LINC00649 underexpression is an adverse prognostic marker in acute myeloid leukemia

BACKGROUND: Long noncoding RNAs (lncRNA) play a role in leukemogenesis, maintenance, development, and therapeutic resistance of AML. While few studies have focused on the prognostic significance of LINC00649 in AML, which we aim to investigate in this present study.

METHODS: We compared the expression level of LINC00649 between AML patients and healthy controls. The Kaplan-Meier curves of AML patients expressing high versus low level of LINC00649 was performed. The LINC00649 correlated genes/miRNAs/lncRNAs and methylation CpG sites were screened by Pearson correlation analysis with R (version 3.6.0), using TCGA-LAML database. The LINC00649 associated ceRNA network was established using lncBase 2.0 and miRWalk 2.0 online tools, combining results from correlation analysis. Finally, a prediction model was constructed using LASSO-Cox regression.

RESULTS: LINC00649 was underexpressed in bone marrow of AML group than that in healthy control group. The patients of LINC00649-low group have significantly inferior PFS and OS. A total of 154 mRNAs, 31 miRNAs, 28 lncRNAs and 1590 methylated CpG sites were identified to be significantly correlated with LINC00649. Furthermore, the network of ceRNA was established with 6 miRNAs and 122 mRNAs. The Lasso-Cox model fitted OS/PFS to novel prediction models, which integrated clinical factors, ELN risk stratification, mRNA/miRNA expression and methylation profiles. The analysis of time-dependent ROC for our model showed a superior AUC (AUC = 0.916 at 1 year, AUC = 0.916 at 3 years, and AUC = 0.891 at 5 years).

CONCLUSIONS: Low expression of LINC00649 is a potential unfavorable prognostic marker for AML patients, which requires the further validation. The analysis by LASSO-COX regression identified a novel comprehensive model with a superior diagnostic utility, which integrated clinical and genetic variables.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:20

Enthalten in:

BMC cancer - 20(2020), 1 vom: 03. Sept., Seite 841

Sprache:

Englisch

Beteiligte Personen:

Guo, Chao [VerfasserIn]
Gao, Ya-Yue [VerfasserIn]
Ju, Qian-Qian [VerfasserIn]
Zhang, Chun-Xia [VerfasserIn]
Gong, Ming [VerfasserIn]
Li, Zhen-Ling [VerfasserIn]

Links:

Volltext

Themen:

Acute myeloid leukemia
Biomarkers, Tumor
Gene expression profile
Journal Article
Long non-coding RNA
MicroRNAs
RNA, Long Noncoding
RNA, Messenger
Survival analysis

Anmerkungen:

Date Completed 16.04.2021

Date Revised 16.04.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1186/s12885-020-07331-0

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM314560912