Identification of a Seven-lncRNA-mRNA Signature for Recurrence and Prognostic Prediction in Relapsed Acute Lymphoblastic Leukemia Based on WGCNA and LASSO Analyses.

Haiyan Qi,Xiaogang Wang,Xing Jin,Jianping Lan,Long Chi,Wensong Wang,Ulises Urzua

doi:10.1155/2021/6692022

Abstract

Abnormal expressions of long noncoding RNAs (lncRNAs) and protein-encoding messenger RNAs (mRNAs) are important for the development of childhood acute lymphoblastic leukemia (ALL). This study developed an lncRNA-mRNA integrated classifier for the prediction of recurrence and prognosis in relapsed childhood ALL by using several transcriptome data. Weighted gene coexpression network analysis revealed that green, turquoise, yellow, and brown modules were preserved across the TARGET, GSE60926, GSE28460, and GSE17703 datasets, and they were associated with clinical relapse and death status. A total of 184 genes in these four modules were differentially expressed between recurrence and nonrecurrence samples. Least absolute shrinkage and selection operator analysis showed that seven genes constructed a prognostic signature (including one lncRNA: LINC00652 and six mRNAs: INSL3, NIPAL2, REN, RIMS2, RPRM, and SNAP91). Kaplan-Meier curve analysis observed that patients in the high-risk group had a significantly shorter overall survival than those of the low-risk group. Receiver operating characteristic curve analysis demonstrated that this signature had high accuracy in predicting the 5-year overall survival and recurrence outcomes, respectively. LINC00652 may function by coexpressing with the above prognostic genes (INSL3, SNAP91, and REN) and lipid metabolism-related genes (MIA2, APOA1). Accordingly, this lncRNA-mRNA-based classifier may be clinically useful to predict the recurrence and prognosis for childhood ALL. These genes represent new targets to explain the mechanisms for ALL.

Highlights

Acute lymphoblastic leukemia (ALL) which results from the clonal proliferation of immature T- or B-lymphoid cells in the bone marrow is the most common malignant hematologic disorder in childhood, accounting for approximately 35% of all childhood malignancies [1, 2]
Three microarray datasets were enrolled according to the inclusion criteria of (1)-(3), including GSE60926 (n = 50, including 28 recurrence and 22 nonrecurrence; all were B-cell precursor ALL), GSE28460 (n = 98, including 49 recurrence and 49 nonrecurrence; all were B-cell precursor ALL), and GSE17703 (n = 101, including 11 recurrence and 90 nonrecurrence; including B-ALL and T-ALL) which were used for module validation analysis, while two microarray datasets were enrolled because they satisfied the inclusion criteria of (1), (2), and (4), including E-MTAB-1216 (n = 80, including 23 recurrence and 57 nonrecurrence; including B-ALL and T-ALL) and E-MTAB-1205 (n = 50, including 21 recurrence and 29 nonrecurrence; all were T-ALL) which were used for survival validation analysis
After HUGO Gene Nomenclature Committee (HGNC) annotation and comparison, 97 long noncoding RNAs (lncRNAs) and 11,488 protein-encoding messenger RNAs (mRNAs) were found to be shared in all included datasets which were used for the WGCNA analysis

Summary

Introduction

Acute lymphoblastic leukemia (ALL) which results from the clonal proliferation of immature T- or B-lymphoid cells in the bone marrow is the most common malignant hematologic disorder in childhood, accounting for approximately 35% of all childhood malignancies [1, 2]. 10% of patients still will experience relapse, leading to their eventual death [3, 4]. It is considerably essential to early identify cases at a high risk of relapse and predict their overall survival (OS) to schedule more individualized treatments. The rapidly developed molecular technique has led to an expansion of knowledge regarding the pathogenesis of diseases, and several molecular biomarkers have been suggested to predict the relapse and the prognostic outcomes for cancers [5,6,7,8], including ALL. The expression of MK was significantly higher in patients with relapsed ALL than those with CR or at diagnosis. Patients with highly expressed MK harbored poor OS (p = 0:022) and relapse-free survival (RFS, p = 0:047) compared

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