Abstract
Cerebral venous thrombosis (CVT), a rare type of cerebrovascular disease, can mimic a brain tumor (CVT mimicking brain tumor [CVTMBT]), due to its space-occupying imaging features. We aimed to describe the clinicopathological features and identify the thrombophilia-related gene expression changes in the brain following CVT. We conducted a retrospective qualitative study of CVT patients who were misdiagnosed with brain tumors before surgery at our hospital from 2016 to 2021. We analyzed the clinicopathological characteristics of the cases from our hospital and previously published cases. Five subjects were retrospectively studied, but one refused to provide biological specimens. We performed messenger ribonucleic acid (mRNA) sequencing from eight specimens (four CVTMBT and four non-CVTMBT samples). Differentially expressed genes (DEGs) were screened using the “edge” package in R 3.6.1 software. Thrombophilia-related genes were obtained from the MalaCards human disease database and were cross-checked with DEGs. The intersection was considered to be the potential genes in the pathogenesis of CVTMBT. The medical histories of the five patients with CVTMBT included oral non-steroidal anti-inflammatory drug use, oral contraceptive use, cesarean section, and anemia. All patients underwent craniotomy and were pathologically diagnosed with CVT. The follow-up results revealed that all patients had favorable outcomes without any recurrence. DEG analysis revealed 813 upregulated and 253 downregulated DEGs between patients with CVTMBT and controls. Nine DEGs were associated with thrombophilia, including SERPINE1, SELP, THBD, ITGB3, TFPI, F13A1, PROS1, PPBP, and PROCR, which were considered potential key genes in CVTMBT. CVTMBT presents with enhancement and mass effect on magnetic resonance imaging, accompanied by various predisposing factors, shorter disease duration, and coagulation dysfunction. The nine key genes identified as potential key genes in the pathogenesis of CVTMBT may be potential biomarkers for accurate screening and appropriate treatment.
References
Masuhr F, Mehraein S, Einhäupl K, 2004, Cerebral venous and sinus thrombosis. J Neurol, 251: 11–23. https://doi.org/10.1007/s00415-004-0321-7
Bousser MG, Ferro JM, 2007, Cerebral venous thrombosis: An update. Lancet Neurol, 6: 162–170. https://doi.org/10.1016/s1474-4422(07)70029-7
Mullins ME, Grant PE, Wang B, et al., 2004, Parenchymal abnormalities associated with cerebral venous sinus thrombosis: Assessment with diffusion-weighted MR imaging. AJNR Am J Neuroradiol, 25: 1666–1675.
Bousser MG, Chiras J, Bories J, et al., 1985, Cerebral venous thrombosis-a review of 38 cases. Stroke, 16: 199–213. https://doi.org/10.1161/01.str.16.2.199
Coutinho JM, van den Berg R, Zuurbier SM, et al., 2014, Small juxtacortical hemorrhages in cerebral venous thrombosis. Ann Neurol, 75: 908–916. https://doi.org/10.1002/ana.24180
Mehraein S, Schmidtke K, Villringer A, et al., 2003, Heparin treatment in cerebral sinus and venous thrombosis: Patients at risk of fatal outcome. Cerebrovasc Dis, 15: 17–21. https://doi.org/10.1159/000067117
Yu Y, Ren M, Yao S, et al., 2016, Pathological confirmation of 4 cases with isolated cortical vein thrombosis previously misdiagnosed as brain tumor. Oncol Lett, 11: 649–653. https://doi.org/10.3892/ol.2015.3931
Tsai FY, Wang AM, Matovich VB, et al., 1995, MR staging of acute dural sinus thrombosis: Correlation with venous pressure measurements and implications for treatment and prognosis. AJNR Am J Neuroradiol, 16: 1021–1029.
