Proteomic Analysis of Pancreatic Ductal Adenocarcinoma Compared with Normal Adjacent Pancreatic Tissue and Pancreatic Benign Cystadenoma

Cui, Yazhou; Tian, Min; Zong, Min‐Hua; Moua, Teng; Chen, Yu; Lü, Jun; Jiang, Jianjun; Liu, Xiaoyong; Han, Jinxiang

doi:10.1159/000178879

Cited by 54 publications

(47 citation statements)

References 22 publications

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“…The second qualifiying protein is muscle fructose 1,6-bisphosphate aldolase, a key protein in glycolysis. Fructose 1,6-bisphosphate aldolase as well as other metabolic proteins have been implicated as potential biomarker's in a number of diseases such as pancreatic ductal adenocarcinoma 46 , melanoma 47 and Schizophrenia 48 . Metabolic upregulation and high glucose consumption is common in cancer cells, known as the Warburg effect, allowing their aggressive growth.…”

Section: Discussionmentioning

confidence: 99%

Mass Spectrometry (LC–MS/MS) Identified Proteomic Biosignatures of Breast Cancer in Proximal Fluid

Whelan

He²,

Lu³

et al. 2012

J. Proteome Res.

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Summary We have begun an early phase of biomarker discovery in three clinically important types of breast cancer using a panel of human cell lines: HER2 positive, HER2 negative and hormone receptor positive and triple negative (HER2−, ER−, PR−). We identified and characterized the most abundant secreted, sloughed, or leaked proteins released into serum free media from these breast cancer cell lines using a combination of protein fractionation methods before LC-MS/MS mass spectrometry analysis. A total of 249 proteins were detected in the proximal fluid of 7 breast cancer cell lines. The expression of a selected group of high abundance and/or breast cancer specific potential biomarkers including thromobospondin 1, galectin-3 binding protein, cathepsin D, vimentin, zinc-α2-glycoprotein, CD44, and EGFR from the breast cancer cell lines and in their culture media were further validated by Western blot analysis. Interestingly, mass spectrometry identified a cathepsin D protein single-nucleotide polymorphism (SNP) by alanine to valine replacement from the MCF-7 breast cancer cell line. Comparison of each cell line media proteome displayed unique and consistent biosignatures regardless of the individual group classifications demonstrating the potential for stratification of breast cancer. Based on the cell line media proteome, predictive Tree software was able to categorize each cell line as HER2 positive, HER2 negative and hormone receptor positive and triple negative based on only two proteins, muscle fructose 1,6-bisphosphate aldolase and keratin 19. In addition, the predictive Tree software clearly identified MCF-7 cell line overexpresing the HER2 receptor with the SNP cathepsin D biomarker.

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Section: Discussionmentioning

confidence: 99%

Mass Spectrometry (LC–MS/MS) Identified Proteomic Biosignatures of Breast Cancer in Proximal Fluid

Whelan

He²,

Lu³

et al. 2012

J. Proteome Res.

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“…In this region, IGSF21 and AKR7A2 are located next to the SNPs that show the strongest signals, respectively. IGSF21 belongs to the immunoglobin superfamily, while AKR7A2 is involved in the detoxification of aldehydes and ketones, and is implicated in various cancers such as pancreatic cancer (Praml et al 2008;Cui et al 2009). Another region with over-represented African ancestry is 2q37, in which PDCD1 is involved in signaling of the immune system and various diseases.…”

Section: à16mentioning

confidence: 99%

Genome-wide detection of natural selection in African Americans pre- and post-admixture

Jin¹,

Xu²,

Wang³

et al. 2011

Genome Res.

