title: 5-hydroxymethylcytosine loss is associated with poor prognosis for patients with WHO grade II diffuse astrocytomas.
abstract: Currently, the reliable prognostic biomarkers for WHO grade II diffuse astrocytomas (DA) are still limited. We investigated the relations between the level of 5-Hydroxymethylcytosine (5hmC), an oxidated production of 5-methylcytosine (5mC) by the ten eleven translocated (TET) enzymes, and clinicopathological features of glioma patients. With an identified anti-5hmC antibody, we performed immunohistochemistry in 287 glioma cases. We detected that 5hmC variably reduced in most gliomas and 5hmC reduction was closely associated with higher pathological grades and shortened survival of glioma patients. In multivariate analysis, 5hmC had no independent prognostic value in the entire patient cohort. However, multivariate analysis within subtypes of gliomas revealed that 5hmC was still a prognostic marker confined to DA. In addition, we detected that IDH1 mutation by DNA sequencing was associated with favorable survival within DA. Lastly, we detected that the combination of 5hmC/KI67 was a useful prognostic marker for restratification of DA.
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Feng
authors: F
authors: Zhang
authors: State Key Laboratory of Molecular Biology, Shanghai Key laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors: Yifan
authors: Y
authors: Liu
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Zhiwen
authors: Z
authors: Zhang
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Jie
authors: J
authors: Li
authors: Department of Health Statistics, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Yi
authors: Y
authors: Wan
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Liying
authors: L
authors: Zhang
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Yangmei
authors: Y
authors: Wang
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Xia
authors: X
authors: Li
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Yuqiao
authors: Y
authors: Xu
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Xin
authors: X
authors: Fu
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Xiumin
authors: X
authors: Zhang
authors: Company 13, Student Brigade, Fourth Military Medical University, Xi'an, 710032, China.
authors: Ming
authors: M
authors: Zhang
authors: Company 13, Student Brigade, Fourth Military Medical University, Xi'an, 710032, China.
authors: Zhekai
authors: Z
authors: Zhang
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Jing
authors: J
authors: Zhang
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Qingguo
authors: Q
authors: Yan
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Jing
authors: J
authors: Ye
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Zhe
authors: Z
authors: Wang
authors: State Key Laboratory of Molecular Biology, Shanghai Key laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors: Charlie Degui
authors: CD
authors: Chen
authors: Department of Neurosurgery; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Wei
authors: W
authors: Lin
authors: State Key Laboratory of Cancer Biology, Department of Pathology; Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Qing
authors: Q
authors: Li
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000737:chemistry; D001254:Astrocytoma / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D011379:Prognosis; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human