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      Unraveling the potential of CD8, CD68, and VISTA as diagnostic and prognostic markers in patients with pancreatic ductal adenocarcinoma

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          Abstract

          Introduction

          Pancreatic cancer is a truculent disease with limited treatment options and a grim prognosis. Immunotherapy has shown promise in treating various types of cancer, but its effectiveness in pancreatic cancer has been lacking. As a result, it is crucial to identify markers associated with immunological pathways in order to improve the treatment outcomes for this deadly cancer. The purpose of this study was to investigate the diagnostic and prognostic significance of three markers, CD8, CD68, and VISTA, in pancreatic ductal adenocarcinoma (PDAC), the most common subtype of pancreatic cancer.

          Methods

          We analyzed gene expression data from Gene Expression Omnibus (GEO) database using bioinformatics tools. We also utilized the STRING online tool and Funrich software to study the protein-protein interactions and transcription factors associated with CD8, CD68, and VISTA. In addition, tissue microarray (TMA) and immunohistochemistry (IHC) staining were performed on 228 samples of PDAC tissue and 10 samples of normal pancreatic tissue to assess the expression levels of the markers. We then correlated these expression levels with the clinicopathological characteristics of the patients and evaluated their survival rates.

          Results

          The analysis of the GEO data revealed slightly elevated levels of VISTA in PDAC samples compared to normal tissues. However, there was a significant increase in CD68 expression and a notable reduction in CD8A expression in pancreatic cancer. Further investigation identified potential protein-protein interactions and transcription factors associated with these markers. The IHC staining of PDAC tissue samples showed an increased expression of VISTA, CD68, and CD8A in pancreatic cancer tissues. Moreover, we found correlations between the expression levels of these markers and certain clinicopathological features of the patients. Additionally, the survival analysis revealed that high expression of CD8 was associated with better disease-specific survival and progression-free survival in PDAC patients.

          Conclusion

          These findings highlight the potential of CD8, CD68, and VISTA as diagnostic and prognostic indicators in PDAC.

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          Most cited references103

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Cancer statistics, 2022

            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.
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              Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States.

              Cancer incidence and deaths in the United States were projected for the most common cancer types for the years 2020 and 2030 based on changing demographics and the average annual percentage changes in incidence and death rates. Breast, prostate, and lung cancers will remain the top cancer diagnoses throughout this time, but thyroid cancer will replace colorectal cancer as the fourth leading cancer diagnosis by 2030, and melanoma and uterine cancer will become the fifth and sixth most common cancers, respectively. Lung cancer is projected to remain the top cancer killer throughout this time period. However, pancreas and liver cancers are projected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related death by 2030, respectively. Advances in screening, prevention, and treatment can change cancer incidence and/or death rates, but it will require a concerted effort by the research and healthcare communities now to effect a substantial change for the future. ©2014 American Association for Cancer Research.
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                Author and article information

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                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                30 January 2024
                2024
                : 15
                : 1283364
                Affiliations
                [1] 1 Cellular and Molecular Research Center, Iran University of Medical Sciences , Tehran, Iran
                [2] 2 Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences , Tehran, Iran
                [3] 3 Department of Immunology, School of Medicine, Iran University of Medical Sciences , Tehran, Iran
                [4] 4 Oncopathology Research Center, Iran University of Medical Sciences , Tehran, Iran
                [5] 5 Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences , Tehran, Iran
                [6] 6 Human and Animal Cell Bank, Iranian Biological Resource Center (IBRC) , Tehran, Iran
                [7] 7 Immunology Board for Transplantation and Cell-Based Therapeutics (ImmunoTACT), Universal Scientific Education and Research Network (USERN) , Tehran, Iran
                [8] 8 Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences , Tehran, Iran
                [9] 9 Department of Pathology, School of Medicine, Iran University of Medical Sciences , Tehran, Iran
                [10] 10 Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences , Tehran, Iran
                [11] 11 Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences , Rafsanjan, Iran
                Author notes

                Edited by: Francesco Sabbatino, University of Salerno, Italy

                Reviewed by: Theodoros Michelakos, Harvard Medical School, United States

                Evangelos Koustas, National and Kapodistrian University of Athens, Greece

                †These authors have contributed equally to this work

                Article
                10.3389/fimmu.2024.1283364
                10865497
                38357542
                89c74775-f0f1-4ab8-90d0-f4e6c00424c6
                Copyright © 2024 Rezagholizadeh, Tajik, Talebi, Taha, Shariat Zadeh, Farhangnia, Hosseini, Nazari, Mollazadeh Ghomi, Kamrani Mousavi, Haeri Moghaddam, Khorramdelazad, Joghataei and Safari

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 August 2023
                : 15 January 2024
                Page count
                Figures: 9, Tables: 6, Equations: 0, References: 103, Pages: 21, Words: 9757
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by Iran University of Medical Sciences.
                Categories
                Immunology
                Original Research
                Custom metadata
                Cancer Immunity and Immunotherapy

                Immunology
                vista,pdac,cd68,pancreatic ductal adenocarcinoma,prognosis,biomarker,cd8
                Immunology
                vista, pdac, cd68, pancreatic ductal adenocarcinoma, prognosis, biomarker, cd8

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