Patients’ Derived Short-Term Glioma Culture: Identification of Aggressive, Drug-Resistant Phenotype

Abstract

Background: Low-grade gliomas are mostly played down as less fatal malignancy despite the fact that most of them eventually progress to high grade thereby leading to death. In vitro glioma cultures have been emerged as a standard model to get insight into phenotypic transformation, drug response and tumor relapse. In this study, attempt was made to establish comprehensive patient-specific short-term cultures comprising of both low-grade and high-grade malignant glioma.Methods: 50 patients with MRI diagnosed malignant glioma were recruited for this study. Fresh surgical tumor tissues were used for the establishment of primary culture. Patients' samples were analyzed for the presence of IDH1/2 mutations, 1p/19q co-deletion, MIB1 and p53. Established primary glioma culture were evaluated for proliferation rate, sensitivity to temozolomide and expression pattern of Glial-Mesenchymal Transition (GMT) markers. Results: Short-term glioma cultures were successfully established in 40 clinical samples. Glioma cultures, irrespective of tumor grades, displayed two distinct pattern of growth kinetics -one with shorter doubling time (high-proliferating) and another group with longer doubling time (lowproliferating). Significant distinctive features were noticed between these two groups in terms of response to temozolomide, expression pattern of GMT markers and their association with clinical/pathological features of malignant glioma. Conclusion: Our findings effectively demonstrated the practicality of development of short-term glioma culture model toward a functional approach for personalized medicine. Our model further revealed the presence of highly proliferative, drug-resistant phenotype among low-grade gliomas. Hence, short-term culture model could be an important prognostic tool to predict patient clinical responses and also provide cue about imminent tumour relapse.