Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Aug 16;1(19):1505-1516.
doi: 10.1182/bloodadvances.2017008284. eCollection 2017 Aug 22.

A 4-lncRNA scoring system for prognostication of adult myelodysplastic syndromes

Chi-Yuan Yao  1   2   3 , Ching-Hsuan Chen  4 , Huai-Hsuan Huang  1 , Hsin-An Hou  1 , Chien-Chin Lin  1   2   3 , Mei-Hsuan Tseng  1 , Chein-Jun Kao  1 , Tzu-Pin Lu  4 , Wen-Chien Chou  1   2 , Hwei-Fang Tien  1
Affiliations

A 4-lncRNA scoring system for prognostication of adult myelodysplastic syndromes

Chi-Yuan Yao et al. Blood Adv. .

Abstract

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 (MDSs) remains unclear to date. In this study, we profiled lncRNA expressions in 176 adult patients with primary MDS, and identified 4 lncRNAs whose expression levels were significantly associated with overall survival (OS). We then constructed a risk-scoring system with the weighted sum of these 4 lncRNAs. Higher lncRNA scores were associated with higher marrow blast percentages, higher-risk subtypes of MDSs (based on both the Revised International Prognostic Scoring System [IPSS-R] and World Health Organization classification), complex cytogenetic changes, and mutations in RUNX1, ASXL1, TP53, SRSF2, and ZRSR2, whereas they were inversely correlated with SF3B1 mutation. Patients with higher lncRNA scores had a significantly shorter OS and a higher 5-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 (relative risk, 4.783; P < .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 survival and leukemic transformation. This concise yet powerful lncRNA-based scoring system holds the potential to improve the current risk stratification of MDS patients.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Circos diagrams illustrating the different comutation patterns. Panels A and B depict the co-occurrence of mutations in patients with higher vs lower lncRNA scores, respectively. Ribbon widths are proportional to the frequencies of mutation co-occurrence.
Figure 2.
Figure 2.
Kaplan-Meier plots, stratified by lncRNA scores. (A) OS and (B) cumulative incidence of AML transformation of the 176 MDS patients in the training cohort. Patients with higher lncRNA scores had worse clinical outcomes than those with lower scores.
Figure 3.
Figure 3.
Kaplan-Meier plots, stratified by the integration of IPSS-R and lncRNA scores. (A) OS and (B) cumulative incidence of AML transformation of the 164 patients in the training cohort who had cytogenetic data at diagnosis (thus IRSS-R could be calculated). The incorporation of the lncRNA scoring system into the traditional IPSS-R classification could refine risk stratification of MDS patients.
Figure 4.
Figure 4.
Kaplan-Meier plots of an independent validation cohort stratified by lncRNA scores. (A) OS and (B) cumulative incidence of AML transformation of the 30 MDS patients in the validation cohort.. Patients with higher lncRNA scores had shorter OS and higher AML transformation rates.
Figure 5.
Figure 5.
Heatmap demonstrating differential gene expression. Depicted are the 255 genes that are differentially expressed between patients with the highest (> average +1 SD, n = 22) and the lowest (< average − 1 SD, n = 22) lncRNA risk scores.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Tefferi A, Vardiman JW. Myelodysplastic syndromes. N Engl J Med. 2009;361(19):1872-1885. - PubMed
    1. Adès L, Itzykson R, Fenaux P. Myelodysplastic syndromes. Lancet. 2014;383(9936):2239-2252. - PubMed
    1. Greenberg P, Cox C, LeBeau MM, et al. . International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079-2088. - PubMed
    1. Greenberg PL, Tuechler H, Schanz J, et al. . Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454-2465. - PMC - PubMed
    1. Stone RM. How I treat patients with myelodysplastic syndromes. Blood. 2009;113(25):6296-6303. - PubMed
-