Detection and significance of exosomal mRNA expression profiles in the cerebrospinal fluid of patients with meningeal ca
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Detection and significance of exosomal mRNA expression profiles in the cerebrospinal fluid of patients with meningeal carcinomatosis Peng Cheng 1 & Feifei Feng 2 & Hui Yang 1 & Suqin Jin 1 & Chao Lai 1 & Yun Wang 1
&
Jianzhong Bi 1
Received: 9 April 2020 / Accepted: 7 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Exosomes are cell-derived membrane vesicles with cargo that can be transported into receiver cells to exert their biological roles. Exosomal RNA signature profiles and exosome-derived proteomics are often used to explore the molecular regulation of diseases, and can mirror the conditional state of their tissue of origin, thus serving as biomarkers. The onset of meningeal carcinomatosis (MC) is concealed, and early diagnosis is difficult. To enable early diagnosis of MC, it is essential to identify new biomarkers. Few studies have investigated the function of exosomes in MC. In this study, high-throughput sequencing was used to examine the mRNA profiles of exosomes in the cerebrospinal fluid (CSF) of patients with MC. We further analyzed the functions and signaling pathways associated with the differentially expressed genes in exosomes to reveal the putative mechanisms by which the exosomal mRNAs function in MC. In summary, this study identified biomarker candidates for MC, and provided new insights into the significant role of exosomal mRNA regulation in MC. Keywords Meningeal carcinomatosis . Exosomes . mRNA profiling . Cerebrospinal fluid
Introduction Meningeal carcinomatosis (MC) refers to the metastasis of various malignant tumors to the dura mater, pia mater, cerebrospinal fluid, and subarachnoid space, and represents a serious complication of the central nervous system in advancedstage cancer patients (Groves 2011). Generally, there are no tumors in the brain and spinal cord. However, approximately 10%–30% of patients with solid tumors develop central nervous system (CNS) metastasis; of these, 4%–15% have MC (Aragon-Ching and Zujewski 2007), which is highly malignant and has poor prognosis. MC is easily confused with meningitis because it lacks specific clinical manifestations. * Chao Lai [email protected] * Yun Wang [email protected] 1
Department of Neural Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, People’s Republic of China
2
Department of Respiratory Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, People’s Republic of China
Additionally, many patients with MC do not have previous history of malignant tumors, and the first manifestation of CNS disease can often be undiagnosed or misdiagnosed (Van Horn and Chamberlain 2012). Early diagnosis and treatment are essential to improve the prognosis of patients with MC and reduce their mortality. Therefore, it is important to develop effective methods for early diagnosis of MC. Exosomes are a type of cell-derived membrane microvesicle (40–100 nm in diameter), which are secreted
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