The mtDNA fragments within exosomes might be novel diagnostic biomarkers of non-small cell lung cancer

被引:5
作者
Lou, Chengtao [1 ,2 ]
Ma, Xinyi [1 ,2 ]
Chen, Zhenhua [1 ,2 ]
Zhao, Yikai [1 ,2 ]
Yao, Qunsheng [1 ,2 ]
Zhou, Chengwei [3 ]
Zhao, Xiaodong [3 ]
Meng, Xiaodan [1 ,2 ]
机构
[1] Ningbo Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Ningbo 315211, Zhejiang, Peoples R China
[2] Ningbo Univ, Hlth Sci Ctr, Zhejiang Prov Key Lab Pathophysiol, Ningbo 315211, Zhejiang, Peoples R China
[3] Ningbo Univ, Affiliated Hosp 1, Dept Thorac Surg, Ningbo 315020, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Non-small cell lung cancer; Exosomes; Mitochondrial DNAs; Tumor markers; Diagnosis; CIRCULATING MITOCHONDRIAL-DNA; QUANTIFICATION; PLASMA; BREAST; BLOOD; SERUM;
D O I
10.1016/j.prp.2023.154718
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Background: A portion of circulating mtDNAs is encapsulated in exosomes, but their contribution to cancers is rarely studied. We aim to investigate the diagnostic potential of exosomal mtDNA content for non-small cell lung cancer (NSCLC). Methods: Exosomes were isolated from plasma and identified by western blot, scanning electron microscopy, and particle size analysis. The plasma and plasma exosomal mtDNA fragment levels (mtDNA79, mtDNA230, and MTATP8) in healthy, pneumonia, benign lung tumors, and NSCLC were quantified by qPCR. Statistical analyses were performed to compare the levels of mtDNA fragments in different subgroups. ROC analyses were used to evaluate mtDNA fragments' diagnostic sensitivity and specificity. Results: We found that plasma mtDNAs were partially present in exosomes. Both plasma and exosomal mtDNA fragments (mtDNA79, mtDNA230, and MTATP8) were increased in NSCLC, particularly more malignant NSCLC. Compared to plasma mtDNAs and traditional tumor markers, exosomal mtDNAs are more closely associated with aggressive features of NSCLC, like bigger tumor sizes, advanced stages, lymph node metastasis, and distant metastasis, showing higher sensitivity and specificity to diagnose NSCLC. Conclusions: Changed contents of plasma and plasma exosomal mtDNAs show great potential to diagnose NSCLC, and exosomal mtDNAs might be promising biomarkers for more aggressive NSCLC.
引用
收藏
页数:10
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共 37 条
[31]   Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma [J].
Vagner, Tatyana ;
Spinelli, Cristiana ;
Minciacchi, Valentina R. ;
Balaj, Leonora ;
Zandian, Mandana ;
Conley, Andrew ;
Zijlstra, Andries ;
Freeman, Michael R. ;
Demichelis, Francesca ;
De, Subhajyoti ;
Posadas, Edwin M. ;
Tanaka, Hisashi ;
Di Vizio, Dolores .
JOURNAL OF EXTRACELLULAR VESICLES, 2018, 7 (01)
[32]   Double-stranded DNA in exosomes: a novel biomarker in cancer detection [J].
Williams, Caitlin ;
Rodriguez-Barrueco, Ruth ;
Silva, Jose M. ;
Zhang, Weijia ;
Hearn, Stephen ;
Elemento, Olivier ;
Paknejad, Navid ;
Manova-Todorova, Katia ;
Welte, Karl ;
Bromberg, Jacqueline ;
Peinado, Hector ;
Lyden, David .
CELL RESEARCH, 2014, 24 (06) :766-769
[33]   The application of CA72-4 in the diagnosis, prognosis, and treatment of gastric cancer [J].
Xu, Yitian ;
Zhang, Pengshan ;
Zhang, Kundong ;
Huang, Chen .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2021, 1876 (02)
[34]   Pre-diagnostic leukocyte mitochondrial DNA copy number and colorectal cancer risk [J].
Yang, Keming ;
Li, Xin ;
Forman, Michele R. ;
Monahan, Patrick O. ;
Graham, Bret H. ;
Joshi, Amit ;
Song, Mingyang ;
Hang, Dong ;
Ogino, Shuji ;
Giovannucci, Edward L. ;
De Vivo, Immaculata ;
Chan, Andrew T. ;
Nan, Hongmei .
CARCINOGENESIS, 2019, 40 (12) :1462-1468
[35]   Circulating cell-free mitochondrial DNA as a novel cancer biomarker: opportunities and challenges [J].
Yu, Man .
MITOCHONDRIAL DNA, 2012, 23 (05) :329-332
[36]   Exosomes in cancer development, metastasis, and immunity [J].
Zhang, Lin ;
Yu, Dihua .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2019, 1871 (02) :455-468
[37]   Next-Generation Sequencing-Based Analysis of Urine Cell-Free mtDNA Reveals Aberrant Fragmentation and Mutation Profile in Cancer Patients [J].
Zhou, Kaixiang ;
Liu, Yang ;
Yuan, Qing ;
Lai, Dong ;
Guo, Shanshan ;
Wang, Zhenni ;
Su, Liping ;
Zhang, Huanqin ;
Wang, Xiangxu ;
Guo, Wenjie ;
Ji, Xiaoying ;
Gu, Xiwen ;
Huang, Qichao ;
Guo, Xu ;
Xing, Jinliang .
CLINICAL CHEMISTRY, 2022, 68 (04) :561-573