Dataset Information

Dissecting and analyzing the Subclonal Mutations Associated with Poor Prognosis in Diffuse Glioma.

ABSTRACT: The prognostic and therapeutic implications in diffuse gliomas are still challenging. In this study, we first performed an integrative framework to infer the clonal status of mutations in glioblastomas (GBMs) and low-grade gliomas (LGGs) by using exome sequencing data from TCGA and observed both clonal and subclonal mutations for most mutant genes. Based on the clonal status of a given gene, we systematically investigated its prognostic value in GBM and LGG, respectively. Focusing on the subclonal mutations, our results showed that they were more likely to contribute to the poor prognosis, which could be hardly figured out without considering clonal status. These risk subclonal mutations were associated with some specific genomic features, such as genomic instability and intratumor heterogeneity, and their accumulation could enhance the prognostic value. By analyzing the regulatory mechanisms underlying the risk subclonal mutations, we found that the subclonal mutations of AHNAK and AHNAK2 in GBM and those of NF1 and PTEN in LGG could influence some important molecules and functions associated with glioma progression. Furthermore, we dissected the role of risk subclonal mutations in tumor evolution and found that advanced subclonal mutations showed poorer overall survival. Our study revealed the importance of clonal status in prognosis analysis, highlighting the role of the subclonal mutation in glioma prognosis.

SUBMITTER: Bai M

PROVIDER: S-EPMC9039777 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Dissecting and analyzing the Subclonal Mutations Associated with Poor Prognosis in Diffuse Glioma.

Bai Ming M Wang Xiaolong X Zhang Huixue H Wang Jianjian J Lyaysan Gaysina G Xu Si S Tian Kuo K Wang Tianfeng T Li Jie J Wang Na N Lu Xiaoyu X Zhang Xiaoming X Wang Lihua L

BioMed research international 20220418

The prognostic and therapeutic implications in diffuse gliomas are still challenging. In this study, we first performed an integrative framework to infer the clonal status of mutations in glioblastomas (GBMs) and low-grade gliomas (LGGs) by using exome sequencing data from TCGA and observed both clonal and subclonal mutations for most mutant genes. Based on the clonal status of a given gene, we systematically investigated its prognostic value in GBM and LGG, respectively. Focusing on the subclon ...[more]

PMID: 35496054

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Project description:Purpose: Glioma is the most common malignant brain tumor. The molecular mechanisms underlying its malignancy are not fully understood. LAMC1, which encodes extracellular matrix protein laminin ?1, has been implicated in some malignant tumors but has not been systematically evaluated in glioma. The aim of this study was to evaluate the expression of LAMC1 and its clinical significance. Patients and methods: LAMC1 protein expression in 52 fresh-frozen specimens of different pathological grade gliomas and 5 normal brain tissues was detected by Western blotting. Immunohistochemistry was used to detect LAMC1 protein expression in another set of 76 glioma tissues and 8 normal brain tissues. The associations between clinicopathological factors and LAMC1 expression were analyzed. A log-rank test and a multivariate Cox proportional hazards model were used to determine the relationship between LAMC1 expression and patient prognosis. The expression of LAMC1 at the mRNA level was analyzed in the TCGA database. Results: LAMC1 was highly expressed in high-grade glioma tissues, with moderate expression in low-grade gliomas, and weak or no expression in normal brain tissues, as detected by Western blotting and immunohistochemistry. A chi-square test indicated that LAMC1 expression was associated with pathological grade but not with other clinicopathological factors, such as age, sex, and tumor size. LAMC1 expression at the mRNA level was upregulated in high-grade gliomas compared with low-grade gliomas and normal brain tissue in the TCGA database. The Kaplan-Meier plot and log-rank test in our patient series showed that high LAMC1 expression was significantly associated with shorter survival, which was consistent with the TCGA database analysis. A multivariate Cox proportional hazards model revealed that LAMC1 expression, WHO grade, and surgery procedure were significantly correlated with overall survival and progression-free survival. Conclusion: These results demonstrated that LAMC1 may play an important role in glioma progression and may be used in the diagnosis, prognosis, and targeted therapy of glioma patients.

Dataset Information

Dissecting and analyzing the Subclonal Mutations Associated with Poor Prognosis in Diffuse Glioma.

Publications

Dissecting and analyzing the Subclonal Mutations Associated with Poor Prognosis in Diffuse Glioma.

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