Identification of diagnostic markers involved in the pathogenesis of gastric cancer through iTRAQ-based quantitative proteomics

Jiang, Zhen; Shen, Hongchun; Tang, Bo; Chen, Hui; Yu, Qin; Ji, Xingli; Wang, Li

doi:10.1016/j.dib.2016.12.023

Cited by 9 publications

(5 citation statements)

References 6 publications

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“…The present study identified 431 proteins that were differentially expressed in early‐ or late‐stage cancers, or both, compared with adjacent normal tissues, including 224 increased and 207 decreased proteins (±>1.2‐fold changes), respectively. The overall differently expressed proteins were in the data reports of our series studies for gastric cancer . Among those proteins, GLS1 was found to be upregulated with a 1.68‐fold change in gastric cancer tissues, and GGCT was found to be upregulated with a 1.21‐fold change in gastric cancer tissues.…”

Section: Resultsmentioning

confidence: 85%

iTRAQ‐Based Quantitative Proteomics Approach Identifies Novel Diagnostic Biomarkers That Were Essential for Glutamine Metabolism and Redox Homeostasis for Gastric Cancer

Jiang

Zhang

Gan

et al. 2019

Proteomics Clinical Apps

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Purpose: To screen the novel biomarkers for gastric cancer and to determine the values of glutaminase 1 (GLS1) and gamma-glutamylcyclotransferase (GGCT) for detecting gastric cancer. Experimental design: A discovery group of four paired gastric cancer tissue samples are labeled with Isobaric tag for relative and absolute quantitation agents and identified with LC-ESI-MS/MS. A validation group of 168 gastric cancer samples and 30 healthy controls are used to validate the expression of GLS1 and GGCT. Results: Four hundred and thirty-one proteins are found differentially expressed in gastric cancer tissues. Of these proteins, GLS1 and GGCT are found overexpressed in gastric cancer patients, with sensitivity of 75.6% (95% CI: 69-82.2%) and specificity of 81% (95% CI: 75-87%) for GLS1, and with sensitivity of 63.1% (95% CI: 55.7-71.5%) and specificity of 60.7% (95% CI: 53.3-68.2%) for GGCT. The co-expression of GLS1 and GGCT in gastric cancer tissues has sensitivity of 78.1% (95% CI: 70.1-86.1%) and specificity of 86.5% (95% CI: 79.5-93.4%). Moreover, both GLS1 and GGCT present higher expression of 82.6% (95% CI: 68.5-99.4%) and 73.9% (95% CI: 54.5-93.3%) in lymph node metastasis specimen than those in non-lymph node metastasis specimen. The areas under ROC curves are up to 0.734 for the co-expression of GLS1 and GGCT in gastric cancer. The co-expression of GLS1 and GGCT is strongly associated with histological grade, lymph node metastasis, and TNM stage Ⅲ/Ⅳ. Conclusions and clinical relevance: The present study provides the quantitative proteomic analysis of gastric cancer tissues to identify prognostic biomarkers of gastric cancer. The co-expression level of GLS1 and GGCT is of great clinical value to serve as diagnostic and therapeutic biomarkers for early gastric cancer.

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Section: Resultsmentioning

confidence: 85%

iTRAQ‐Based Quantitative Proteomics Approach Identifies Novel Diagnostic Biomarkers That Were Essential for Glutamine Metabolism and Redox Homeostasis for Gastric Cancer

Jiang

Zhang

Gan

et al. 2019

Proteomics Clinical Apps

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“…To identify the expression of OAT and CPS1, we used a discovery group of four pairs of technical replicates of gastric cancer tissues and adjacent gastric tissues to perform the iTRAQ quantitative proteomics. Our previous studies had showed that 224 proteins were significantly upregulated and 207 proteins were downregulated in gastric cancer relative to paired adjacent gastric tissues 5 . OAT was found to be upregulated with a 1.294 fold changes in gastric cancer tissues, and CPS1 was found to be upregulated with a 1.333 fold changes in gastric cancer tissues.…”

Section: Resultsmentioning

confidence: 86%

“…Our previous studies had showed that 224 proteins were significantly upregulated and 207 proteins were downregulated in gastric cancer relative to paired adjacent gastric tissues. 5 OAT was found to be upregulated with a 1.294 fold changes in gastric cancer tissues, and CPS1 was found to be upregulated with a 1.333 fold changes in gastric cancer tissues. Figure 1 showed the representative MS/MS peptides spectrum for OAT and CPS1 in gastric cancer, respectively.…”

Section: Identification Of Oat and Cps1 The Potential Biomarkers For ...mentioning

confidence: 92%

Ornithine aminotransferase and carbamoyl phosphate synthetase 1 involved in ammonia metabolism serve as novel targets for early stages of gastric cancer

