Diagnosis of Pancreatic Cancer Using Serum Proteomic Profiling

Bhattacharyya, Sudeepa; Siegel, Eric R.; Petersen, Gloria M.; Chari, Suresh T.; Suva, Larry J.; Haun, Randy S.

doi:10.1593/neo.04262

Cited by 84 publications

(59 citation statements)

References 27 publications

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“…All solution additions and washes were done using a Biomek 2 robotic liquid handling system (Beckman Coulter, Fullerton, CA). Each chip was analyzed in a Ciphergen SELDI PBSII reader as described (22).…”

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confidence: 99%

Tumor-Derived Interleukin-8 Stimulates Osteolysis Independent of the Receptor Activator of Nuclear Factor-κB Ligand Pathway

et al. 2005

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Bone is a common site of cancer metastasis. Breast, prostate, and lung cancers show a predilection to metastasize to bone. Recently, we reported that the chemokine interleukin 8 (IL-8) stimulates both human osteoclast formation and bone resorption. IL-8 mRNA expression was surveyed in a panel of human breast cancer lines MDA-MET, MDA-MB-231, MDA-MB-435, MCF-7, T47D, and ZR-75, and the human lung adenocarcinoma cell line A549. IL-8 mRNA expression was higher in cell lines with higher osteolytic potential in vivo. Human osteoclast formation was increased by MDA-MET or A549 cell-conditioned medium, but not by MDA-MB-231. Pharmacologic doses of receptor activator of nuclear factor-KB (RANK)-Fc or osteoprotogerin had no effect on the pro-osteoclastogenic activity of the conditioned medium; however, osteoclast formation stimulated by conditioned medium was inhibited 60% by an IL-8-specific neutralizing antibody. The data support a model in which tumor cells cause osteolytic bone destruction independently of the RANK ligand (RANKL) pathway. Tumorproduced IL-8 is a major contributor to this process. The role of secreted IL-8 isoforms was examined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, which detected distinct IL-8 isoforms secreted by MDA-MET and MDA-231 cells, suggesting different pro-osteoclastogenic activities of the two IL-8-derived peptides. These data indicate that (a) osteoclast formation induced by MDA-MET breast cancer cells and A549 adenocarcinoma cells is primarily mediated by IL-8, (b) cell-specific isoforms of IL-8 with distinct osteoclastogenic activities are produced by tumor cells, and (c) tumor cells that support osteoclast formation independent of RANKL secrete other pro-osteoclastogenic factors in addition to IL-8. (Cancer Res 2005; 65(23): 11001-9)

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Tumor-Derived Interleukin-8 Stimulates Osteolysis Independent of the Receptor Activator of Nuclear Factor-κB Ligand Pathway

et al. 2005

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“…Further characterization and sequencing of these key features should provide new insights into disease etiology, and presumably, intervention (33). Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) has emerged as the primary investigator-based modality for biomarker discovery of early stage cancers (31,34), although the approach does have some limitations that have been identified of late (35,36).…”

Section: Functional Annotation Of Gene Expression Profilingmentioning

confidence: 99%

“…These include reproducibility, contributory effects of nonspecific interference by circulatory molecules unrelated to tumor biology, and the lack of standardization of specimen collection, preparation, and techniques used in detecting differentiating m/z peaks, among others. These valid concerns are continually being addressed (34,41). However, it is critical to note that the pipeline of new biomarkers for cancer diagnosis and/or for tracking cancer progression is drying up (42,43).…”

