LINC00649 underexpression is an adverse prognostic marker in acute myeloid leukemia

Autor: Ming Gong, Zhen-Ling Li, Chao Guo, Qian-qian Ju, Ya-yue Gao, Chun-xia Zhang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Down-Regulation
Kaplan-Meier Estimate
lcsh:RC254-282
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Bone Marrow
Surgical oncology
Internal medicine
microRNA
Biomarkers
Tumor
Genetics
medicine
Humans
Gene Regulatory Networks
RNA
Messenger
Survival analysis
Proportional Hazards Models
Acute myeloid leukemia
Competing endogenous RNA
business.industry
Gene Expression Profiling
Myeloid leukemia
Methylation
Middle Aged
Gene expression profile
Prognosis
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Long non-coding RNA
Gene Expression Regulation
Neoplastic
Survival Rate
Leukemia
Myeloid
Acute
MicroRNAs
030104 developmental biology
CpG site
030220 oncology & carcinogenesis
Female
RNA
Long Noncoding
Transcriptome
business
Research Article
Zdroj: BMC Cancer, Vol 20, Iss 1, Pp 1-20 (2020)
BMC Cancer
ISSN: 1471-2407
DOI: 10.1186/s12885-020-07331-0
Popis: 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.
Databáze: OpenAIRE
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