Differential expression of STMN family genes in low-grade astrocytomas relative to oligodendroglioma

• Grant number: 14/03495-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2014
• Effective date (End): December 31, 2014
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Suely Kazue Nagahashi Marie
• Grantee: Rodrigo Akira Watanabe
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Gliomas, originating from glial cells, are the most frequent central nervous system tumors, including astrocytomas, and oligodendrogliomas. According to World Health Organization, astrocytomas are classified into four grades of malignancy (I to IV), and oligodendrogliomas into two grades (II and III). Additionally, there are mixed tumors, oligoastrocytomas. This classification is based on morphological aspects, and the differentiation between low-grade astrocytomas and oligodendrogliomas lacks precision. This difficulty impacts prognostic and therapeutic issues, as median recurrence, malignant progression, and overall survival time range from 2 to 5 years among astrocytomas, and 5 to 10 years among oligodendrogliomas. The objective of the present study is to select and analyze molecular markers to better differentiate low-grade astrocytoma from oligodendroglioma. To this end, preliminary analysis of oligonucleotide microarrays of both types of glioma already available in the Molecular and Cellular Laboratory have been carried out. The gene stathmin 3 (STMN3) has been detected as differentially expressed between these two types of tumors. Subsequent analysis of the STMN3 interactome has demonstrated its connectivity to the other three members of the stathmin family (STMN1, STMN2, and STMN4). Therefore, as specific aims, experiments will be performed: 1) to analyze the expression of the four members of the stathmin family in a series of astrocytomas of different grades (23 grade I, 23 grade II, 18 grade III, and 87 grade IV) and oligodendrogliomas (13 grade II and 10 grade III) in comparison to 28 non-neoplastic brain tissue; 2) to analyze their differential expressions between astrocytoma and oligodendroglioma, and in malignant progression, and 3) to correlate with clinical data, including recurrence, malignant progression, and overall survival time. The gene expression will be determined by quantitative PCR by SyberGreen, normalized by three reference genes. For statistical analysis, Kruskal Wallis´ test will be used for paired gene expression comparison; Dunn´s test for multivariate comparisons; Pearson´s or Spearman's test for two by two gene expression correlation; Kaplan Meier´s test for overall survival analyses. The date distribution will be calculated by the Kolmogorov Smirnov test. The working hypothesis is that STMN3 and/or other members of the stathmin family are molecular markers to differentiate low-grade astrocytoma and oligodendroglioma, and a predictive marker for malignant tumor progression, with impact on clinical outcome. (AU)