iTRAQ and two‐dimensional‐LC‐MS/MS reveal NAA10 is a potential biomarker in esophageal squamous cell carcinoma

Wang, Dong; Chen, Jinyan; Han, Junyong; Wang, Kun; Fang, Weimin; Jin, Jingjun; Xue, Shijie

doi:10.1002/prca.202100081

Cited by 5 publications

(3 citation statements)

References 32 publications

(46 reference statements)

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“…Numerous studies have been conducted in recent years to explore the proteomic changes of patients with oesophageal cancer (41)(42)(43)(44). By using Isobaric Tags for Relative and Absolute Quantification (iTRAQ), one study identified 516 differentially expressed proteins in oesophageal cancer tissues and normal tissues adjacent to the cancer, in which N-alpha-acetyltransferase 10 (NAA10) was expressed at reduced levels in oesophageal cancer tissues and NAA10 inhibited the proliferation of OSCC cells; this suggests that NAA10 may serve as a suppressor of OSCC and a new potential diagnostic biomarker for OSCC (45). In addition, the regulatory mechanism of MARCH8 has been elucidated using the iTRAQ technique (46).…”

Section: Discussionmentioning

confidence: 99%

A metabolomic and proteomic study to elucidate the molecular mechanisms of immunotherapy resistance in patients with oesophageal squamous cell carcinoma

Gao

Chen

2023

Biomed Rep

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Systemic chemotherapy, the standard first-line treatment option for patients with advanced oesophageal squamous cell carcinoma (OSCC), results in a median survival of ~1 year. Immune checkpoint inhibitors are a breakthrough oncology treatment option; however, most patients with advanced OSCC develop primary and acquired resistance to programmed death receptor-1 (PD-1) monoclonal antibody, severely affecting their prognosis. Therefore, there is an urgent need to investigate the molecular mechanism underlying resistance to treatment. The present study aimed to explore the mechanism of resistance to PD-1 monoclonal antibody. Plasma samples were collected from patients with OSCC treated with immunotherapy, who achieved pathological response/partial response (CR/PR) or stable disease/progressive disease (SD/PD) after the fourth treatment cycle. TM-widely targeted metabolomics, widely targeted lipidomics, and DIA proteomics assays were performed. Differential metabolites were screened based on fold change (FC) ≥1.5 or ≤0.67 and a VIP ≥1; differential proteins were screened based on FC >1.5 or <0.67 and P<0.05. The identified metabolites were annotated and mapped using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases. The differential proteins were annotated to the Gene Ontology and KEGG pathway databases. A correlation network diagram was drawn using differential expressed proteins and metabolites with (Pearson correlation coefficient) r>0.80 and P<0.05. Finally, 197 and 113 differential metabolites and proteins were screened, respectively, in patients with CR/PR and SD/PD groups. The KEGG enrichment analysis revealed that all of these metabolites and proteins were enriched in cholesterol metabolism and in the NF-κB and phospholipase D signalling pathways. The present study is the first to demonstrate that PD-1 inhibitor resistance may be attributed to cholesterol metabolism or NF-κB and phospholipase D signalling pathway activation. This finding suggests that targeting these signalling pathways may be a promising novel therapeutic approach in OSCC which may improve prognosis in patients undergoing immunotherapy.

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Section: Discussionmentioning

confidence: 99%

A metabolomic and proteomic study to elucidate the molecular mechanisms of immunotherapy resistance in patients with oesophageal squamous cell carcinoma

Gao

Chen

2023

Biomed Rep

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“…Recently, Wang et al reported an opposite effect of Naa10p in regulating tumorigenicity and cell invasion of ESCC [ 31 ]. Their findings demonstrated that Naa10p inhibited proliferation and suppressed migration and invasion of TE-1 cells, supporting Naa10p as a tumor suppressor and potential biomarker for ESCC.…”

