Joint analysis of the metabolomics and transcriptomics uncovers the dysregulated network and develops the diagnostic model of high-risk neuroblastoma.

Bang Du, Fei Zhang, Qiumei Zhou, Weyland Cheng, Zhidan Yu, Lifeng Li, Jianwei Yang, Xianwei Zhang, Chongchen Zhou, Wancun Zhang

Journal: Scientific reports 2023;13(1):16991

PMID: 37813883

Free Full Text on Nature Publishing Group View on PubMed

Abstract

High-risk neuroblastoma (HR-NB) has a significantly lower survival rate compared to low- and intermediate-risk NB (LIR-NB) due to the lack of risk classification diagnostic models and effective therapeutic targets. The present study aims to characterize the differences between neuroblastomas with different risks through transcriptomic and metabolomic, and establish an early diagnostic model for risk classification of neuroblastoma.Plasma samples from 58 HR-NB and 38 LIR-NB patients were used for metabolomics analysis. Meanwhile, NB tissue samples from 32 HR-NB and 23 LIR-NB patients were used for transcriptomics analysis. In particular, integrative metabolomics and transcriptomic analysis was performed between HR-NB and LIR-NB. A total of 44 metabolites (P < 0.05 and fold change > 1.5) were altered, including 12 that increased and 32 that decreased in HR-NB. A total of 1,408 mRNAs (P < 0.05 and |log(fold change)|> 1) showed significantly altered in HR-NB, of which 1,116 were upregulated and 292 were downregulated. Joint analysis of both omic data identified 4 aberrant pathways (P < 0.05 and impact ≥ 0.5) consisting of glycerolipid metabolism, retinol metabolism, arginine biosynthesis and linoleic acid metabolism. Importantly, a HR-NB risk classification diagnostic model was developed using plasma circulating-free S100A9, CDK2, and UNC5D, with an area under receiver operating characteristic curve of 0.837 where the sensitivity and specificity in the validation set were both 80.0%. This study presents a novel pioneering study demonstrating the metabolomics and transcriptomics profiles of HR-NB. The glycerolipid metabolism, retinol metabolism, arginine biosynthesis and linoleic acid metabolism were altered in HR-NB. The risk classification diagnostic model based on S100A9, CDK2, and UNC5D can be clinically used for HR-NB risk classification.

Address: Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, 450018, China.; Henan International Joint Laboratory for Prevention and Treatment of Pediatric Disease, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, 450018, China.; Health Commission of Henan Province Key Laboratory for Precision Diagnosis and Treatment of Pediatric Tumor, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, 450018, China.; Experimental Center of Clinical Research, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230000, China.; Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, 450018, China. [email protected].; Henan International Joint Laboratory for Prevention and Treatment of Pediatric Disease, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, 450018, China. [email protected].; Health Commission of Henan Province Key Laboratory for Precision Diagnosis and Treatment of Pediatric Tumor, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, 450018, China. [email protected].; Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, 450018, China. [email protected].; Henan International Joint Laboratory for Prevention and Treatment of Pediatric Disease, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, 450018, China. [email protected].; Health Commission of Henan Province Key Laboratory for Precision Diagnosis and Treatment of Pediatric Tumor, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, 450018, China. [email protected].; Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, 450018, China. [email protected].; Henan International Joint Laboratory for Prevention and Treatment of Pediatric Disease, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, 450018, China. [email protected].; Health Commission of Henan Province Key Laboratory for Precision Diagnosis and Treatment of Pediatric Tumor, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, 450018, China. [email protected].

DOI: 10.1038/s41598-023-43988-w

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/neuroblastoma.html

Miscellaneous:

https://assays.cancer.gov/non-CPTAC-1155

MeSH Terms: Humans, Transcriptome, Linoleic Acid, Vitamin A, Neuroblastoma, Metabolomics, Arginine