Altered exosomal miRNA profiles in patients with paraneoplastic cerebellar degeneration.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
29 Oct 2024
29 Oct 2024
Historique:
revised:
25
09
2024
received:
11
07
2024
accepted:
04
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
aheadofprint
Résumé
Patients with ovarian cancer (OC) may develop anti-Yo-associated paraneoplastic cerebellar degeneration (PCD)-a cerebellar ataxia associated with tumor-induced autoimmunity against CDR2 and CDR2L proteins. Dysregulation of circulating exosomal microRNAs (miRNAs) occur in OC. Here, we investigated whether PCD is associated with changes in the exosomal miRNA profiles of OC patients. Serum exosomes were isolated from patients with OC (n = 15), patients with OC and anti-Yo-associated PCD (n = 14) and healthy controls (HC, n = 15). Small RNA sequencing was used to identify differentially expressed miRNAs. Receiver operating characteristic curves were used to evaluate biomarker sensitivity and specificity, and miRNA target prediction analysis was employed to elucidate gene targets. OC patients with PCD exhibited a distinct exosomal miRNA expression profile. We detected 103 differentially expressed exosomal miRNAs in PCD patients compared to OC patients without PCD and 139 differentially expressed exosomal miRNAs compared to controls. Particularly miR-486-5p, miR-4732-5p, miR-98-5p and miR-21-5p exhibited notable sensitivity and specificity for discriminating PCD patients from both OC patients without PCD and healthy controls. miRNA target prediction showed that several of the differentially expressed miRNAs in PCD patients targeted the CDR2 and CDR2L genes. Our results demonstrate that OC patients with anti-Yo-associated PCD exhibit a distinct exosomal miRNA profile compared to OC patients without PCD. Several of the differentially expressed exosomal miRNAs in PCD patients showed diagnostic potential and may hold relevance for understanding the pathogenesis of PCD.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Gerda Meyer Nyquist Gulbranson & Gerdt Meyer Nyquist Legacy
ID : 102230101
Informations de copyright
© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Venkatraman A, Opal P. Paraneoplastic cerebellar degeneration with anti‐Yo antibodies ‐ a review. Ann Clin Transl Neurol. 2016;3(8):655‐663.
Graus F, Vogrig A, Muñiz‐Castrillo S, et al. Updated diagnostic criteria for paraneoplastic neurologic syndromes. Neurol Neuroimmunol Neuroinflamm. 2021;8(4):e1014.
Loehrer PA, Zieger L, Simon OJ. Update on paraneoplastic cerebellar degeneration. Brain Sci. 2021;11(11):1414.
Ducray F, Demarquay G, Graus F, et al. Seronegative paraneoplastic cerebellar degeneration: the PNS Euronetwork experience. Eur J Neurol. 2014;21(5):731‐735.
McKeon A, Tracy JA, Pittock SJ, Parisi JE, Klein CJ, Lennon VA. Purkinje cell cytoplasmic autoantibody type 1 accompaniments: the cerebellum and beyond. Arch Neurol. 2011;68(10):1282‐1289.
Monstad SE, Storstein A, Dørum A, et al. Yo antibodies in ovarian and breast cancer patients detected by a sensitive immunoprecipitation technique. Clin Exp Immunol. 2006;144(1):53‐58.
Fathallah‐Shaykh H, Wolf S, Wong E, Posner JB, Furneaux HM. Cloning of a leucine‐zipper protein recognized by the sera of patients with antibody‐associated paraneoplastic cerebellar degeneration. Proc Natl Acad Sci USA. 1991;88(8):3451‐3454.
Eichler TW, Totland C, Haugen M, et al. CDR2L antibodies: a new player in paraneoplastic cerebellar degeneration. PLoS One. 2013;8(6):e66002.
Kråkenes T, Herdlevaer I, Raspotnig M, et al. CDR2L is the major Yo antibody target in paraneoplastic cerebellar degeneration. Ann Neurol. 2019;86(2):316‐321.
Herdlevaer I, Kråkenes T, Schubert M, Vedeler CA. Localization of CDR2L and CDR2 in paraneoplastic cerebellar degeneration. Ann Clin Transl Neurol. 2020;7(11):2231‐2242.
Small M, Treilleux I, Couillault C, et al. Genetic alterations and tumor immune attack in Yo paraneoplastic cerebellar degeneration. Acta Neuropathol. 2018;135(4):569‐579.
Peter E, Treilleux I, Wucher V, et al. Immune and genetic signatures of breast carcinomas triggering anti‐Yo–associated paraneoplastic cerebellar degeneration. Neurol Neuroimmunol Neuroinflamm. 2022;9(5):e200015.
Barros FM, Carneiro F, Machado JC, Melo SA. Exosomes and immune response in cancer: friends or foes? Front Immunol. 2018;9:730.