Section: Discussionmentioning

confidence: 99%

Naa10p promotes cell invasiveness of esophageal cancer by coordinating the c-Myc and PAI1 regulatory axis

et al. 2022

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N-α-acetyltransferase 10 protein, Naa10p, is involved in various cellular functions impacting tumor progression. Due to its capacity to acetylate a large spectrum of proteins, both oncogenic and tumor-suppressive roles of Naa10p have been documented. Here, we report an oncogenic role of Naa10p in promoting metastasis of esophageal cancer. NAA10 is more highly expressed in esophageal cancer tissues compared to normal tissues. Higher NAA10 expression also correlates with poorer survival of esophageal cancer patients. We found that NAA10 expression was transcriptionally regulated by the critical oncogene c-Myc in esophageal cancer. Furthermore, activation of the c-Myc-Naa10p axis resulted in upregulated cell invasiveness of esophageal cancer. This increased cell invasiveness was also elucidated to depend on the enzymatic activity of Naa10p. Moreover, Naa10p cooperated with Naa15p to interact with the protease inhibitor, PAI1, and prevent its secretion. This inhibition of PAI1 secretion may derive from the N-terminal acetylation effect of the Naa10p/Naa15p complex. Our results establish the significance of Naa10p in driving metastasis in esophageal cancer by coordinating the c-Myc-PAI1 axis, with implications for its potential use as a prognostic biomarker and therapeutic target for esophageal cancer.

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“…Proteomics is a field of large-scale characterization of proteins that provides an effective technique for detection of biomarkers. Isobaric tag for relative and abso-lute quantification (iTRAQ) is an advanced quantitative proteomic approach that has been widely used in multiple fields for the diagnosis and treatment of numerous diseases since its conception in 2004 [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Differential Plasma Proteins Identified via iTRAQ-Based Analysis Serve as Diagnostic Markers of Pancreatic Ductal Adenocarcinoma

et al. 2023

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Objective. We aimed to identify differentially expressed proteins in the plasma of patients with pancreatic cancer and control subjects, which could serve as potential tumor biomarkers. Methods. Differentially expressed proteins were determined via isostatic labeling and absolute quantification (iTRAQ). Potential protein biomarkers were identified via enzyme-linked immunosorbent assay (ELISA) in 40 patients and 40 control subjects, and those eventually selected were further validated in 40 pancreatic cancer and normal pancreatic tissues. Results. In total, 30 proteins displayed significant differences in expression among which 21 were downregulated and 9 were upregulated compared with the control group. ELISA revealed downregulation of peroxiredoxin-2 (PRDX2) and upregulation of alpha-1-antitrypsin (AAT), Ras-related protein Rab-2B (RAB2B), insulin-like growth factor-binding protein 2 (IGFBP2), Rho-related GTP-binding protein RhoC (RHOC), and prelamin-A/C (LMNA) proteins in 40 other samples of pancreatic cancer. Notably, only AAT, RAB2B, and IGFBP2 levels were consistent with expression patterns obtained with iTRAQ. Moreover, all three proteins displayed a marked increase in pancreatic cancer tissues. Data from ROC curve analysis indicated that the diagnostic ability of AAT, RAB2B, and IGFBP2 combined with carbohydrate antigen 19-9 (CA19-9) for pancreatic cancer was significantly greater than that of the single indexes (area under the curve (AUC): 90% vs. 75% (CA19-9), 76% (AAT), 71% (RAB2B), and 71% (IGFBP2), all P < 0.01 ). Conclusion. AAT, RAB2B, and IGFBP2 could serve as effective biomarkers to facilitate the early diagnosis of pancreatic cancer.

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iTRAQ and two‐dimensional‐LC‐MS/MS reveal NAA10 is a potential biomarker in esophageal squamous cell carcinoma

Cited by 5 publications

References 32 publications

A metabolomic and proteomic study to elucidate the molecular mechanisms of immunotherapy resistance in patients with oesophageal squamous cell carcinoma

A metabolomic and proteomic study to elucidate the molecular mechanisms of immunotherapy resistance in patients with oesophageal squamous cell carcinoma

Naa10p promotes cell invasiveness of esophageal cancer by coordinating the c-Myc and PAI1 regulatory axis

Differential Plasma Proteins Identified via iTRAQ-Based Analysis Serve as Diagnostic Markers of Pancreatic Ductal Adenocarcinoma

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