Aging-related tumor associated fibroblasts changes could worsen the prognosis of GBM patients
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Cancer Cell International Open Access
PRIMARY RESEARCH
Aging‑related tumor associated fibroblasts changes could worsen the prognosis of GBM patients Hongwang Song1*†, Xiaojun Fu2*† , Chenxing Wu2 and Shouwei Li2
Abstract Background: Glioblastoma multiforme (GBM) is the most malignant tumor in human brain, with highly heterogeneity among different patients. Age could function as an incidence and prognosis risk factor for many tumors. Method: A series of bioinformatic experiments were conducted to evaluate the differences of incidence, differential expressed genes, enriched pathways with the data from Surveillance, Epidemiology, and End Results (SEER) program, the cancer genome atlas (TCGA) and Chinese glioma genome atlas (CGGA) project. Results: We discovered in our present study that distinct difference of incidence and prognosis of different aged GBM patients. By a series of bioinformatic method, we found that the tumor associated fibroblasts (TAFs) was the most crucial tumor microenvironment (TME) component that led to this phenomenon. Epithelial-mesenchymal transition (EMT) could be the mechanism by which TAFs regulate the progression of GBM. Conclusion: We have proposed a close correlation between age and GBM incidence and prognosis, and propose the underlying mechanism behind this correlation by mining different databases, which laid the foundation for future research. Keywords: Glioblastoma, Tumor heterogeneity, Tumor microenvironment, Tumor associated fibroblasts, Epithelial mesenchymal transition
Backgrounds Glioblastoma multiforme (GBM) is the most malignant and frequently occurring type of primary tumor in central nervous system, which accounts for more than 60% of all brain tumors in adults [1, 2]. The current treatment of GBM relies on surgical resection of gross tumor followed by radio-chemotherapy, as well as adjuvant therapy with temozolomide. Despite such variety of therapies against it, GBM is still a deadly disease with extremely poor *Correspondence: [email protected]; [email protected] † Hongwang Song and Xiaojun Fu contribute equally to this work 1 Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, China 2 Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Xiangshanyikesong 50#, HaiDian District, Beijing 100093, China
prognosis [1, 3]. GBM patients have a median survival of approximately 14 to 15 months after the diagnosis [4]. However, although the overall prognosis of GBM patients is very poor, there is still a significant prognostic diversity among these patients. This diversity is largely due to the heterogeneity of GBM. Tumor heterogeneity, characterized by distinct cellular or genetic alterations that occur in individual tumors originating in the same sources, as well as nonneoplasm cells involved in the initiating and progression of tumors, is one of the most important hallmarks of GBM [5, 6]. Tumor heterogeneity includes intratumoral heterogeneity [7, 8] and intercellular heterogeneity [9]. The hetero
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