解析CD8、CD68和VISTA作为胰腺导管腺癌患者诊断和预后标志物的潜力。
Unraveling the potential of CD8, CD68, and VISTA as diagnostic and prognostic markers in patients with pancreatic ductal adenocarcinoma.
作者信息
Rezagholizadeh Fereshteh, Tajik Fatemeh, Talebi Morteza, Taha Seyed Reza, Shariat Zadeh Mahdieh, Farhangnia Pooya, Hosseini Hamideh Sadat, Nazari Aram, Mollazadeh Ghomi Shabnam, Kamrani Mousavi Seyede Mahtab, Haeri Moghaddam Niloofar, Khorramdelazad Hossein, Joghataei Mohammad Taghi, Safari Elahe
机构信息
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
出版信息
Front Immunol. 2024 Jan 30;15:1283364. doi: 10.3389/fimmu.2024.1283364. eCollection 2024.
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.
引言
胰腺癌是一种恶性疾病，治疗选择有限，预后严峻。免疫疗法在治疗各类癌症方面已显示出前景，但在胰腺癌中的有效性一直不足。因此，识别与免疫途径相关的标志物对于改善这种致命癌症的治疗结果至关重要。本研究的目的是调查三种标志物CD8、CD68和VISTA在胰腺癌最常见的亚型胰腺导管腺癌（PDAC）中的诊断和预后意义。
方法
我们使用生物信息学工具分析了来自基因表达综合数据库（GEO）的基因表达数据。我们还利用STRING在线工具和Funrich软件研究与CD8、CD68和VISTA相关的蛋白质-蛋白质相互作用和转录因子。此外，对228份PDAC组织样本和10份正常胰腺组织样本进行了组织微阵列（TMA）和免疫组织化学（IHC）染色，以评估这些标志物的表达水平。然后，我们将这些表达水平与患者的临床病理特征相关联，并评估他们的生存率。
结果
对GEO数据的分析显示，与正常组织相比，PDAC样本中VISTA水平略有升高。然而，胰腺癌中CD68表达显著增加，CD8A表达明显降低。进一步研究确定了与这些标志物相关的潜在蛋白质-蛋白质相互作用和转录因子。PDAC组织样本的IHC染色显示，胰腺癌组织中VISTA、CD68和CD8A表达增加。此外，我们发现这些标志物的表达水平与患者的某些临床病理特征之间存在相关性。此外，生存分析显示，CD8高表达与PDAC患者更好的疾病特异性生存和无进展生存相关。
结论
这些发现突出了CD8、CD68和VISTA作为PDAC诊断和预后指标的潜力。
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