Identification of prognostic stemness-related genes in kidney renal papillary cell carcinoma.
Kidney renal papillary cell carcinoma (KIRP)
Notch signaling pathway
Prognosis
Stemness-related gene
Target drugs
mRNA expression-based stemness index
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
03 May 2024
03 May 2024
Historique:
received:
15
08
2023
accepted:
09
04
2024
medline:
4
5
2024
pubmed:
4
5
2024
entrez:
3
5
2024
Statut:
epublish
Résumé
Kidney renal papillary cell carcinoma (KIRP) is the second most prevalent malignant cancer originating from the renal epithelium. Nowadays, cancer stem cells and stemness-related genes (SRGs) are revealed to play important roles in the carcinogenesis and metastasis of various tumors. Consequently, we aim to investigate the underlying mechanisms of SRGs in KIRP. RNA-seq profiles of 141 KIRP samples were downloaded from the TCGA database, based on which we calculated the mRNA expression-based stemness index (mRNAsi). Next, we selected the differentially expressed genes (DEGs) between low- and high-mRNAsi groups. Then, we utilized weighted gene correlation network analysis (WGCNA) and univariate Cox analysis to identify prognostic SRGs. Afterwards, SRGs were included in the multivariate Cox regression analysis to establish a prognostic model. In addition, a regulatory network was constructed by Pearson correlation analysis, incorporating key genes, upstream transcription factors (TFs), and downstream signaling pathways. Finally, we used Connectivity map analysis to identify the potential inhibitors. In total, 1124 genes were characterized as DEGs between low- and high-RNAsi groups. Based on six prognostic SRGs (CCKBR, GPR50, GDNF, SPOCK3, KC877982.1, and MYO15A), a prediction model was established with an area under curve of 0.861. Furthermore, among the TFs, genes, and signaling pathways that had significant correlations, the CBX2-ASPH-Notch signaling pathway was the most significantly correlated. Finally, resveratrol might be a potential inhibitor for KIRP. We suggested that CBX2 could regulate ASPH through activation of the Notch signaling pathway, which might be correlated with the carcinogenesis, development, and unfavorable prognosis of KIRP.
Sections du résumé
BACKGROUND
BACKGROUND
Kidney renal papillary cell carcinoma (KIRP) is the second most prevalent malignant cancer originating from the renal epithelium. Nowadays, cancer stem cells and stemness-related genes (SRGs) are revealed to play important roles in the carcinogenesis and metastasis of various tumors. Consequently, we aim to investigate the underlying mechanisms of SRGs in KIRP.
METHODS
METHODS
RNA-seq profiles of 141 KIRP samples were downloaded from the TCGA database, based on which we calculated the mRNA expression-based stemness index (mRNAsi). Next, we selected the differentially expressed genes (DEGs) between low- and high-mRNAsi groups. Then, we utilized weighted gene correlation network analysis (WGCNA) and univariate Cox analysis to identify prognostic SRGs. Afterwards, SRGs were included in the multivariate Cox regression analysis to establish a prognostic model. In addition, a regulatory network was constructed by Pearson correlation analysis, incorporating key genes, upstream transcription factors (TFs), and downstream signaling pathways. Finally, we used Connectivity map analysis to identify the potential inhibitors.
RESULTS
RESULTS
In total, 1124 genes were characterized as DEGs between low- and high-RNAsi groups. Based on six prognostic SRGs (CCKBR, GPR50, GDNF, SPOCK3, KC877982.1, and MYO15A), a prediction model was established with an area under curve of 0.861. Furthermore, among the TFs, genes, and signaling pathways that had significant correlations, the CBX2-ASPH-Notch signaling pathway was the most significantly correlated. Finally, resveratrol might be a potential inhibitor for KIRP.
CONCLUSIONS
CONCLUSIONS
We suggested that CBX2 could regulate ASPH through activation of the Notch signaling pathway, which might be correlated with the carcinogenesis, development, and unfavorable prognosis of KIRP.
Identifiants
pubmed: 38702698
doi: 10.1186/s12920-024-01870-2
pii: 10.1186/s12920-024-01870-2
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
121Subventions
Organisme : National Natural Science Foundation of China
ID : No. 82173265
Organisme : National Natural Science Foundation of China
ID : No. 81974391
Organisme : Shanghai Rising-Star Program
ID : 23QC1401400
Organisme : Shanghai Municipal Health and Family Planning Commission
ID : 20204Y0042
Organisme : Leading health talents of Shanghai Municipal Health Commission
ID : 2022LJ002
Organisme : Natural Science Foundation of Shanghai Municipality
ID : 23ZR1441300
Organisme : Hospital Funded Clinical Research, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
ID : 21XHDB06
Informations de copyright
© 2024. The Author(s).
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