Goldie BJ, Dun MD, Lin M, et al. Activity‐associated miRNA are packaged in Map1b‐enriched exosomes released from depolarized neurons. Nucleic Acids Res. 2014;42(14):9195‐9208.
Guduric‐Fuchs J, O'Connor A, Camp B, et al. Selective extracellular vesicle‐mediated export of an overlapping set of microRNAs from multiple cell types. BMC Genomics. 2012;13:357.
Li Y, Gu J, Mao Y, et al. Cerebrospinal fluid extracellular vesicles with distinct properties in autoimmune encephalitis and herpes simplex encephalitis. Mol Neurobiol. 2022;59(4):2441‐2455.
Ebrahimkhani S, Vafaee F, Young PE, et al. Exosomal microRNA signatures in multiple sclerosis reflect disease status. Sci Rep. 2017;7(1):14293.
Gui Y, Liu H, Zhang L, Lv W, Hu XY. Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease. Oncotarget. 2015;6(35):37043‐37053.
Elias KM, Fendler W, Stawiski K, et al. Diagnostic potential for a serum miRNA neural network for detection of ovarian cancer. elife. 2017;6:6.
Gahlawat AW, Witte T, Haarhuis L, Schott S. A novel circulating miRNA panel for non‐invasive ovarian cancer diagnosis and prognosis. Br J Cancer. 2022;127(8):1550‐1556.
Frisk NLS, Sørensen AE, Pedersen OBV, Dalgaard LT. Circulating microRNAs for early diagnosis of ovarian cancer: a systematic review and meta‐analysis. Biomolecules. 2023;13(5):871.
Berek JS, Renz M, Kehoe S, Kumar L, Friedlander M. Cancer of the ovary, fallopian tube, and peritoneum: 2021 update. Int J Gynaecol Obstet. 2021;155(Suppl 1):61‐85.
Patil AH, Halushka MK. miRge3.0: a comprehensive microRNA and tRF sequencing analysis pipeline. NAR Genom Bioinform. 2021;3(3):lqab068.
Martin M. Cutadapt removes adapter sequences from high‐throughput sequencing reads. EMBnet J. 2011;17(1):3.
Kozomara A, Birgaoanu M, Griffiths‐Jones S. miRBase: from microRNA sequences to function. Nucleic Acids Res. 2019;47(D1):D155‐D162.
Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory‐efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10(3):R25.
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA‐seq data with DESeq2. Genome Biol. 2014;15(12):550.
Wickham H, Averick M, Bryan J, et al. Welcome to the Tidyverse. J Open Source Softw. 2019;4(43):1686.
Skoufos G, Kakoulidis P, Tastsoglou S, et al. TarBase‐v9.0 extends experimentally supported miRNA–gene interactions to cell‐types and virally encoded miRNAs. Nucleic Acids Res. 2023;52(D1):D304‐D310.
Tastsoglou S, Skoufos G, Miliotis M, et al. DIANA‐miRPath v4.0: expanding target‐based miRNA functional analysis in cell‐type and tissue contexts. Nucleic Acids Res. 2023;51(W1):W154‐W159.
Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro‐Watanabe M. KEGG for taxonomy‐based analysis of pathways and genomes. Nucleic Acids Res. 2023;51(D1):D587‐D592.
Robin X, Turck N, Hainard A, et al. pROC: an open‐source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011;12(1):77.
Xu H, Bao Z, Liang D, et al. Plasma exosomal miR‐106a‐5p expression in myasthenia gravis. Muscle Nerve. 2020;61(3):401‐407.
Wang L, Zhang L. Circulating Exosomal miRNA as diagnostic biomarkers of neurodegenerative diseases. Front Mol Neurosci. 2020;13:53.
Lu L‐F, Boldin MP, Chaudhry A, et al. Function of miR‐146a in controlling Treg cell‐mediated regulation of Th1 responses. Cell. 2010;142(6):914‐929.
Taheri F, Ebrahimi SO, Shareef S, Reiisi S. Regulatory and immunomodulatory role of miR‐34a in T cell immunity. Life Sci. 2020;262:118209.
Ridder K, Keller S, Dams M, et al. Extracellular vesicle‐mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation. PLoS Biol. 2014;12(6):e1001874.
Greenlee JE, Clawson SA, Hill KE, et al. Anti‐Yo antibody uptake and interaction with its intracellular target antigen causes Purkinje cell death in rat cerebellar slice cultures: a possible mechanism for paraneoplastic cerebellar degeneration in humans with gynecological or breast cancers. PLoS One. 2015;10(4):e0123446.
Panja D, Vedeler CA, Schubert M. Paraneoplastic cerebellar degeneration: Yo antibody alters mitochondrial calcium buffering capacity. Neuropathol Appl Neurobiol. 2019;45(2):141‐156.
