Abstract:Adenoid cystic carcinoma (ACC) is an extremely rare salivary gland tumor with a poor prognosis and needs attention on molecular mechanisms. Protein ubiquitination is an evolutionarily conserved post-translational modification (PTM) for substrates degradation and control diverse cellular functions. The board cellular function of ubiquitination network holds great promise to detect potential targets and identify respective receptors. Novel technologies are discovered for in-depth research and characterization th… Show more
“…After being instantaneously snap-frozen in liquid nitrogen, the tissues were kept at − 80 °C. The analysis of the proteome [ 14 ] and quantitative ubiquitylomics of post-translational modifications of ubiquitination [ 15 ] in OACC were performed by using these same samples.…”
Purpose
Oral adenoid cystic carcinoma (OACC) has high rates of both local–regional recurrence and distant metastasis. The objective of this study is to investigate the impact of Khib on OACC and its potential as a targeted therapeutic intervention.
Experimental design
We investigated the DEPs (differentially expressed proteins) and DHMPs between OACC-T and OACC-N using LC–MS/MS-based quantitative proteomics and using several bioinformatics methods, including GO enrichment analysis, KEGG pathway analysis, subcellular localization prediction, MEA (motif enrichment analysis), and PPI (protein–protein interaction networks) to illustrate how Khib modification interfere with OACC evolution.
Results
Compared OACC-tumor samples (OACC-T) with the adjacent normal samples (OACC-N), there were 3243 of the DEPs and 2011 Khib sites were identified on 764 proteins (DHMPs). DEPs and DHMPs were strongly associated to glycolysis pathway. GAPDH of K254, ENO of K228, and PGK1 of K323 were modified by Khib in OACC-T. Khib may increase the catalytic efficiency to promote glycolysis pathway and favor OACC progression.
Conclusions and clinical relevance
Khib may play a significant role in the mechanism of OACC progression by influencing the enzyme activity of the glycolysis pathway. These findings may provide new therapeutic options of OACC.
“…After being instantaneously snap-frozen in liquid nitrogen, the tissues were kept at − 80 °C. The analysis of the proteome [ 14 ] and quantitative ubiquitylomics of post-translational modifications of ubiquitination [ 15 ] in OACC were performed by using these same samples.…”
Purpose
Oral adenoid cystic carcinoma (OACC) has high rates of both local–regional recurrence and distant metastasis. The objective of this study is to investigate the impact of Khib on OACC and its potential as a targeted therapeutic intervention.
Experimental design
We investigated the DEPs (differentially expressed proteins) and DHMPs between OACC-T and OACC-N using LC–MS/MS-based quantitative proteomics and using several bioinformatics methods, including GO enrichment analysis, KEGG pathway analysis, subcellular localization prediction, MEA (motif enrichment analysis), and PPI (protein–protein interaction networks) to illustrate how Khib modification interfere with OACC evolution.
Results
Compared OACC-tumor samples (OACC-T) with the adjacent normal samples (OACC-N), there were 3243 of the DEPs and 2011 Khib sites were identified on 764 proteins (DHMPs). DEPs and DHMPs were strongly associated to glycolysis pathway. GAPDH of K254, ENO of K228, and PGK1 of K323 were modified by Khib in OACC-T. Khib may increase the catalytic efficiency to promote glycolysis pathway and favor OACC progression.
Conclusions and clinical relevance
Khib may play a significant role in the mechanism of OACC progression by influencing the enzyme activity of the glycolysis pathway. These findings may provide new therapeutic options of OACC.
“…Salivary gland tumor is a common oral and maxillofacial tumor, of which adenoid cystic carcinoma is a rare type with slow growth, high invasiveness, and ease of metastasis. To further study its molecular mechanism, Li, Wang, et al (2021) 3.2 | Malignant tumors of the digestive system…”
Section: Salivary Gland Tumorsmentioning
confidence: 99%
“…Salivary gland tumor is a common oral and maxillofacial tumor, of which adenoid cystic carcinoma is a rare type with slow growth, high invasiveness, and ease of metastasis. To further study its molecular mechanism, Li, Wang, et al (2021) used 4D‐label‐free ubiquitination proteomics quantitative technology to analyze oral adenoid cystic carcinoma tumors and adjacent normal tissues, identified 4152 ubiquitination sites, obtained 8 protein clusters by analyzing the function of these proteins, and found the role of cytoskeletal ubiquitination and extracellular matrix–related proteins in the occurrence and metastasis of oral adenoid cystic carcinoma can work. These findings can be used as a reference in the development of therapeutic targets for salivary gland tumors.…”
Section: Application Of the Lfq Proteomics Technology For Malignant T...mentioning
Proteomics is the scientific discipline that deals with the protein composition of cells, tissues, and organisms and their patterns of change. It is considered an invaluable tool for tackling many challenges faced in medicine and biology. Among the available approaches, label‐free quantitative proteomics techniques are extensively used to study malignant tumors due to their low cost, simple operation, and short cycle time. Therefore, it provides a novel approach to explore the pathogenesis, diagnostic markers, and targeted drugs of malignant tumors. Here, we summarize the research progress and potential of label‐free quantitative proteomics and discuss the application of such techniques in the research on malignancies.
“…The quantitative proteomic analysis is a useful complementary analysis to genomic and transcriptomic analyses for it provides additional biological information that would have been impossible to get merely by genomics approaches ( 18 ). Proteomic analysis has been demonstrated as a useful tool with the potential to identify cancer biomarkers and find new therapeutic targets in salivary gland ACC, whereas the detailed information on breast ACC is unknown ( 19 – 21 ).…”
BackgroundAdenoid cystic carcinoma (ACC) is a rare type of triple-negative breast cancer that has an indolent clinical behavior. Given the substantial overlapping morphological, immunohistochemical, and molecular features with other basal-like triple-negative breast cancer (BL-TNBC), accurate diagnosis of ACC is crucial for effective clinical treatment. The integrative analysis of the proteome and clinicopathological characteristics may help to distinguish these two neoplasms and provide a deep understanding on biological behaviors and potential target therapy of ACC.MethodsWe applied mass spectrometry-based quantitative proteomics to analyze the protein expression in paired tumor and adjacent normal breast tissue of five ACC and five BL-TNBC. Bioinformatic analyses and the clinicopathological characteristics, including histological features, immunohistochemistry, and FISH results, were also collected to get comprehensive information.ResultsA total of 307 differentially expressed proteins (DEPs) were identified between ACC and BL-TNBC. Clustering analysis of DEPs clearly separated ACC from BL-TNBC. GSEA found downregulation of the immune response of ACC compared with BL-TNBC, which is consistent with the negative PD-L1 expression of ACC. Vesicle-mediated transport was also inhibited, while ECM organization was enriched in ACC. The top upregulated proteins in DEPs were ITGB4, VCAN, and DPT. Moreover, in comparison with normal breast tissue, ACC showed elevated ribosome biogenesis and RNA splicing activity.ConclusionThis study provides evidence that ACC presents a substantially different proteomic profile compared with BL-TNBC and promotes our understanding on the molecular mechanisms and biological processes of ACC, which might be useful for differential diagnosis and anticancer strategy.
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