Dataset Information

Autophagy Gene Panel-Based Prognostic Model in Myelodysplastic Syndrome.

ABSTRACT: Abnormal autophagy is related to the pathogenesis and clinical symptoms of myelodysplastic syndrome (MDS). However, the effect of autophagy-related genes (ARGs) on the prognosis of MDS remains unclear. Here, we examined the expression profile of 108 patients with MDS from the GSE58831 dataset, and identified 22 genes that were significantly associated with overall survival. Among them, seven ARGs were screened and APIs were calculated for all samples based on the expression of the seven ARGs, and then, MDS patients were categorized into high- and low-risk groups based on the median APIs. The overall survival of patients with high-risk scores based on these seven ARGs was shorter than patients with low-risk scores in both the training cohort (P = 2.851e-06) and the validation cohort (P = 9.265e-03). Additionally, API showed an independent prognostic indicator for survival in the training samples [hazard ratio (HR) = 1.322, 95% confidence interval (CI): 1.158-1.51; P < 0.001] and the validation cohort (HR = 1.05, 95% CI: 1-1.1; P < 0.01). The area under the receiver operating characteristic curve (AUROC) of API and IPSS were 43.0137 and 66.0274 in the training cohorts and the AUC of the validation cohorts were 41.5361 and 72.0219. Our data indicate these seven ARGs can predict prognosis in patients with MDS and could guide individualized treatment.

SUBMITTER: Wang MJ

PROVIDER: S-EPMC7894207 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Autophagy Gene Panel-Based Prognostic Model in Myelodysplastic Syndrome.

Wang Ming-Jing MJ Liu Wei-Yi WY Wang Xue-Ying XY Li Yu-Meng YM Xiao Hai-Yan HY Quan Ri-Cheng RC Huang Gang G Hu Xiao-Mei XM

Frontiers in oncology 20210205

Abnormal autophagy is related to the pathogenesis and clinical symptoms of myelodysplastic syndrome (MDS). However, the effect of autophagy-related genes (ARGs) on the prognosis of MDS remains unclear. Here, we examined the expression profile of 108 patients with MDS from the GSE58831 dataset, and identified 22 genes that were significantly associated with overall survival. Among them, seven ARGs were screened and APIs were calculated for all samples based on the expression of the seven ARGs, an ...[more]

PMID: 33614490

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Project description:Genetic mutations drive the pathogenesis of the myelodysplastic syndrome (MDS) and are closely associated with clinical phenotype. Therefore, genetic mutations may predict clinical outcomes after allogeneic hematopoietic stem-cell transplantation.We performed targeted mutational analysis on samples obtained before transplantation from 1514 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research Repository between 2005 and 2014. We evaluated the association of mutations with transplantation outcomes, including overall survival, relapse, and death without relapse.TP53 mutations were present in 19% of the patients and were associated with shorter survival and a shorter time to relapse than was the absence of TP53 mutations, after adjustment for significant clinical variables (P<0.001 for both comparisons). Among patients 40 years of age or older who did not have TP53 mutations, the presence of RAS pathway mutations was associated with shorter survival than was the absence of RAS pathway mutations (P=0.004), owing to a high risk of relapse, and the presence of JAK2 mutations was associated with shorter survival than was the absence of JAK2 mutations (P=0.001), owing to a high risk of death without relapse. The adverse prognostic effect of TP53 mutations was similar in patients who received reduced-intensity conditioning regimens and those who received myeloablative conditioning regimens. By contrast, the adverse effect of RAS pathway mutations on the risk of relapse, as compared with the absence of RAS pathway mutations, was evident only with reduced-intensity conditioning (P<0.001). In young adults, 4% of the patients had compound heterozygous mutations in the Shwachman-Diamond syndrome-associated SBDS gene with concurrent TP53 mutations and a poor prognosis. Mutations in the p53 regulator PPM1D were more common among patients with therapy-related MDS than those with primary MDS (15% vs. 3%, P<0.001).Genetic profiling revealed that molecular subgroups of patients undergoing allogeneic hematopoietic stem-cell transplantation for MDS may inform prognostic stratification and the selection of conditioning regimen. (Funded by the Edward P. Evans Foundation and others.).

Dataset Information

Autophagy Gene Panel-Based Prognostic Model in Myelodysplastic Syndrome.

Publications

Autophagy Gene Panel-Based Prognostic Model in Myelodysplastic Syndrome.

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