以四個長鏈非編碼核醣核酸組成之評分系統預測骨髓化生不良症候群病患之預後

A 4-lncRNA Scoring System for Prognostication in Adult Myelodysplastic Syndromes

姚啟元(Chi-Yuan Yao)

指導教授 ： 田蕙芬

共同指導教授 ： 周文堅

國立臺灣大學/醫學院/臨床醫學研究所/碩士(2017年)

https://doi.org/10.6342/NTU201702922

摘要

無資料

關鍵字

長鏈非編碼RNA ； 骨髓化生不良症候群 ； 基因突變 ； 預後

並列摘要

Long noncoding RNAs (lncRNAs) not only participate in normal hematopoiesis but also contribute to the pathogenesis of acute leukemia. However, their clinical and prognostic relevance in myelodysplastic syndromes (MDS) remains unclear to date. In this study, we profiled the lncRNA expressions in 176 adult patients with primary MDS, and identified four lncRNAs whose expression levels were significantly associated with overall survival (OS). We then constructed a risk scoring system with the weighted sum of these four lncRNAs. Higher lncRNA scores were associated with higher marrow blast percentages, higher-risk subtypes of MDS based on both the Revised International Prognostic Scoring System (IPSS-R) and WHO classification, complex cytogenetic changes, and mutations in RUNX1, ASXL1, TP53, SRSF2 and ZRSR2, while inversely correlated with SF3B1 mutation. Patients with higher lncRNA scores had a significantly shorter OS and a higher five-year leukemic transformation rate compared with those with lower scores. The prognostic significance of our 4-lncRNA risk score could be validated in an independent MDS cohort. In multivariate analysis, higher lncRNA scores remained an independent unfavorable risk factor for OS (RR 4.783, 95% CI 2.491-9.182, P<0.001) irrespective of age, cytogenetics, IPSS-R and gene mutations. To our knowledge, this is the first report to provide a lncRNA platform for risk stratification of MDS patients. In conclusion, our integrated 4-lncRNA risk scoring system is correlated with distinctive clinical and biological features in MDS patients, and serves as an independent prognostic factor for overall survival and leukemic transformation. This concise yet powerful lncRNA-based scoring system can help improve the current risk stratification of MDS patients.

並列關鍵字

Long non-coding RNA ； myelodysplastic syndromes ； gene mutation ； prognosis

參考文獻

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