Abstract
Glioblastoma multiforme (GBM) is the most common and deadliest primary brain tumor, driving patients to death within 15 months after diagnosis (short term survivors, ST), with the exception of a small fraction of patients (long term survivors, LT) surviving longer than 36 months. Here we present deep sequencing data showing that peritumoral (P) areas differ from healthy white matter, but share with their respective frankly tumoral (C) samples, a number of mRNAs and microRNAs representative of extracellular matrix remodeling, TGFβ and signaling, of the involvement of cell types different from tumor cells but contributing to tumor growth, such as microglia or reactive astrocytes. Moreover, we provide evidence about RNAs differentially expressed in ST vs LT samples, suggesting the contribution of TGF-β signaling in this distinction too. We also show that the edited form of miR-376c-3p is reduced in C vs P samples and in ST tumors compared to LT ones. As a whole, our study provides new insights into the still puzzling distinction between ST and LT tumors, and sheds new light onto that "grey" zone represented by the area surrounding the tumor, which we show to be characterized by the expression of several molecules shared with the proper tumor mass.
Highlights
Glioblastoma multiforme (GBM; World Health Organization [WHO] grade IV) is the most common and most malignant primary tumor of the brain
We report a broad analysis of central tumor samples, from both long term survivors (LT) and short term ones (ST), integrated by the same analysis performed on peritumoral areas from the same patients
We collected frankly tumoral areas (C) as well as peritumoral areas from 4 long term (LT: survival longer than 36 months) and 9 short term (ST: survival shorter than 36 months) patients diagnosed with primary glioblastoma (Table 1a)
Summary
Glioblastoma multiforme (GBM; World Health Organization [WHO] grade IV) is the most common and most malignant primary tumor of the brain. Diffuse infiltration into surrounding brain tissue and suppression of antitumor immune surveillance contribute to the malignant phenotype of glioblastomas. The prognosis of GBM patients is poor and the median survival time after diagnosis is still in the range of just 12 months [1], or even shorter [2]. An interesting exception to this rule is a small fraction (less than 10%) of GBM patients, referred to as long-term survivors (LTS), who survive longer than 36 months. We are still far from the comprehension of the reasons leading a glioblastoma patient to survive significantly longer than another one
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