Identification of a nomogram based on an 8-lncRNA signature as a novel diagnostic biomarker for childhood acute lymphoblastic leukemia

Aging (Albany NY). 2021 Jun 9;13(11):15548-15568. doi: 10.18632/aging.203116. Epub 2021 Jun 9.

Abstract

Childhood acute lymphoblastic leukemia (cALL) still represents a major cause of disease-related death in children. This study aimed to explore the prognostic value of long non-coding RNAs (lncRNAs) in cALL. We downloaded lncRNA expression profiles from the TARGET and GEO databases. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were applied to identify lncRNA-based signatures. We identified an eight-lncRNA signature (LINC00630, HDAC2-AS2, LINC01278, AL356599.1, AC114490.1, AL132639.3, FUT8.AS1, and TTC28.AS1), which separated the patients into two groups with significantly different overall survival rates. A nomogram based on the signature, BCR ABL1 status and white blood cell count at diagnosis was developed and showed good accuracy for predicting the 3-, 5- and 7-year survival probability of cALL patients. The C-index values of the nomogram in the training and internal validation set reached 0.8 (95% CI, 0.757 to 0.843) and 0.806 (95% CI, 0.728 to 0.884), respectively. The nomogram proposed in this study objectively and accurately predicted the prognosis of cALL. In vitro experiments suggested that LINC01278 promoted the proliferation of leukemic cells and inhibited leukemic cell apoptosis by targeting the inhibition of miR-500b-3p in cALL, and LINC01278 may be a biological target for the treatment of cALL in the future.

Keywords: LINC01278; childhood acute lymphoblastic leukemia; hsa-miR-500b; nomogram; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Child
  • Databases, Genetic
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Leukemic*
  • Gene Regulatory Networks
  • Humans
  • Male
  • Molecular Sequence Annotation
  • Multivariate Analysis
  • Nomograms*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Prognosis
  • Proportional Hazards Models
  • RNA, Long Noncoding / genetics*
  • Reproducibility of Results
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding