Circulating Monocytes Serve as Novel Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma Patients.
Circulating Monocytes Serve as Novel Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma Patients.
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循环单核细胞是胰腺导管腺癌患者的新型预后生物标志物。
DOI：
10.3390/cancers15020363
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发表时间：
2023-01-05
期刊：
影响因子：
5.2
通讯作者：
Weber, Georg F.
中科院分区：
文献类型：
--
作者：
Hansen, Frederik J.;David, Paul;Akram, Marina;Knoedler, Samuel;Mittelstaedt, Anke;Merkel, Susanne;Podolska, Malgorzata J.;Swierzy, Izabela;Rossdeutsch, Lotta;Kloesch, Bettina;Kouhestani, Dina;Anthuber, Anna;Benard, Alan;Brunner, Maximilian;Krautz, Christian;Gruetzmann, Robert;Weber, Georg F.
关键词：
胰腺导管腺癌（Pancreatic ductal adencarcinoma， PDAC）是最致命的恶性疾病之一。单核细胞与较差结果的关联已被证明适用于广泛的恶性肿瘤。然而，它们在PDAC中的作用仍有待阐明。在这项研究中，我们发现PDAC患者中循环单核细胞水平升高，与更积极的肿瘤生长和更低的生存率相关。因此，我们提出单核细胞可能作为PDAC的一种新的预后生物标志物。未来需要大规模的研究来研究单核细胞作为潜在的治疗靶点。胰腺导管腺癌（PDAC）是最致命的癌症疾病之一，被广泛认为预后最糟糕。尽管免疫疗法广泛地改变了癌症治疗，但其在PDAC中的价值似乎相对较低。单核细胞表现出肿瘤效应，最近被认为是这种免疫治疗方案的潜在靶点。然而，到目前为止，关于单核细胞在PDAC中的作用的证据很少。因此，我们在手术前分析了58例PDAC患者外周血中的单核细胞，并将其与健康人进行了比较。与健康对照相比，PDAC患者单核细胞水平升高，此外，与非浸润性肿瘤相比，神经周围浸润的患者单核细胞比例更高，PDAC G3的单核细胞水平高于PDAC G2。与单核细胞水平低于5%的患者相比，单核细胞水平低于5%的患者发生G3和神经周围浸润性PDAC的风险增加8.9倍，导致生存期较差。此外，与健康个体相比，PDAC患者单核细胞CD86和CD11c的表达增加，PD-L1的表达减少。最后，PDAC患者血浆中单核细胞水平与IL-6和TNF-α浓度呈正相关。基于我们的发现，我们提出单核细胞作为一种新的预后生物标志物。需要大规模的研究来进一步解读单核细胞在PDAC中的作用，并研究它们作为治疗靶点的潜力。
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant diseases. The association of monocytes with worse outcomes has been demonstrated for a wide array of malignancies. Yet, their role in PDAC remains to be elucidated. In this study, we found elevated levels of circulating monocytes in PDAC patients, correlating with more aggressive tumor growth and decreased survival. Therefore, we propose that monocytes may act as a novel prognostic biomarker for PDAC. Future large-scale studies are needed to investigate monocytes as potential therapeutic targets. Pancreatic ductal adenocarcinoma (PDAC) ranks among the most fatal cancer diseases, widely accepted to have the most dismal prognoses. Although immunotherapy has broadly revolutionized cancer treatment, its value in PDAC appears to be relatively low. Exhibiting protumoral effects, monocytes have recently been proposed as potential targets of such immunotherapeutic regimens. However, to date, the body of evidence on monocytes’ role in PDAC is scarce. Therefore, we analyzed monocytes in the peripheral blood of 58 PDAC patients prior to surgery and compared them to healthy individuals. PDAC patients showed increased levels of monocytes when compared to healthy controls In addition, patients with perineural infiltration demonstrated a higher percentage of monocytes compared to non-infiltrating tumors and PDAC G3 was associated with higher monocyte levels than PDAC G2. Patients with monocyte levels > 5% were found to have an 8.9-fold increased risk for a G3 and perineural infiltrated PDAC resulting in poorer survival compared to patients with <5% monocyte levels. Furthermore, PDAC patients showed increased expressions of CD86 and CD11c and decreased expressions of PD-L1 on monocytes compared to healthy individuals. Finally, levels of monocytes correlated positively with concentrations of IL-6 and TNF-α in plasma of PDAC patients. Based on our findings, we propose monocytes as a novel prognostic biomarker. Large-scale studies are needed to further decipher the role of monocytes in PDAC and investigate their potential as therapeutic targets.
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