple immune-related scores. 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Comprehensive Investigation Illustrates the Role of M2 Macrophages and Its Related Genes in Pancreatic Cancer. Medicina 2023, 59, 717. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/medicina59040717](10.3390/medicina59040717)  \nAcademic Editor: Jincheng Wang  \nReceived: 20 December 2022  \nRevised: 27 March 2023  \nAccepted: 30 March 2023  \nPublished: 6 April 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nDepartment of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China  \n* [Correspondence: weng.shuqiang@zs-hospital.sh.cn](Correspondence: weng.shuqiang@zs-hospital.sh.cn) (S.W.); [dong.ling@zs-hospital.sh.cn](dong.ling@zs-hospital.sh.cn) (L.D.)† These authors contributed equally to this work.  \nAbstract: Background and Objectives: M2 macrophages play an important role in cancers. Our study aimed to illustrate the effect of M2 macrophages in pancreatic cancer (PC) . Materials and Methods: The open-access data used for analysis were downloaded from The Cancer Genome Atlas Program database, as well as some online databases. R software was mainly used for data analysis based on the speciﬁc packages. Results: Here, we comprehensively investigated the role of M2 macrophages and their related genes in PC. We performed the biological enrichment of M2 macrophages in PC. Meanwhile, we identiﬁed adenosine A3 receptor (TMIGD3) as the interest gene for further analysis. The single-cell analysis showed that was mainly expressed in the Mono/Macro cells based on the data from multiple data cohorts. Biological investigation showed that TMIGD3 was primarily enriched in angiogenesis, pancreas-beta cells and TGF-beta signaling. Tumor microenvironment analysis indicated that TMIGD3 was positively correlated with monocyte_MCPCOUNTER, NK cell_MCPCOUNTER, macrophages M2_CIBERSORT, macrophage_EPIC, neutrophil_TIMER and endothelial cell_MCPCOUNTER. Interestingly, we determined that all the immune functions quantiﬁed by single sample gene set enrichment analysis algorithms were activated in the patients with high TMIGD3 expression. Conclusions: Our results provide a novel direction for the research focused on the M2 macrophages in PC. Meanwhile, TMIGD3 was identiﬁed as an M2 macrophage-related biomarker for PC.  \nKeywords: pancreatic cancer; macrophages; TMIGD3; microenvironment; prognosis  \n1. Introduction  \nPancreatic cancer (PC), known as the “king of cancers”, is a highly malignant tumor of the digestive system, about 90% of which manifests in ductal adenocarcinomas with glandular epithelial origin [1] . Statistically, more than 490,000 new cases of PC are diagnosed each year worldwide [2] . Due to the highly insidious and aggressive biology of PC, most patients have no obvious symptoms in the early stage and are in the advanced stage once diagnosed [3] . Therefore, the prognosis for pancreatic cancer is poor, and despite current advances in chemotherapy, targeted therapy, and immunotherapy, the ﬁve-year survival rate for PC patients is less than 10%[4] . Therefore, it is still necessary to develop appropriate treatments to improve the survival rate of PC patients.  \nMacrophages, which are differentiated from monocytes in the blood after they penetrate the blood vessels, are a class of immune cells with phagocytic effects. Macrophages can be divided into two activation typ","cbCaiaqVasyWzWtZ","https://ap.wps.com/l/cbCaiaqVasyWzWtZ","pdf",9446098,13,"English","# Abstract\n# 1. Introduction\n# 2. Methods\n## 2.1. Acquisition and Pre-Processing of Open-Access Data","[{\"question\":\"What is the main research goal regarding M2 macrophages in pancreatic cancer?\",\"answer\":\"The study aims to illustrate the effect and role of M2 macrophages and related genes in pancreatic cancer. It focuses on identifying key genes linked to M2 macrophage activity.\"},{\"question\":\"How was TMIGD3 identified in this research?\",\"answer\":\"TMIGD3, an adenosine A3 receptor, was identified as an interest gene for further analysis. The study then examined its expression patterns using single-cell analysis and multiple data cohorts.\"},{\"question\":\"What biological and microenvironment findings connect TMIGD3 to pancreatic cancer?\",\"answer\":\"TMIGD3 was enriched in angiogenesis, pancreas-beta cells, and TGF-beta signaling. Tumor microenvironment analysis showed positive correlations between TMIGD3 and multiple immune-related cell and immune score metrics.\"}]","Comprehensive Investigation Illustrates the Role of M2 Macrophages and Its Related Genes in Pancreatic Cancer | PDF",1790227207,33]