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Comprehensive transcriptomics and proteome analysis to identify prognostic risk factors for MYCN non-amplified
Shan Liu1, Zhihong Wang2, Jianzhen Shen3
1Department of Hematology-Oncology, Fujian Children's Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China.
Background:
MYCN non-amplified (MYCN-NA) neuroblastoma (NB) demonstrates considerable heterogeneity in both biological and clinical aspects, and its molecular and biological characteristics remain inadequately defined.
Methods:
A comprehensive multi-omics analysis was performed on transcriptome and proteome data from 20 MYCN-NA NB tissues, including 11 low- and intermediate-risk neuroblastoma (LIR-NB) cases and 9 high-risk neuroblastoma (HR-NB) cases. Additionally, the expression levels and survival prognostic significance of key candidate genes were systematically assessed using public datasets (GSE85047 and TARGET-NB).
Results:
Transcriptomic analysis revealed 1,955 differentially expressed genes (DEGs), with 899 upregulated and 1,056 downregulated in HR-NB (P < 0.05, |log2FC| ≥ 1.5). Pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes identified significant associations of these DEGs with glycolipid metabolism, signal transduction, and transcriptional regulation. Proteomic profiling identified 609 differentially expressed proteins (DEPs), with 24 upregulated and 585 downregulated in HR-NB. These DEPs were predominantly enriched in metabolic pathways, axon guidance, and Rho GTPase signaling. Integrated omics analysis revealed that both mRNA and protein expression of DPEP1 and FILIP1 were co-upregulated in HR-NB, while seven genes-ICA1L, KCNH2, LGI3, FAM184A, INPP5F, NELL2, and VKORC1L1-were co-downregulated. Genes exhibiting consistent changes in both protein and mRNA levels were primarily involved in glycerophospholipid metabolism and regulation of transport. Moreover, the top five genes (ICA1L, KCNH2, LGI3, FAM184A, and INPP5F) with the most significant concurrent changes were further validated for their expression levels and association with survival prognosis in GSE85047 and TARGET-NB datasets. Notably, increased expression of INPP5F and LGI3 correlated with an improvement in overall survival rate (P < 0.05).
Conclusion:
MYCN-NA HR-NB demonstrates metabolic reprogramming characterized by disorders in glucose and lipid metabolism. Notably, the elevated expression of INPP5F and LGI3 is linked to improved overall survival and may serve as potential therapeutic targets.