Section: Functional Annotation Of Gene Expression Profilingmentioning

confidence: 99%

Genomics and Proteomics of Bone Cancer

Marguiles

Klimberg

Bhattacharrya

et al. 2006

Clinical Cancer Research

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Although the control of bone metastasis has been the focus of intensive investigation, relatively little is known about the molecular mechanisms that regulate or predict the process, even though widespread skeletal dissemination is an important step in the progression of many tumors. As a result, understanding the complex interactions contributing to the metastatic behavior of tumor cells is essential for the development of effective therapies. Using a state-of-the-art combination of gene expression profiling and functional annotation of human tumor cells, and surfaceenhanced laser desorption/ionization time-of-flight mass spectrometry of patient serum, we have shown that changes in tumor biochemistry correlate with disease progression and help to define the aggressive tumor phenotype. Based on these approaches, it is apparent that the metastatic phenotype of tumor cells is extremely complex. The identification of the phenotype of tumor cells has benefited greatly from the application of gene expression profiling (microarray analysis). This technology has been used by many investigators to identify changes in gene expression and cytokine and growth factor elaboration (such as interleukin 8). The tumor phenotype(s) presumably also include changes in the cell surface carbohydrate profile (via altered glycosyltransferase expression) and heparan sulfate expression (via increased heparanase activity), to name but a few. These specific alterations in gene expression, identified by functional annotation of accumulated microarray data, have been validated using a variety of approaches. Collectively, the data described here suggest that each of these activities is associated with distinct aspects of the aggressive tumor cell phenotype. Collectively, the data suggest that multiple factors constitute the complex phenotype of metastatic tumor cells. In particular, the differences observed in gene expression profiles and serum protein biomarkers play a critical role in defining the mechanisms responsible for bone-specific colonization and growth of tumors in bone. Future studies will identify the mechanisms that participate in the formation of secondary tumor growths of cancers in bone.

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“…15 (25), CA195 (26), TATI (27), POA (28 -30), YKL-40 (31), TUM2-PK (32). Other markers such as peptides identified by surface-enhanced laser desorption and ionization (33,34), and other markers such as MUC4 (35) and synuclein (36) may prove useful but await confirmatory studies and assays optimized for serum analysis. We recently showed that combined serum MIC-1 and CA19-9 measurements had superior diagnostic utility compared with CA19-9 alone for differentiating patients with pancreatic cancer from those without periampullary neoplasia (15).…”

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confidence: 99%

Serum Markers in Patients with Resectable Pancreatic Adenocarcinoma: Macrophage Inhibitory Cytokine 1 versus CA19-9

Koopmann¹,

Rosenzweig²,

Zhang³

et al. 2006

Clinical Cancer Research

203

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Purpose: More accurate serum markers of pancreatic cancer could improve the early detection and prognosis of this deadly disease. We compared the diagnostic utility of a panel of candidate serum markers of pancreatic cancer. Experimental Design: We collected preoperative serum from 50 patients with resectable pancreatic adenocarcinoma, as well as sera from 50 patients with chronic pancreatitis and 50 age/ sex-matched healthy controls from our institution. Sera were analyzed for the following candidate markers of pancreatic cancer: CA19-9, macrophage inhibitory cytokine 1 (MIC-1), osteopontin, tissue inhibitor of metalloproteinase 1, and hepatocarcinoma-intestine-pancreas protein levels. Results: By logistic regression analysis, MIC-1and CA19-9 were significant independent predictors of diagnosis. Receiver operating characteristic curve analysis showed that MIC-1was significantly better than CA19-9 in differentiating patients with pancreatic cancer from healthy controls (area under the curve is 0.99 and 0.78, respectively; P = 0.003), but not in distinguishing pancreatic cancer from chronic pancreatitis (area under the curve of 0.81 and 0.74, respectively; P = 0.63). Hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein, osteopontin, and tissue inhibitor of metalloproteinase 1serum levels did not provide additional diagnostic power. Conclusion: In the differentiation of patients with resectable pancreatic cancer from controls, serum MIC-1outperforms other markers including CA19-9.

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Diagnosis of Pancreatic Cancer Using Serum Proteomic Profiling

Cited by 84 publications

References 27 publications

Tumor-Derived Interleukin-8 Stimulates Osteolysis Independent of the Receptor Activator of Nuclear Factor-κB Ligand Pathway

Tumor-Derived Interleukin-8 Stimulates Osteolysis Independent of the Receptor Activator of Nuclear Factor-κB Ligand Pathway

Genomics and Proteomics of Bone Cancer

Serum Markers in Patients with Resectable Pancreatic Adenocarcinoma: Macrophage Inhibitory Cytokine 1 versus CA19-9

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