Bianchi D, Maeder P, Bogousslavsky J, et al., 1998, Diagnosis of cerebral venous thrombosis with routine magnetic resonance: An update. Eur Neurol, 40: 179–190. https://doi.org/10.1159/000007978
Bousser MG, 2000, Cerebral venous thrombosis: Diagnosis and management. J Neurol, 247: 252–258. https://doi.org/10.1007/s004150050579
Masuoka J, Wakamiya T, Mineta T, et al., 2009, Thrombosis of the superior petrosal vein mimicking brain tumor. Case report. Neurol Med Chir (Tokyo), 49: 359–361. https://doi.org/10.2176/nmc.49.359
Lövblad KO, Bassetti C, Schneider J, et al., 2001, Diffusion-weighted MR in cerebral venous thrombosis. Cerebrovasc Dis, 11: 169–176. https://doi.org/10.1159/000047634
Gradinscak DJ, Fulham MJ, Besser M, et al., 2004, Post-traumatic cerebral venous infarct mimicking an infiltrative glioma. Clin Nucl Med, 29: 68–69. https://doi.org/10.1097/01.rlu.0000103233.31619.d1
Bakshi R, Lindsay BD, Bates VE, et al., 1998, Cerebral venous infarctions presenting as enhancing space-occupying lesions: MRI findings. J Neuroimaging, 8: 210–215. https://doi.org/10.1111/jon199884210
Xu T, Liang R, 2019, Cerebral venous thrombosis with tumor-like features: A case report and review of the literature. World Neurosurg, S1878-8750(18)32932-2. https://doi.org/10.1016/j.wneu.2018.12.109
Chang R, Friedman DP, 2004, Isolated cortical venous thrombosis presenting as subarachnoid hemorrhage: A report of three cases. AJNR Am J Neuroradiol, 25: 1676–1679.
Benabu Y, Mark L, Daniel S, et al., 2009, Cerebral venous thrombosis presenting with subarachnoid hemorrhage. Case report and review. Am J Emerg Med, 27: 96–106. https://doi.org/10.1016/j.ajem.2008.01.021
Xu S, Tang L, Li X, et al., 2020, Immunotherapy for glioma: Current management and future application. Cancer Lett, 476: 1–12. https://doi.org/10.1016/j.canlet.2020.02.002
Einhäupl K, Bousser MG, De Bruijn SF, et al., 2006, EFNS guideline on the treatment of cerebral venous and sinus thrombosis. Eur J Neurol, 13: 553–559. https://doi.org/10.1111/j.1468-1331.2006.01398.x
Bolger AM, Lohse M, Usadel B, 2014, Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics, 30: 2114–2120. https://doi.org/10.1093/bioinformatics/btu170
Pertea M, Pertea GM, Antonescu CM, et al., 2015, StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat Biotechnol, 33: 290–295. https://doi.org/10.1038/nbt.3122
Robinson MD, Mccarthy DJ, Smyth GK, 2010, edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics, 26: 139–140. https://doi.org/10.1093/bioinformatics/btp616
Wang W, Lin C, Hong J, et al., 2018, Effects of increased intracranial pressure gradient on cerebral venous infarction in rabbits. World Neurosurg, 120: e161–e168. https://doi.org/10.1016/j.wneu.2018.07.264
Duijn JH, Matson GB, Maudsley AA, et al., 1992, Human brain infarction: Proton MR spectroscopy. Radiology, 183: 711–718. https://doi.org/10.1148/radiology.183.3.1584925
Gideon P, Henriksen O, Sperling B, et al., 1992, Early time course of N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline in the brain after acute stroke. A proton magnetic resonance spectroscopy study. Stroke, 23: 1566–1572. https://doi.org/10.1161/01.str.23.11.1566
Smith E, Kumar V, 2018, BET 1: Does a normal D-dimer rule out cerebral venous sinus thrombosis (CVST)? Emerg Med J, 35: 396–397. https://doi.org/10.1136/emermed-2018-207777.1
Duan J, Leng X, Han Z, et al., 2021, Identifying biomarkers associated with venous infarction in acute/subacute cerebral venous thrombosis. Aging Dis, 12: 93–101. https://doi.org/10.14336/ad.2020.0405
Jacobs K, Moulin T, Bogousslavsky J, et al., 1996, The stroke syndrome of cortical vein thrombosis. Neurology, 47: 376–382. https://doi.org/10.1212/wnl.47.2.376
