Abstract 444: MACC1 as biomarker for progression and prognosis of human malignant glioma

Abstract

Abstract Metastasis-associated in colon cancer-1 (MACC1) is a prognostic indicator for metastasis formation and metastasis-free survival of colon cancer patients. Patients with low MACC1 expressing primary tumors had a 5-year-survival of 80%, whereas subjects with high MACC1 expressing tumors had a 5-year-survival of only 15%. Correlations of MACC1 expression levels with tumor progression, recurrence and metastasis have meanwhile been reported for e.g. gastric, lung and hepatocellular cancer. However, no data are available concerning MACC1 expression in human astrocytic tumors. Glioblastoma multiforme (GBM) are the most prevalent brain tumors of adults either developing de novo without known precursor-lesion (primary GBM), or progressing from low grade astrocytomas (secondary GBM). Patients suffering from GBM have a very disadvantageous prognosis. Although these tumors rarely metastasize, they are characterized by rapid growth, and their invasive and migratory behavior is similar to those of metastatic cells of tumors with different origin. Therefore we tested our hypothesis on MACC1 involvement in progression of human gliomas. MACC1 mRNA expression increased concomitantly with increasing WHO grading, as demonstrated by semi-quantitative and quantitative RT-PCR of biopsies from human low grade astrocytomas and GBM. MACC1 protein expression allowed discrimination of dormant and recurrent LGA and of primary and secondary GBM, as shown by immunohistochemistry of an independent patients’ cohort. Furthermore, strong MACC1 expression was associated with reduced median patients’ survival. Finally, we performed real-time measurements of migration and proliferation in the MACC1-transfected GBM cell line U138/MACC1 and found promoted proliferation and migration. Therefore, MACC1 may be a new biomarker for progression and for prognosis of human malignant gliomas and might represent a new potential therapeutic target for inhibition of their proliferation and migration. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 444. doi:1538-7445.AM2012-444