Research Paper Volume 13, Issue 11 pp 15548—15568

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

Zhang Chen1, , Fan Yang2, , Hui Liu3, , Fan Fan3, , Yanggang Lin1, , Jinhua Zhou1, , Yun Cai4, , Xiaoxiao Zhang5, , Yingxin Wu6, , Rui Mao1,6, , Tongtong Zhang1,6, ,

  • 1 Affiliated Hospital of Southwest Jiaotong University, Chengdu 610036, China
  • 2 Emergency Department, Peking University Third Hospital, Peking University School of Medicine, Beijing 100083, China
  • 3 Department of Neurology, General Hospital of Western Theater Command, Chengdu 610500, China
  • 4 Department of Orthopedics, General Hospital of Western Theater Command, Chengdu 610083, China
  • 5 West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
  • 6 Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University and The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu 610031, China

Received: January 16, 2021       Accepted: May 21, 2021       Published: June 9, 2021      

https://doi.org/10.18632/aging.203116
How to Cite

Copyright: © 2021 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

cALL: Childhood acute lymphoblastic leukemia; LASSO: Least absolute shrinkage and selection operator; lncRNA: Long non-coding RNA; C-index: Concordance index; TARGET: Therapeutically Applicable Research to Generate Effective Treatment; MRD: Minimum residual disease; AUC: ROC curve and the area under the curve.