Harada Y, Hirata K, Kobayashi H, et al., 2012, A pitfall of C-11 methionine PET: Cerebral venous infarction mimicked a glioma. Clin Nucl Med, 37: 110–111. https://doi.org/10.1097/rlu.0b013e3182336433
Xu J, Peng G, Ouyang Y, 2019, A novel mutation Gly222Arg in PROS1 causing protein S deficiency in a patient with pulmonary embolism. J Clin Lab Anal, 34: e23111. https://doi.org/10.1002/jcla.23111
Seheult JN, Chibisov I, 2016, A case of unexplained cerebral sinus thrombosis in a 22-year-old obese Caucasian woman. Lab Med, 47: 233–240. https://doi.org/10.1093/labmed/lmw023
Merten M, Thiagarajan P, 2004, P-selectin in arterial thrombosis. Z Kardiol, 93: 855–863. https://doi.org/10.1007/s00392-004-0146-5
Gandrille S, 2008, Endothelial cell protein C receptor and the risk of venous thrombosis. Haematologica, 93: 812–816. https://doi.org/10.3324/haematol.13243
Wenger RH, Hameister H, Clemetson KJ, 1991, Human platelet basic protein/connective tissue activating peptide- III maps in a gene cluster on chromosome 4q12-q13 along with other genes of the beta-thromboglobulin superfamily. Hum Genet, 87: 367–368. https://doi.org/10.1007/bf00200921
Gemmati D, Vigliano M, Burini F, et al., 2016, Coagulation factor XIIIA (F13A1): Novel perspectives in treatment and pharmacogenetics. Curr Pharm Des, 22: 1449–1459. https://doi.org/10.2174/1381612822666151210122954
Spiroski I, Kedev S, Antov S, et al., 2009, Investigation of SERPINE1 genetic polymorphism in Macedonian patients with occlusive artery disease and deep vein thrombosis. Kardiol Pol, 67: 1088–1094.
Blann AD, Nadar SK, Lip GY, 2003, The adhesion molecule P-selectin and cardiovascular disease. Eur Heart J, 24: 2166–2179. https://doi.org/10.1016/j.ehj.2003.08.021
Quintero-Ronderos P, Mercier E, Gris JC, et al., 2017, THBD sequence variants potentially related to recurrent pregnancy loss. Reprod Biol Endocrinol, 15: 92. https://doi.org/10.1186/s12958-017-0311-0
Komsa-Penkova R, Golemanov G, Tsankov B, et al., 2017, Rs5918ITGB3 polymorphism, smoking, and BMI as risk factors for early onset and recurrence of DVT in young women. Clin Appl Thromb Hemost, 23: 585–595. https://doi.org/10.1177/1076029615624778
Gierula M, Ahnström J, 2020, Anticoagulant protein S-New insights on interactions and functions. J Thromb Haemost, 18: 2801–2811. https://doi.org/10.1111/jth.15025
Dennis J, Kassam I, Morange PE, et al., 2015, Genetic determinants of tissue factor pathway inhibitor plasma levels. Thromb Haemost, 114: 245–257. https://doi.org/10.1160/th14-12-1043
Wang ZH, Zhao ZJ, Xu K, et al., 2015, Hereditary protein S deficiency leads to ischemic stroke. Mol Med Rep, 12: 3279–3284. https://doi.org/10.3892/mmr.2015.3793
Wismans LV, Lopuhaä B, De Koning W, et al., 2022, Increase of mast cells in COVID-19 pneumonia may contribute to pulmonary fibrosis and thrombosis. Histopathology. Epub ahead of print. https://doi.org/10.1111/his.14838
Horioka K, Tanaka H, Isozaki S, et al., 2019, Hypothermia-induced activation of the splenic platelet pool as a risk factor for thrombotic disease in a mouse model. J Thromb Haemost, 17: 1762–1771. https://doi.org/10.1111/jth.14555
Reiner AP, Carty CL, Jenny NS, et al., 2008, PROC, PROCR and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: The Cardiovascular Health Study. J Thromb Haemost, 6: 1625–1632. https://doi.org/10.1111/j.1538-7836.2008.03118.x
Stacey D, Chen L, Stanczyk PJ, et al., 2022, Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus. Nat Commun, 13: 1222. https://doi.org/10.1038/s41467-022-28729-3
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