PDF(Pubmed)
Abstract：
UNASSIGNED: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and peritoneal dissemination is one major cause for this poor prognosis. Exosomes have emerged as promising biomarkers for gastrointestinal cancers and can be found in all kinds of bodily fluids, also in peritoneal fluid (PF). This is a unique sample due to its closeness to gastrointestinal malignancies. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) has been identified as a potential biomarker in human cancers and represents a promising target for an immunotherapy approach, which could be considered for future treatment strategies. Here we prospectively analyzed the exosomal surface protein ROR1 (exo-ROR1) in PF in localized PDAC patients (PER-) on the one hand and peritoneal disseminated tumor stages (PER+) on the other hand followed by the correlation of exo-ROR1 with clinical-pathological parameters.
UNASSIGNED: Exosomes were isolated from PF and plasma samples of non-cancerous (NC) (n = 15), chronic pancreatitis (CP) (n = 4), localized PDAC (PER-) (n = 18) and peritoneal disseminated PDAC (PER+) (n = 9) patients and the surface protein ROR1 was detected via FACS analysis. Additionally, soluble ROR1 in PF was analyzed. ROR1 expression in tissue was investigated using western blots (WB), qPCR, and immunohistochemistry (IHC). Exosome isolation was proven by Nano Tracking Analysis (NTA), WB, Transmission electron microscopy (TEM), and BCA protein assay. The results were correlated with clinical data and survival analysis was performed.
UNASSIGNED: PDAC (PER+) patients have the highest exo-ROR1 values in PF and can be discriminated from NC (p <0.0001), PDAC (PER-) (p <0.0001), and CP (p = 0.0112). PDAC (PER-) can be discriminated from NC (p = 0.0003). In plasma, exo-ROR1 is not able to distinguish between the groups. While there is no expression of ROR1 in the exocrine pancreatic tissue, PDAC and peritoneal metastasis show expression of ROR1. High exo-ROR1 expression in PF is associated with lower overall survival (p = 0.0482).
UNASSIGNED: With exo-ROR1 in PF we found a promising diagnostic and prognostic biomarker possibly discriminating between NC, PDAC (PER-) and PDAC (PER+) and might shed light on future diagnostic and therapeutic concepts in PDAC.
UNASSIGNED: Exosomes were isolated from PF and plasma samples of non-cancerous (NC) (n = 15), chronic pancreatitis (CP) (n = 4), localized PDAC (PER-) (n = 18) and peritoneal disseminated PDAC (PER+) (n = 9) patients and the surface protein ROR1 was detected via FACS analysis. Additionally, soluble ROR1 in PF was analyzed. ROR1 expression in tissue was investigated using western blots (WB), qPCR, and immunohistochemistry (IHC). Exosome isolation was proven by Nano Tracking Analysis (NTA), WB, Transmission electron microscopy (TEM), and BCA protein assay. The results were correlated with clinical data and survival analysis was performed.
UNASSIGNED: PDAC (PER+) patients have the highest exo-ROR1 values in PF and can be discriminated from NC (p <0.0001), PDAC (PER-) (p <0.0001), and CP (p = 0.0112). PDAC (PER-) can be discriminated from NC (p = 0.0003). In plasma, exo-ROR1 is not able to distinguish between the groups. While there is no expression of ROR1 in the exocrine pancreatic tissue, PDAC and peritoneal metastasis show expression of ROR1. High exo-ROR1 expression in PF is associated with lower overall survival (p = 0.0482).
UNASSIGNED: With exo-ROR1 in PF we found a promising diagnostic and prognostic biomarker possibly discriminating between NC, PDAC (PER-) and PDAC (PER+) and might shed light on future diagnostic and therapeutic concepts in PDAC.
摘要：
■胰腺导管腺癌（PDAC）是最致命的癌症之一，腹膜播散是预后不良的主要原因之一。外泌体已经成为胃肠道癌症的有希望的生物标志物，可以在各种体液中发现，也在腹膜液（PF）。这是一个独特的样品，因为它接近胃肠道恶性肿瘤。受体酪氨酸激酶样孤儿受体1（ROR1）已被确定为人类癌症的潜在生物标志物，并代表了免疫治疗方法的有希望的靶标。这可以考虑为未来的治疗策略。在这里，我们前瞻性地分析了一方面是局部PDAC患者（PER-）中PF中的外泌体表面蛋白ROR1（exo-ROR1），另一方面是腹膜播散性肿瘤分期（PER），然后是exo-ROR1与临床病理参数的相关性。
■从PF和非癌（NC）的血浆样品中分离外泌体（n=15），慢性胰腺炎（CP）（n=4），局部PDAC(PER-)(n=18)和腹膜播散性PDAC(PER+)(n=9)患者,通过FACS分析检测到表面蛋白ROR1.此外,分析了PF中可溶性ROR1。使用蛋白质印迹(WB)研究组织中的ROR1表达,qPCR,免疫组织化学（IHC）。通过纳米跟踪分析（NTA）证明了外泌体隔离，WB,透射电子显微镜(TEM),和BCA蛋白测定。结果与临床资料相关，并进行生存分析。
■PDAC（PER）患者在PF中具有最高的exo-ROR1值，可以与NC区分开（p<0.0001），PDAC(PER-)(p<0.0001)，和CP（p=0.0112）。PDAC(PER-)可以与NC(p=0.0003)区分开。在等离子体中，exo-ROR1不能区分这些基团。虽然在胰腺外分泌组织中没有ROR1的表达，PDAC和腹膜转移显示ROR1表达。PF中的高exo-ROR1表达与较低的总生存率相关(p=0.0482)。
■在PF中使用exo-ROR1，我们发现了一种有希望的诊断和预后生物标志物，可能区分NC，PDAC(PER-)和PDAC(PER+)，并可能阐明PDAC未来的诊断和治疗概念。
■从PF和非癌（NC）的血浆样品中分离外泌体（n=15），慢性胰腺炎（CP）（n=4），局部PDAC(PER-)(n=18)和腹膜播散性PDAC(PER+)(n=9)患者,通过FACS分析检测到表面蛋白ROR1.此外,分析了PF中可溶性ROR1。使用蛋白质印迹(WB)研究组织中的ROR1表达,qPCR,免疫组织化学（IHC）。通过纳米跟踪分析（NTA）证明了外泌体隔离，WB,透射电子显微镜(TEM),和BCA蛋白测定。结果与临床资料相关，并进行生存分析。
■PDAC（PER）患者在PF中具有最高的exo-ROR1值，可以与NC区分开（p<0.0001），PDAC(PER-)(p<0.0001)，和CP（p=0.0112）。PDAC(PER-)可以与NC(p=0.0003)区分开。在等离子体中，exo-ROR1不能区分这些基团。虽然在胰腺外分泌组织中没有ROR1的表达，PDAC和腹膜转移显示ROR1表达。PF中的高exo-ROR1表达与较低的总生存率相关(p=0.0482)。
■在PF中使用exo-ROR1，我们发现了一种有希望的诊断和预后生物标志物，可能区分NC，PDAC(PER-)和PDAC(PER+)，并可能阐明PDAC未来的诊断和治疗概念。
