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胃癌患者细胞外囊泡中总RNA、CD44、FASN和PTEN mRNA作为生物标志物的表征

Characterization of Total RNA, CD44, FASN, and PTEN mRNAs from Extracellular Vesicles as Biomarkers in Gastric Cancer Patients.

作者信息

Rhode Philipp, Mehdorn Matthias, Lyros Orestis, Kahlert Christoph, Kurth Thomas, Venus Tom, Schierle Katrin, Estrela-Lopis Irina, Jansen-Winkeln Boris, Lordick Florian, Gockel Ines, Thieme René

机构信息

Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, D-04103 Leipzig, Germany.

Department for Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, D-01307 Dresden, Germany.

出版信息

Cancers (Basel). 2021 Nov 27;13(23):5975. doi: 10.3390/cancers13235975.

Abstract

In-depth characterization has introduced new molecular subtypes of gastric cancer (GC). To identify these, new approaches and techniques are required. Liquid biopsies are trendsetting and provide an easy and feasible method to identify and to monitor GC patients. In a prospective cohort of 87 GC patients, extracellular vesicles (EVs) were isolated from 250 µL of plasma. The total RNA was isolated with TRIZOL. The total RNA amount and the relative mRNA levels of CD44, PTEN, and FASN were measured by qRT-PCR. The isolation of EVs and their contained mRNA was possible in all 87 samples investigated. The relative mRNA levels of PTEN were higher in patients already treated by chemotherapy than in chemo-naïve patients. In patients who had undergone neoadjuvant chemotherapy followed by gastrectomy, a decrease in the total RNA amount was observed after neoadjuvant chemotherapy and gastrectomy, while FASN and CD44 mRNA levels decreased only after gastrectomy. The amount of RNA and the relative mRNA levels of FASN and CD44 in EVs were affected more significantly by chemotherapy and gastrectomy than by chemotherapy alone. Therefore, they are a potential biomarker for monitoring treatment response. Future analyses are needed to identify GC-specific key RNAs in EVs, which could be used for the diagnosis of gastric cancer patients in order to determine their molecular subtype and to accompany the therapeutic response.

摘要

深入的特征分析揭示了胃癌(GC)的新分子亚型。为了识别这些亚型,需要新的方法和技术。液体活检引领潮流,为识别和监测GC患者提供了一种简便可行的方法。在一个由87名GC患者组成的前瞻性队列中,从250微升血浆中分离出细胞外囊泡(EVs)。用TRIZOL提取总RNA。通过qRT-PCR测量总RNA量以及CD44、PTEN和FASN的相对mRNA水平。在所研究的全部87个样本中都成功分离出了EVs及其所含的mRNA。接受过化疗的患者中PTEN的相对mRNA水平高于未接受过化疗的患者。在接受新辅助化疗后行胃切除术的患者中,新辅助化疗和胃切除术后观察到总RNA量减少,而FASN和CD44 mRNA水平仅在胃切除术后下降。与单纯化疗相比,化疗和胃切除术对EVs中RNA量以及FASN和CD44的相对mRNA水平的影响更为显著。因此,它们是监测治疗反应的潜在生物标志物。未来需要进行分析,以确定EVs中GC特异性关键RNA,可用于诊断胃癌患者,以确定其分子亚型并跟踪治疗反应。

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