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It is particularly meaningful to investigate natural selection in African Americans (AfA) due to the high mortality their African ancestry has experienced in history. In this study, we examined 491,526 autosomal single nucleotide polymorphisms (SNPs) genotyped in 5210 individuals and conducted a genome-wide search for selection signals in 1890 AfA. Several genomic regions showing an excess of African or European ancestry, which were considered the footprints of selection since population admixture, were detected based on a commonly used approach. However, we also developed a new strategy to detect natural selection both pre-and post-admixture by reconstructing an ancestral African population (AAF) from inferred African components of ancestry in AfA and comparing it with indigenous African populations (IAF). Interestingly, many selection-candidate genes identified by the new approach were associated with AfA-specific highrisk diseases such as prostate cancer and hypertension, suggesting an important role these disease-related genes might have played in adapting to a new environment. CD36 and HBB, whose mutations confer a degree of protection against malaria, were also located in the highly differentiated regions between AAF and IAF. Further analysis showed that the frequencies of alleles protecting against malaria in AAF were lower than those in IAF, which is consistent with the relaxed selection pressure of malaria in the New World. There is no overlap between the top candidate genes detected by the two approaches, indicating the different environmental pressures AfA experienced pre-and post-population admixture. We suggest that the new approach is reasonably powerful and can also be applied to other admixed populations such as Latinos and Uyghurs.

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“…Proteins by virtue of being the functional denominators of cellular phenotype have garnered a lot of attention as potential biomarkers in cancer. Most of the proteomics approaches for PDAC have focused on assessment of tissue proteome [25], [26], [27] and to some extent examination of proteins secreted in the pancreatic juice [18], [22], [23], [28]. The latter constitutes a rich source of cancer-specific proteome contributed by cellular turnover and degradation of highly proliferative cancer cells that are shed into the juice.…”

Section: Introductionmentioning

confidence: 99%

Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

et al. 2011

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Pancreatic Adenocarcinoma (PDAC), the fourth highest cause of cancer related deaths in the United States, has the most aggressive presentation resulting in a very short median survival time for the affected patients. Early detection of PDAC is confounded by lack of specific markers that has motivated the use of high throughput molecular approaches to delineate potential biomarkers. To pursue identification of a distinct marker, this study profiled the secretory proteome in 16 PDAC, 2 carcinoma in situ (CIS) and 7 benign patients using label-free mass spectrometry coupled to 1D-SDS-PAGE and Strong Cation-Exchange Chromatography (SCX). A total of 431 proteins were detected of which 56 were found to be significantly elevated in PDAC. Included in this differential set were Parkinson disease autosomal recessive, early onset 7 (PARK 7) and Alpha Synuclein (aSyn), both of which are known to be pathognomonic to Parkinson's disease as well as metabolic enzymes like Purine Nucleoside Phosphorylase (NP) which has been exploited as therapeutic target in cancers. Tissue Microarray analysis confirmed higher expression of aSyn and NP in ductal epithelia of pancreatic tumors compared to benign ducts. Furthermore, extent of both aSyn and NP staining positively correlated with tumor stage and perineural invasion while their intensity of staining correlated with the existence of metastatic lesions in the PDAC tissues. From the biomarker perspective, NP protein levels were higher in PDAC sera and furthermore serum levels of its downstream metabolites guanosine and adenosine were able to distinguish PDAC from benign in an unsupervised hierarchical classification model. Overall, this study for the first time describes elevated levels of aSyn in PDAC as well as highlights the potential of evaluating NP protein expression and levels of its downstream metabolites to develop a multiplex panel for non-invasive detection of PDAC.

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Proteomic Analysis of Pancreatic Ductal Adenocarcinoma Compared with Normal Adjacent Pancreatic Tissue and Pancreatic Benign Cystadenoma

Cited by 54 publications

References 22 publications

Mass Spectrometry (LC–MS/MS) Identified Proteomic Biosignatures of Breast Cancer in Proximal Fluid

Mass Spectrometry (LC–MS/MS) Identified Proteomic Biosignatures of Breast Cancer in Proximal Fluid

Genome-wide detection of natural selection in African Americans pre- and post-admixture

Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

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