Fengming Lan1, Qin Qing2, Qiang Pan3, Man Hu4, Huiming Yu5, Xiao Yue6. 1. Department of Radiation Oncology, Tianjin Hospital, 406 Jiefangnan Road, Tianjin, 300211, People's Republic of China. 2. Department of Radiation Oncology, PLA Airforce General Hospital of Anhui Medical University, Beijing, 100142, People's Republic of China. 3. Department of Neurosurgery, Laiwu City People's Hospital, Laiwu, Shandong Province, 271100, People's Republic of China. 4. Departments of Radiation Oncology and Shandong Province Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, Shandong, 250117, People's Republic of China. 5. Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of radiotherapy, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Beijin, 100142, People's Republic of China. huiming740512@163.com. 6. Tianjin Huanhu Hospital, Tianjin Neurosurgery Institute, 6 Jizhao Road, Tianjin, 300350, People's Republic of China. yuexiaolfm@163.com.
Abstract
PURPOSE: Exosomal miRNAs that play an important role in cell-cell communication have attracted major attention as potential diagnostic and prognostic biomarkers for various cancers. The aim of this study was to determine the diagnostic/prognostic significance of serum exosomal miR-301a in glioma patients. METHODS: Quantitative real-time PCR was used to determine the serum exosomal expression levels of miR-301a. Kaplan-Meier survival analyses, Cox regression analyses and ROC working curve analyses were applied to assess the diagnostic and prognostic values of miR-301a in glioma patients. Also, several in vitro assays were used, including proliferation, invasion and cell signaling assays. RESULTS: First, we established that serum exosomal miR-301a extracted from grade IV glioblastoma (GBM) patients was biologically active, i.e., promoted the proliferation and invasion of glioma-derived H4 cells. Subsequently, we found that serum exosomal miR-301a levels were significantly up-regulated in glioma patients compared to healthy controls. Additionally, we found that increased serum exosomal miR-301a levels were correlated with ascending pathological grades and lower Karnofsky performance status (KPS) scores. Importantly, we also found that the serum exosomal miR-301a levels were significantly reduced after surgical resection of primary tumors and increased again during GBM recurrence. Kaplan-Meier analysis of patients with an advanced pathological grade (III or IV) and an increased serum exosomal miR-301a level revealed a longer overall survival (OS) compared to those with a lower level (p < 0.01). Both univariate and multivariate Cox regression analyses confirmed that serum exosomal miR-301a levels are independently associated with OS. Finally, we found that miR-301a may activate the AKT and FAK signaling pathways by down regulating PTEN. CONCLUSIONS: Our data indicate that serum exosomal miR-301a levels may reflect the cancer-bearing status and pathological changes in glioma patients. Serum exosomal miR-301a expression may serve as a novel biomarker for glioma diagnosis and as a prognostic factor for advanced grade disease.
PURPOSE: Exosomal miRNAs that play an important role in cell-cell communication have attracted major attention as potential diagnostic and prognostic biomarkers for various cancers. The aim of this study was to determine the diagnostic/prognostic significance of serum exosomal miR-301a in gliomapatients. METHODS: Quantitative real-time PCR was used to determine the serum exosomal expression levels of miR-301a. Kaplan-Meier survival analyses, Cox regression analyses and ROC working curve analyses were applied to assess the diagnostic and prognostic values of miR-301a in gliomapatients. Also, several in vitro assays were used, including proliferation, invasion and cell signaling assays. RESULTS: First, we established that serum exosomal miR-301a extracted from grade IV glioblastoma (GBM) patients was biologically active, i.e., promoted the proliferation and invasion of glioma-derived H4 cells. Subsequently, we found that serum exosomal miR-301a levels were significantly up-regulated in gliomapatients compared to healthy controls. Additionally, we found that increased serum exosomal miR-301a levels were correlated with ascending pathological grades and lower Karnofsky performance status (KPS) scores. Importantly, we also found that the serum exosomal miR-301a levels were significantly reduced after surgical resection of primary tumors and increased again during GBM recurrence. Kaplan-Meier analysis of patients with an advanced pathological grade (III or IV) and an increased serum exosomal miR-301a level revealed a longer overall survival (OS) compared to those with a lower level (p < 0.01). Both univariate and multivariate Cox regression analyses confirmed that serum exosomal miR-301a levels are independently associated with OS. Finally, we found that miR-301a may activate the AKT and FAK signaling pathways by down regulating PTEN. CONCLUSIONS: Our data indicate that serum exosomal miR-301a levels may reflect the cancer-bearing status and pathological changes in gliomapatients. Serum exosomal miR-301a expression may serve as a novel biomarker for glioma diagnosis and as a prognostic factor for advanced grade disease.
Authors: T Matsumura; K Sugimachi; H Iinuma; Y Takahashi; J Kurashige; G Sawada; M Ueda; R Uchi; H Ueo; Y Takano; Y Shinden; H Eguchi; H Yamamoto; Y Doki; M Mori; T Ochiya; K Mimori Journal: Br J Cancer Date: 2015-06-09 Impact factor: 7.640
Authors: Anudeep Yekula; Koushik Muralidharan; Zachary S Rosh; Anna E Youngkin; Keiko M Kang; Leonora Balaj; Bob S Carter Journal: Adv Biosyst Date: 2020-06-02