Glycoproteomic Analysis of Bronchoalveolar Lavage (BAL) Fluid Identifies Tumor-Associated Glycoproteins from Lung Adenocarcinoma

Li, Qing Kay; Shah, Punit; Li, Yan; Aiyetan, Paul; Chen, Jing; Yung, Rex; Molena, Daniela; Gabrielson, Edward; Askin, Frederic B.; Chan, Daniel W.; Zhang, Hui

doi:10.1021/pr400274w

Cited by 29 publications

(30 citation statements)

References 42 publications

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“…All these proteins have been reported to show potential anticancer effects. Whereas, other proteins, such as LPCAT2 that is highly expressed in inflammatory cells [ 22 ], BPIFA3 that is highly expressed in lung cancer [ 23 ], PPIA that activates NFkB pathway [ 24 ], and FABP4 that has pro-angiogenic role [ 25 ], were downregulated in SBP1 overexpression xenograft tumors. In contrast, seven glucose metabolism-related proteins were significantly downregulated in SBP1 overexpression xenograft tumors, including GAA, GAPDH, ALDH2, Thioredoxin, ENO3, UGDH and Lumican ( Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

Quantitative Proteomic Analysis Reveals That Anti-Cancer Effects of Selenium-Binding Protein 1 In Vivo Are Associated with Metabolic Pathways

et al. 2015

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Previous studies have shown the tumor-suppressive role of selenium-binding protein 1 (SBP1), but the underlying mechanisms are unclear. In this study, we found that induction of SBP1 showed significant inhibition of colorectal cancer cell growth and metastasis in mice. We further employed isobaric tags for relative and absolute quantitation (iTRAQ) to identify proteins that were involved in SBP1-mediated anti-cancer effects in tumor tissues. We identified 132 differentially expressed proteins, among them, 53 proteins were upregulated and 79 proteins were downregulated. Importantly, many of the differentially altered proteins were associated with lipid/glucose metabolism, which were also linked to Glycolysis, MAPK, Wnt, NF-kB, NOTCH and epithelial-mesenchymal transition (EMT) signaling pathways. These results have revealed a novel mechanism that SBP1-mediated cancer inhibition is through altering lipid/glucose metabolic signaling pathways.

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Section: Resultsmentioning

confidence: 99%

Quantitative Proteomic Analysis Reveals That Anti-Cancer Effects of Selenium-Binding Protein 1 In Vivo Are Associated with Metabolic Pathways

et al. 2015

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“…Multiple biomarkers detectable in bronchial fluids from lung cancer patients have been proposed [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Recently, we have shown that lung cancer cells efficiently activate the classical pathway of complement.…”

Section: Introductionmentioning

confidence: 99%

Elevated Levels of the Complement Activation Product C4d in Bronchial Fluids for the Diagnosis of Lung Cancer

Ajona¹,

Razquín²,

Pastor

et al. 2015

PLoS ONE

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Molecular markers in bronchial fluids may contribute to the diagnosis of lung cancer. We previously observed a significant increase of C4d-containing complement degradation fragments in bronchoalveolar lavage (BAL) supernatants from lung cancer patients in a cohort of 50 cases and 22 controls (CUN cohort). The present study was designed to determine the diagnostic performance of these complement fragments (hereinafter jointly referred as C4d) in bronchial fluids. C4d levels were determined in BAL supernatants from two independent cohorts: the CU cohort (25 cases and 26 controls) and the HUVR cohort (60 cases and 98 controls). A series of spontaneous sputum samples from 68 patients with lung cancer and 10 controls was also used (LCCCIO cohort). Total protein content, complement C4, complement C5a, and CYFRA 21-1 were also measured in all cohorts. C4d levels were significantly increased in BAL samples from lung cancer patients. The area under the ROC curve was 0.82 (95%CI = 0.71–0.94) and 0.67 (95%CI = 0.58–0.76) for the CU and HUVR cohorts, respectively. In addition, unlike the other markers, C4d levels in BAL samples were highly consistent across the CUN, CU and HUVR cohorts. Interestingly, C4d test markedly increased the sensitivity of bronchoscopy in the two cohorts in which cytological data were available (CUN and HUVR cohorts). Finally, in the LCCCIO cohort, C4d levels were higher in sputum supernatants from patients with lung cancer (area under the ROC curve: 0.7; 95%CI = 0.56–0.83). In conclusion, C4d is consistently elevated in bronchial fluids from lung cancer patients and may be used to improve the diagnosis of the disease.

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“…To study glycoprotein expression, researchers have developed a strategy called solid-phase extraction of N-linked glycopeptides (SPEG) to isolate N-linked glycopeptides from biological samples, wherein digested peptides are conjugated to a hydrazide resin and specifically released using peptide-N-glycosidase F 33 . This strategy has been used to identify glycoprotein expression patterns and alterations in a variety of cancer types including ovarian 34 , prostate cancer 35 , breast cancer 36 , and lung cancer 12 , 37 . A limitation of the SPEG technique we used in this study is that it is protein-centric, and information regarding the structure and composition of attached glycan is lost.…”

Section: Discussionmentioning

confidence: 99%

Glycoproteomic Approach Identifies KRAS as a Positive Regulator of CREG1 in Non-small Cell Lung Cancer Cells

Clark¹,

Mei²,

Sun³

et al. 2016

Theranostics

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Protein glycosylation plays a fundamental role in a multitude of biological processes, and the associated aberrant expression of glycoproteins in cancer has made them attractive biomarkers and therapeutic targets. In this study, we examined differentially expressed glycoproteins in cell lines derived from three different states of lung tumorigenesis: an immortalized bronchial epithelial cell (HBE) line, a non-small cell lung cancer (NSCLC) cell line harboring a Kirsten rat sarcoma viral oncogene homolog (KRAS) activation mutation and a NSCLC cell line harboring an epidermal growth factor receptor (EGFR) activation deletion. Using a Triple SILAC proteomic quantification strategy paired with hydrazide chemistry N-linked glycopeptide enrichment, we quantified 118 glycopeptides in the three cell lines derived from 82 glycoproteins. Proteomic profiling revealed 27 glycopeptides overexpressed in both NSCLC cell lines, 6 glycopeptides overexpressed only in the EGFR mutant cells and 19 glycopeptides overexpressed only in the KRAS mutant cells. Further investigation of a panel of NSCLC cell lines found that Cellular repressor of E1A-stimulated genes (CREG1) overexpression was closely correlated with KRAS mutation status in NSCLC cells and could be down-regulated by inhibition of KRAS expression. Our results indicate that CREG1 is a down-stream effector of KRAS in a sub-type of NSCLC cells and a novel candidate biomarker or therapeutic target for KRAS mutant NSCLC.

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Glycoproteomic Analysis of Bronchoalveolar Lavage (BAL) Fluid Identifies Tumor-Associated Glycoproteins from Lung Adenocarcinoma

Cited by 29 publications

References 42 publications

Quantitative Proteomic Analysis Reveals That Anti-Cancer Effects of Selenium-Binding Protein 1 In Vivo Are Associated with Metabolic Pathways

Quantitative Proteomic Analysis Reveals That Anti-Cancer Effects of Selenium-Binding Protein 1 In Vivo Are Associated with Metabolic Pathways

Elevated Levels of the Complement Activation Product C4d in Bronchial Fluids for the Diagnosis of Lung Cancer

Glycoproteomic Approach Identifies KRAS as a Positive Regulator of CREG1 in Non-small Cell Lung Cancer Cells

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