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

被引:8
作者
Rezagholizadeh, Fereshteh [1 ,2 ,3 ]
Tajik, Fatemeh [4 ]
Talebi, Morteza [1 ,5 ,6 ]
Taha, Seyed Reza [4 ]
Zadeh, Mahdieh Shariat [4 ]
Farhangnia, Pooya [3 ,7 ,8 ]
Hosseini, Hamideh Sadat [1 ]
Nazari, Aram [1 ,9 ]
Ghomi, Shabnam Mollazadeh [1 ,7 ,9 ]
Mousavi, Seyede Mahtab Kamrani [1 ,10 ]
Moghaddam, Niloofar Haeri [1 ,10 ]
Khorramdelazad, Hossein [3 ,11 ]
Joghataei, Mohammad Taghi [1 ,2 ]
Safari, Elahe [3 ,8 ]
机构
[1] Iran Univ Med Sci, Cellular & Mol Res Ctr, Tehran, Iran
[2] Iran Univ Med Sci, Fac Adv Technol Med, Dept Mol Med, Tehran, Iran
[3] Iran Univ Med Sci, Sch Med, Dept Immunol, Tehran, Iran
[4] Iran Univ Med Sci, Oncopathol Res Ctr, Tehran, Iran
[5] Iran Univ Med Sci, Fac Med, Dept Med Genet & Mol Biol, Tehran, Iran
[6] Iranian Biol Resource Ctr IBRC, Human & Anim Cell Bank, Tehran, Iran
[7] Universal Sci Educ & Res Network USERN, Immunol Board Transplantat & Cell Based Therapeut, Tehran, Iran
[8] Iran Univ Med Sci, Inst Immunol & Infect Dis, Immunol Res Ctr, Tehran, Iran
[9] Iran Univ Med Sci, Sch Med, Dept Pathol, Tehran, Iran
[10] Iran Univ Med Sci, Fac Adv Technol Med, Dept Med Nanotechnol, Tehran, Iran
[11] Rafsanjan Univ Med Sci, Sch Med, Dept Immunol, Rafsanjan, Iran
关键词
VISTA; PDAC; CD68; pancreatic ductal adenocarcinoma; prognosis; biomarker; CD8; IMMUNE-CHECKPOINT; POOR-PROGNOSIS; T-CELLS; EXPRESSION; CTLA-4;
D O I
10.3389/fimmu.2024.1283364
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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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页数:21
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共 103 条
[1]   Pancreatic cancer: yesterday, today and tomorrow [J].
Ansari, Daniel ;
Tingstedt, Bobby ;
Andersson, Bodil ;
Holmquist, Fredrik ;
Sturesson, Christian ;
Williamsson, Caroline ;
Sasor, Agata ;
Borg, David ;
Bauden, Monika ;
Andersson, Roland .
FUTURE ONCOLOGY, 2016, 12 (16) :1929-1946
[2]  
Badawi Manal A, 2015, Open Access Maced J Med Sci, V3, P209, DOI 10.3889/oamjms.2015.044
[3]   Immune Cytolytic Activity Stratifies Molecular Subsets of Human Pancreatic Cancer [J].
Balli, David ;
Rech, Andrew J. ;
Stanger, Ben Z. ;
Vonderheide, Robert H. .
CLINICAL CANCER RESEARCH, 2017, 23 (12) :3129-3138
[4]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[5]   Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer [J].
Blando, Jorge ;
Sharma, Anu ;
Higa, Maria Gisela ;
Zhao, Hao ;
Vence, Luis ;
Yadav, Shalini S. ;
Kim, Jiseong ;
Sepulveda, Alejandro M. ;
Sharp, Michael ;
Maitra, Anirban ;
Wargo, Jennifer ;
Tetzlaff, Michael ;
Broaddus, Russell ;
Katz, Matthew H. G. ;
Varadhachary, Gauri R. ;
Overman, Michael ;
Wang, Huamin ;
Yee, Cassian ;
Bernatchez, Chantale ;
Iacobuzio-Donahue, Christine ;
Basu, Sreyashi ;
Allison, James P. ;
Sharma, Padmanee .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (05) :1692-1697
[6]   The novel negative checkpoint regulator VISTA is expressed in gastric carcinoma and associated with PD-L1/PD-1: A future perspective for a combined gastric cancer therapy? [J].
Boeger, Christine ;
Behrens, Hans-Michael ;
Krueger, Sandra ;
Roecken, Christoph .
ONCOIMMUNOLOGY, 2017, 6 (04)
[7]   Prognostic Significance of CD4+and CD8+Tumor-Infiltrating Lymphocytes in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis [J].
Borsetto, Daniele ;
Tomasoni, Michele ;
Payne, Karl ;
Polesel, Jerry ;
Deganello, Alberto ;
Bossi, Paolo ;
Tysome, James R. ;
Masterson, Liam ;
Tirelli, Giancarlo ;
Tofanelli, Margherita ;
Boscolo-Rizzo, Paolo .
CANCERS, 2021, 13 (04) :1-15
[8]   Macrophage Polarization States in the Tumor Microenvironment [J].
Boutilier, Ava J. ;
Elsawa, Sherine F. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (13)
[9]   Defining the Signature of VISTA on Myeloid Cell Chemokine Responsiveness [J].
Broughton, Thomas W. K. ;
ElTanbouly, Mohamed A. ;
Schaafsma, Evelien ;
Deng, Jie ;
Sarde, Aurelien ;
Croteau, Walburga ;
Li, Jiannan ;
Nowak, Elizabeth C. ;
Mabaera, Rodwell ;
Smits, Nicole C. ;
Kuta, Anna ;
Noelle, Randolph J. ;
Lines, J. Louise .
FRONTIERS IN IMMUNOLOGY, 2019, 10
[10]   VISTA Expression on Immune Cells Correlates With Favorable Prognosis in Patients With Triple-Negative Breast Cancer [J].
Cao, Xi ;
Ren, Xinyu ;
Zhou, Yidong ;
Mao, Feng ;
Lin, Yan ;
Wu, Huanwen ;
Sun, Qiang .
FRONTIERS IN ONCOLOGY, 2021, 10