Abstract
Recent studies have shown that NOP2, a nucleolar protein, is up-regulated in various cancers, suggesting a potential link to tumor aggressiveness and unfavorable outcomes. This study examines NOP2's role in lung adenocarcinoma (LUAD), a context where its implications remain unclear. Utilizing bioinformatics, we assessed 513 LUAD and 59 normal tissue samples from The Cancer Genome Atlas (TCGA) to explore NOP2's diagnostic and prognostic significance in LUAD. Additionally, in vitro experiments compared NOP2 expression between Beas-2b and A549 cells. Advanced databases and analytical tools, including LINKEDOMICS, STRING, and TISIDB, were employed to further elucidate NOP2's association with LUAD. Our findings indicate a significantly higher expression of NOP2 mRNA and protein in A549 cells compared to Beas-2b cells (P < 0.001). In LUAD, elevated NOP2 levels were linked to decreased Overall Survival (OS) and advanced clinical stages. Univariate Cox analysis revealed that high NOP2 expression correlated with poorer OS in LUAD (P < 0.01), a finding independently supported by multivariate Cox analysis (P < 0.05). The relationship between NOP2 expression and LUAD risk was presented via a Nomogram. Additionally, Gene Set Enrichment Analysis (GSEA) identified seven NOP2-related signaling pathways. A focal point of our research was the interplay between NOP2 and tumor-immune interactions. Notably, a negative correlation was observed between NOP2 expression and the immune infiltration levels of macrophages, neutrophils, mast cells, Natural Killer (NK) cells, and CD8 + T cells in LUAD. Moreover, the expression of NOP2 was related to the sensitivity of various chemotherapeutic drugs. In vitro, we found that downregulating NOP2 can decrease the proliferation, migration and invasion of A549 cells. Furthermore, NOP2 can regulate Caspase3-mediated apoptosis. Collectively, particularly regarding prognosis, immune infiltration and vitro experiments, these findings suggest NOP2's potential of serving as a poor-prognostic biomarker for LUAD and aggravating the malignancy of lung adenocarcinoma cells.
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Data Availability
The RNA-sequencing data and corresponding clinical information were downloaded from the Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/).
NOP2 expression data in various cancers come from TIMER database (http://timer.comp-genomics.org/).
Immunohistochemical picture of lung adenocarcinoma from HPA database (https://www.proteinatlas.org/ENSG00000111641-NOP2/tissue/lung).
The difference data of phosphorylation sites in normal tissues and primary cancer tissues comes from the UALCAN database (http://ualcan.path.uab.edu/cgi-bin/CPTAC-Result.pl?genenam=nop2&ctype=LUAD).
Data related to gene mutation is from cBioPortal database (https://www.cbioportal.org/results/cancerTypesSummary?cancer_study_list=pancan_pcawg_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Ccna&case_set_id=pancan_pcawg_2020_cnaseq&gene_list=NOP2&geneset_list=%20&tab_index=tab_visualize&Action=Submit).
Protein interaction network diagram is from STRING (https://cn.string-db.org/cgi/network?taskId=bQXGyAOwacAE&sessionId=bfFT6WBHvU0K) and GeneMANIA database (http://genemania.org/search/homo-sapiens/nop2).
Tumor immune correlation analysis data is from TISDIB database (http://cis.hku.hk/TISIDB/browse.php?gene=NOP2).
Download cancer and normal cell line data from the bioGPS database (http://biogps.org/#goto=welcome).
NOP2 related genes were downloaded from LinkedOmics database (http://www.linkedomics.org/admin.php).
GO and KEGG enrichment analysis data were from the metascape database (https://metascape.org/gp/index.html#/main/step1).
Drug sensitivity analysis data were from CellMiner database (https://discover.nci.nih.gov/cellminer/home.do) and GSCA online analysis platform (http://bioinfo.life.hust.edu.cn/GSCA/#/).
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Acknowledgements
Our gratitude is extended to the TCGA, bioGPS, HPA, UALCAN, LINKEDOMICS, Metascape, TIMER, STRING, GeneMANIA, cBioPortal, and TISIDB databases for their availability.
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This study was financially supported by China Postdoctoral Science Foundation (2022M721682).
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WZQ, QZ, and GQF contributed to data curation, analysis, investigation, methodology, and manuscript writing; PMW, ZJL, and WL provided guidance and reviewed the thesis. All authors have read and approved the final manuscript.
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Qin, W., Fei, G., Zhou, Q. et al. Nuclear protein NOP2 serves as a poor-prognosis predictor of LUAD and aggravates the malignancy of lung adenocarcinoma cells. Funct Integr Genomics 24, 58 (2024). https://doi.org/10.1007/s10142-024-01337-8
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DOI: https://doi.org/10.1007/s10142-024-01337-8