Multiomics integration reveals the effect of Orexin A on glioblastoma

Abstract

Objectives: This study involved a multi-omics analysis of glioblastoma (GBM) samples to elaborate the potential mechanism of drug treatment.Methods: The GBM cells treated with or without orexin A were acquired from sequencing analysis. Differentially expressed genes/proteins/metabolites (DEGs/ DEPs/ DEMs) were screened. Next, combination analyses were conducted to investigate the common pathways and correlations between the two groups. Lastly, transcriptome-proteome-metabolome association analysis was carried out to determine the common pathways, and the genes in these pathways were analyzed through Kaplan-Meier (K-M) survival analysis in public databases. Cell and animal experiments were performed to investigate the anti-glioma activity of orexin A.Results: A total of 1,527 DEGs, 52 DEPs, and 153 DEMs were found. Moreover, the combination analyses revealed that 6, 4, and 1 common pathways were present in the transcriptome-proteome, proteome-metabolome, and transcriptome-metabolome, respectively. Certain correlations were observed between the two data sets. Finally, 11 common pathways were discovered in association analysis, and 138 common genes were screened out in these common pathways. Six genes showed significant differences in terms of survival in both TCGA and CGGA. In addition, orexin A inhibited the proliferation, migration, and invasion of glioma in vitro and in vivo.Conclusion: Eleven common KEGG pathways with six common genes were found among different omics participations, revealing the underlying mechanisms in different omics and providing theoretical basis and reference for multi-omics research on drug treatment.

Orexin‐A mediates glioblastoma proliferation inhibition by increasing ferroptosis triggered by unstable iron pools and GPX4 depletion

“…A total of 1572 DEGs, 52 DEPs and 116 DEMs were identified in our previous studies (Figure 2A–D ). 22 The result of KEGG enrichment analysis for transcriptome‐proteome‐metabolome combination showed that 11 common pathways were significantly enriched by DEGs, DEPs and DEMs, and ferroptosis is one of them. (Figure 2E ).…”

“…Furthermore, our previous investigations have revealed the antitumor role of orexin‐A in GBM. Through multiple histological analyses of the transcriptome, proteome and metabolome, we have observed that orexin‐A may potentially target ferroptosis, although the specific mechanism remains unclear 22,23 …”

“…Through multiple histological analyses of the transcriptome, proteome and metabolome, we have observed that orexin-A may potentially target ferroptosis, although the specific mechanism remains unclear. 22,23 In this study, we assessed the impact of orexin-A on GBM ferroptosis and delved deeper into the specific mechanism behind orexin-induced GBM ferroptosis. Our findings indicate that orexin-A effectively triggered ferroptosis in GBM while impeding their proliferation.…”

Imaging flow cytometry of tumoroids: A new method for studying GPCR expression

“…Among this large family of GPCRs, the orexins/OX receptor system, which has been extensively studied for its effects on the central nervous system [28], has recently been shown to have anti-inflammatory and anti-tumor properties at the peripheral level [11,14]. In fact, orexins have been demonstrated to induce an antitumor effect against digestive cancers such as colon cancer, pancreatic cancer, and liver cancer as well as nondigestive cancers including prostate cancer [19], and more recently glioblastoma [21]. This breakthrough paradigm revealed that the orexins/OX receptors system could represent a new innovative target in cancer therapy [29].…”

“…In digestive cancer cells, OX1R activation by orexins induced a mitochondrial apoptosis mediated by the recruitment of the tyrosine phosphatase SHP2 [11]. This pro‐apoptotic properties of orexins in cancer cells were induced in a preclinical mouse model where cancer cells from colon or pancreas tumor cells were subcutaneously xenografted in mice, causing strong tumor regression [17, 20, 21]. These observations indicated that the orexins/OX1R system could represent a putative target in the treatment of digestive cancers [11].…”