Tanaka K, Tanaka M, Onodera O, Igarashi S, Miyatake T, Tsuji S. Passive transfer and active immunization with the recombinant leucine‐zipper (Yo) protein as an attempt to establish an animal model of paraneoplastic cerebellar degeneration. J Neurol Sci. 1994;127(2):153‐158.
Graus F, Illa I, Agusti M, Ribalta T, Cruz‐Sanchez F, Juarez C. Effect of intraventricular injection of an anti‐Purkinje cell antibody (anti‐Yo) in a Guinea pig model. J Neurol Sci. 1991;106(1):82‐87.
Faure F, Yshii L, Renno T, et al. A pilot study to develop paraneoplastic cerebellar degeneration mouse model. Cerebellum (London, England). 2024;23(1):181‐196.
Sullivan R, Yau WY, O'Connor E, Houlden H. Spinocerebellar ataxia: an update. J Neurol. 2019;266(2):533‐544.
Hornung S, Dutta S, Bitan G. CNS‐derived blood exosomes as a promising source of biomarkers: opportunities and challenges. Front Mol Neurosci. 2020;13:38.
Theodoraki MN, Hoffmann TK, Whiteside TL. Separation of plasma‐derived exosomes into CD3((+)) and CD3((−)) fractions allows for association of immune cell and tumour cell markers with disease activity in HNSCC patients. Clin Exp Immunol. 2018;192(3):271‐283.
Sharma P, Ludwig S, Muller L, et al. Immunoaffinity‐based isolation of melanoma cell‐derived exosomes from plasma of patients with melanoma. J Extracell Vesicles. 2018;7(1):1435138.
Mohammadinasr M, Montazersaheb S, Molavi O, et al. Multiplex analysis of cerebrospinal fluid and serum exosomes MicroRNAs of untreated relapsing remitting multiple sclerosis (RRMS) and proposing noninvasive diagnostic biomarkers. NeuroMolecular Med. 2023;25(3):402‐414.
Gu J, Jin T, Li Z, et al. Exosomes expressing neuronal autoantigens induced immune response in antibody‐positive autoimmune encephalitis. Mol Immunol. 2021;131:164‐170.
Déchelotte B, Muñiz‐Castrillo S, Joubert B, et al. Diagnostic yield of commercial immunodots to diagnose paraneoplastic neurologic syndromes. Neurol Neuroimmunol Neuroinflamm. 2020;7(3):e701.
Erikstad KI, Herdlevaer I, Peter E, et al. A cerebellar degeneration‐related protein 2‐like cell‐based assay for anti‐Yo detection in patients with paraneoplastic cerebellar degeneration. Eur J Neurol. 2023;30(6):1727‐1733.
Nasu M, Khadka VS, Jijiwa M, Kobayashi K, Deng Y. Exploring optimal biomarker sources: a comparative analysis of exosomes and whole plasma in fasting and non‐fasting conditions for liquid biopsy applications. Int J Mol Sci. 2024;25(1):371.
Van Deun J, Mestdagh P, Sormunen R, et al. The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling. J Extracell Vesicles. 2014;3:24858.
Piket E, Zheleznyakova GY, Kular L, Jagodic M. Small non‐coding RNAs as important players, biomarkers and therapeutic targets in multiple sclerosis: a comprehensive overview. J Autoimmun. 2019;101:17‐25.
Meng X, Müller V, Milde‐Langosch K, Trillsch F, Pantel K, Schwarzenbach H. Diagnostic and prognostic relevance of circulating exosomal miR‐373, miR‐200a, miR‐200b and miR‐200c in patients with epithelial ovarian cancer. Oncotarget. 2016;7(13):16923‐16935.
Yu X, Zhang X, Bi T, et al. MiRNA expression signature for potentially predicting the prognosis of ovarian serous carcinoma. Tumour Biol. 2013;34(6):3501‐3508.
Pan C, Stevic I, Müller V, et al. Exosomal microRNAs as tumor markers in epithelial ovarian cancer. Mol Oncol. 2018;12(11):1935‐1948.
Liu J, Yoo J, Ho JY, et al. Plasma‐derived exosomal miR‐4732‐5p is a promising noninvasive diagnostic biomarker for epithelial ovarian cancer. J Ovarian Res. 2021;14(1):59.
Kang E, Jung SC, Nam SK, et al. Tissue miR‐200c‐3p and circulating miR‐1290 as potential prognostic biomarkers for colorectal cancer. Sci Rep. 2022;12(1):2295.
Paik WH, Song BJ, Kim HW, Kim HR, Hwang JH. MicroRNA‐200c as a prognostic biomarker for pancreatic cancer. Korean J Gastroenterol. 2015;66(4):215‐220.
de la Cruz‐Ojeda P, Schmid T, Boix L, et al. miR‐200c‐3p, miR‐222‐5p, and miR‐512‐3p constitute a biomarker signature of sorafenib effectiveness in advanced hepatocellular carcinoma. Cells. 2022;11(17):2673.