Abstract
Despite the prognostic value of IDH and other gene mutations found in diffuse glioma, markers that judge individual prognosis of patients with diffuse lower‐grade glioma (LGG) are still lacking. This study aims to develop an expression‐based microRNA signature to provide survival and radiotherapeutic response prediction for LGG patients. MicroRNA expression profiles and relevant clinical information of LGG patients were downloaded from The Cancer Genome Atlas (TCGA; the training group) and the Chinese Glioma Genome Atlas (CGGA; the test group). Cox regression analysis, random survival forests‐variable hunting (RSFVH) screening and receiver operating characteristic (ROC) were used to identify the prognostic microRNA signature. ROC and TimeROC curves were plotted to compare the predictive ability of IDH mutation and the signature. Stratification analysis was conducted in patients with radiotherapy information. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore the biological function of the signature. We identified a five‐microRNA signature that can classify patients into low‐risk or high‐risk group with significantly different survival in the training and test datasets (P < 0.001). The five‐microRNA signature was proved to be superior to IDH mutation in survival prediction (AUCtraining = 0.688 vs 0.607). Stratification analysis found the signature could further divide patients after radiotherapy into two risk groups. GO and KEGG analyses revealed that microRNAs from the prognostic signature were mainly enriched in cancer‐associated pathways. The newly discovered five‐microRNA signature could predict survival and radiotherapeutic response of LGG patients based on individual microRNA expression.
Highlights
Glioma is a common type of intracranial malignant tumour, characterized by diffuse infiltration, no clear boundary, infinite proliferation and high invasion
Isocitrate dehydrogenase (IDH) mutation and 1p/19g codeletion still have some defects in the prognosis evaluation and treatment guidance of patients with lower-grade gliomas (LGG)
This study analysed 624 LGG patients and found a good indicator for prognosis prediction and radiotherapy guidance, which is named as a five-microRNA signature
Summary
Glioma is a common type of intracranial malignant tumour, characterized by diffuse infiltration, no clear boundary, infinite proliferation and high invasion. Even after maximal resection plus post-operative chemoradiotherapy, the median survival of patients with glioblastoma is as short as about one year.[2] Gliomas of grades II and III are intermediate in terms of malignant degree and prognosis and are combined into lower-grade gliomas because of their similarity in high invasiveness and the tendency to recur or develop advanced lesions such as secondary glioblastoma. For patients with LGG, prognostic markers that can predict individual clinical outcome and treatment response are essential. MicroRNA could be used to predict treatment response and prognosis of many types of cancer and become a molecular marker. MicroRNA signature containing multiple microRNAs has been demonstrated its promising prognostic role in various tumours including breast cancer,[7] hepatocellular carcinoma[8] and glioblastoma.[9] there is a lack of microRNA signature that can predict individual outcomes of patients with LGG. 89 expression data and clinical data to identify a prognostic microRNA signature and validate its predictive ability for survival and treatment response
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