Jiang

Chen

Luo

et al. 2022

Clinical Laboratory Analysis

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Objective The sensitivity and specificity of current biomarkers for gastric cancer were insufficient. The aim of the present study was to screen novel biomarkers and determine the diagnostic values of ornithine aminotransferase (OAT) and carbamoyl phosphate synthetase 1 (CPS1) for detecting gastric cancer. Methods With stable isotope tags, we labelled an initial discovery group of four paired gastric cancer tissue samples and identified with LC‐ESI‐MS/MS. A validation group of 159 gastric cancer samples and 30 healthy controls were used to validate the candidate targets. GSEA was used to explore the pathways activated in gastric cancer. Results Four hundred and thirty one proteins were found differentially expressed in gastric cancer tissues. Of these proteins, OAT and CPS1 were found over‐expressed in gastric cancer patients, with sensitivity of 70.4% (95% CI: 63.3%–77.6%) and specificity of 80.5% (95% CI: 74.3%–86.7%) for ornithine aminotransferase, and with sensitivity of 68.6% (95% CI: 61.3%–75.8%) and specificity of 73% (95% CI: 66%–79.9%) for carbamoyl phosphate synthetase 1. The co‐expression of OAT and CPS1 in gastric cancer tissues has a sensitivity of 81% (95% CI: 73.2%–88.8%) and specificity of 89% (95% CI: 83%–95%). Furthermore, both OAT and CPS1 were overexpressed in patients with local invasion T3 and T4 stages than those in patients with T1 and T2 stages. The co‐expression of OAT and CPS1 was strongly correlated with histological grade I 68% (95% CI: 58.7%–77.3%) and TNM stage I/II 52% (95% CI: 42%–62%). The areas under ROC curves were up to 0.758 for the co‐expression of OAT and CPS1 in gastric cancer. GSEA results showed that two gene sets and 30 gene sets were activated in OAT high‐ and CPS1 high‐expression patients with gastric cancer, respectively. Conclusions The present findings indicated a tight correlation between the co‐expression of OAT and CPS1 and the histological grade, local invasion, and TNM stages of gastric cancer. Therefore, OAT and CPS1 might be predictors for gastric cancer invasion and potential targets for anticancer drug design for gastric cancer.

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“…There is accumulating evidence indicating that FABP1 is up-regulated in a variety of carcinomas, such as prostate, liver and pancreas cancers, although down-regulated in other cancers 41 , 42 . For example, increased levels of FABP1 were reported in the early stage of gastric cancers, with a specificity of 95%, and in the advanced stage of cancer recurrence with a sensitivity of 67%, demonstrating a potential biomarker for the worse prognosis 43 . Agreed with these studies, our current research showed that FABP1 expression was significantly higher in DI region than in T area.…”

Section: Discussionmentioning

confidence: 99%

Fatty Acid Binding Protein 1 is an Independent Prognostic Biomarker for Gallbladder Cancer with Direct Hepatic Invasion

Qiu,

Liu,

et al. 2024

Int. J. Med. Sci.

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Background: Direct liver invasion (DI) is a predominant pathway of gallbladder cancer (GBC) metastasis, but the molecular alterations associated with DI remain addressed. This study identified specific genes correlated with DI, which may offer a potential biomarker for the diagnosis and prognosis of advanced GBC. Methods: RNA samples from 3 patients with DI of GBC were used for RNA-seq analysis. Differentially expressed genes and metabolic pathways between primary tumor (T) and DI tissue was used to analyze aberrant gene expressions. Immunohistochemistry (IHC) of fatty acid binding protein 1 (FABP1) in 62 patients with DI was engaged to evaluate its association with clinicopathological characteristics and prognosis. IHC of CD3 + and CD8 + T cells was analyzed for their correlation with FABP1 expression, clinicopathological features and prognosis. Univariate and multivariate Cox hazards regression analyses were performed to identify independent prognostic factors for disease-free survival (DFS) and overall survival (OS). Results: FABP1 mRNA levels were significantly upregulated in DI region compared to T tissue. IHC results showed identical results with elevated FABP1 (p < 0.0001). Expression of FABP1 in DI region was significantly associated with lymph node metastasis (P = 0.028), reduced DFS (P = 0.013) and OS (P = 0.022); in contrast, its expression in T region was not associated with clinicopathological characteristics and prognosis (P > 0.05). The density of CD8 + T cells in DI region with higher FABP1 expression was significantly lower than that with lower FABP1 expression (p = 0.0084). Multivariate analysis unveiled those hepatic metastatic nodules (HR = 3.35, 95%CI: 1.37-8.15, P = 0.008) and FABP1 expression in DI region (HR = 2.01, 95%CI: 1.05-3.88, P = 0.036) were high risk factors for OS, and FABP1(HR = 2.05, 95%CI: 1.04-4.06, P = 0.039) was also a high risk factor for DFS. Conclusions: Elevated expression of FABP1 in DI region serves as a potential prognostic biomarker for advanced GBC with DI.

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Identification of diagnostic markers involved in the pathogenesis of gastric cancer through iTRAQ-based quantitative proteomics

Cited by 9 publications

References 6 publications

iTRAQ‐Based Quantitative Proteomics Approach Identifies Novel Diagnostic Biomarkers That Were Essential for Glutamine Metabolism and Redox Homeostasis for Gastric Cancer

iTRAQ‐Based Quantitative Proteomics Approach Identifies Novel Diagnostic Biomarkers That Were Essential for Glutamine Metabolism and Redox Homeostasis for Gastric Cancer

Ornithine aminotransferase and carbamoyl phosphate synthetase 1 involved in ammonia metabolism serve as novel targets for early stages of gastric cancer

Fatty Acid Binding Protein 1 is an Independent Prognostic Biomarker for Gallbladder Cancer with Direct Hepatic Invasion

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