title: Testin (TES) as a candidate tumour suppressor and prognostic marker in human astrocytoma.
abstract: Astrocytomas are one of the most common brain tumours; however, the current methods used to characterize these tumours are inadequate. The establishment of molecular markers may identify variables required to improve tumour characterization and subtyping, and may aid to specify targets for improved treatment with essential prognostic value for patient survival. One such candidate is testin (TES), which was reported to have prognostic value for glioblastoma patients. However, the role of TES protein in gliomagenesis is currently unknown. In the present study, the methylation status of theTESpromoter was investigated in post-operative astrocytoma tumours of different malignancy grade, and its association with the survival of astrocytoma patients was evaluated. In addition, the expression of TES protein was investigated in the same set of astrocytoma tumours tissue, and the association of protein expression with glioma patients survival was evaluated. The methylation status ofTESwas assessed by methylation-specific polymerase chain reaction in 138 different grade astrocytoma samples. Western blot analysis was used to characterize the expression pattern ofTESin 86 different grade astrocytoma specimens: 13 of pathological grade I, 31 of pathological grade II, 17 of pathological grade III and 25 of pathological grade IV (glioblastoma). Statistical analyses were conducted to investigate the association between tumour molecular pattern, patient clinical variables and overall survival. The methylation analysis of theTESpromoter exhibited a distinct profile between astrocytomas of different malignancy grade (P<0.001). Furthermore, gene promoter methylation was significantly associated with patients' age, survival and pathological grade (P<0.001). The protein expression level of TES was significantly lower in glioblastoma (grade IV astrocytoma) than in lower grade (II-III) astrocytoma tissue (P=0.028 and P=0.04, respectively). Additionally, short overall survival of patients was markedly associated with low TES protein expression (P=0.007). However, no association between TES methylation and TES protein expression was noticed. The present study demonstrated that decreased expression of TES may be important in tumour progression and prognosis in human astrocytomas. TES may be a useful marker for predicting the clinical outcome of astrocytoma patients.
authors.affiliation: Laboratory of Neuro-Oncology and Genetics, Neuroscience Institute, Lithuanian University of Health Sciences, LT-50009 Kaunas, Lithuania.
authors.forename: Giedrius
authors.initials: G
authors.lastname: Steponaitis
authors.affiliation: Laboratory of Neuro-Oncology and Genetics, Neuroscience Institute, Lithuanian University of Health Sciences, LT-50009 Kaunas, Lithuania.
authors.forename: Arunas
authors.initials: A
authors.lastname: Kazlauskas
authors.affiliation: Laboratory of Neuro-Oncology and Genetics, Neuroscience Institute, Lithuanian University of Health Sciences, LT-50009 Kaunas, Lithuania.
authors.forename: Daina
authors.initials: D
authors.lastname: Skiriute
authors.affiliation: Laboratory of Neuro-Oncology and Genetics, Neuroscience Institute, Lithuanian University of Health Sciences, LT-50009 Kaunas, Lithuania.
authors.forename: Indre
authors.initials: I
authors.lastname: Valiulyte
authors.affiliation: Laboratory of Neuro-Oncology and Genetics, Neuroscience Institute, Lithuanian University of Health Sciences, LT-50009 Kaunas, Lithuania.
authors.forename: Kestutis
authors.initials: K
authors.lastname: Skauminas
authors.affiliation: Laboratory of Neuro-Oncology and Genetics, Neuroscience Institute, Lithuanian University of Health Sciences, LT-50009 Kaunas, Lithuania.
authors.forename: Arimantas
authors.initials: A
authors.lastname: Tamasauskas
authors.affiliation: Laboratory of Neuro-Oncology and Genetics, Neuroscience Institute, Lithuanian University of Health Sciences, LT-50009 Kaunas, Lithuania.
authors.forename: Paulina
authors.initials: P
authors.lastname: Vaitkiene
keywords: DNA methylation; astrocytoma; expression; glioblastoma; glioma; survival; testin; testin LIM domain protein; testis-derived transcript