Development of a Highly Sensitive and Specific Carboxy-Terminal Human Pancreastatin Assay to Monitor Neuroendocrine Tumor Behavior

O’Dorisio, Thomas M.; Krutzik, Siegfried; Woltering, Eugene A.; Lindholm, Erika; Joseph, Saju; Gandolfi, Abby E.; Wang, Yi Zarn; Boudreaux, J Philip; Vinik, Aaron I.; Go, Vay Liang W.; Howe, James R.; Halfdanarson, Thor; O’Dorisio, M. Sue; Mamikunian, Gregg

doi:10.1097/mpa.0b013e3181c68d7a

Cited by 41 publications

(26 citation statements)

References 19 publications

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“…We could therefore identify no overall effect of PPIs on PST (no differences in PPI-treated and non-treated controls), which presumably reflects the heterogeneity in secretion of this peptide family following prohormone cleavage (Udupi et al 1999). While others have identified correlations between CgA and PST (Syversen et al 1994), we could identify no statistically significant relationship; this is consistent with previous assays (Stronge et al 2008, O'Dorisio et al 2010. CgA is also elevated in hypertension (Takiyyuddin et al 1995) (particularly when not treated (O'Connor 1985)).…”

Section: Discussionsupporting

confidence: 78%

“…In the current study, for example, PST levels were all !40 pmol/l irrespective of tumor or control in Set 2, while only three of 20 NETs in Set 1 had levels greater than this. Other studies have determined cut-offs of 25-50 pmol/l for 'normal' depending on the test platform (Stronge et al 2008, O'Dorisio et al 2010. We identified the same issue with NKA where cut-offs range from 0.8 pg to 2 ng/ml depending on the kit type used (Turner et al 2006).…”

Section: Discussionmentioning

confidence: 80%

“…In addition, this disglycemic peptide is elevated in diabetics (Valicherla et al 2013) as well as in hyperparathyroidism (Bergenfelz et al 2000). Different conformations of the peptide may also be masked and are unavailable for assessment rendering assay interpretation complex and controversial (O'Dorisio et al 2010).…”

Section: Introductionmentioning

confidence: 99%

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A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

Modlin

Drozdov

Alaimo

et al. 2014

Endocrine-Related Cancer

103

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A critical requirement in neuroendocrine tumor (NET) management is a sensitive, specific and reproducible blood biomarker test. We evaluated a PCR-based 51 transcript signature (NETest) and compared it to chromogranin A (CgA), pancreastatin (PST) and neurokinin A (NKA). The multigene signature was evaluated in two groups: i) a validation set of 40 NETs and controls and ii) a prospectively collected group of NETs (nZ41, 61% small intestinal, 50% metastatic, 44% currently treated and 41 age-sex matched controls). Samples were analyzed by a two-step PCR (51 marker genes) protocol and ELISAs for CgA, PST and NKA. Sensitivity comparisons included c 2 , non-parametric measurements, ROC curves and predictive feature importance (PFAI) analyses. NETest identified 38 of 41 NETs. Performance metrics were: sensitivity 92.8%, specificity 92.8%, positive predictive value 92.8% and negative predictive value 92.8%. Single analyte ELISA metrics were: CgA 76, 59, 65, and 71%; PST 63, 56, 59, and 61% and NKA 39, 93, 84, and 60%. The AUCs (ROC analysis) were: NETest: 0.96G0.025, CgA: 0.67G0.06, PST 0.56G0.06, NKA: 0.66G0.06. NETest significantly outperformed single analyte tests (area differences: 0.284-0.403, Z-statistic 4.85-5.9, P!0.0001). PFAI analysis determined NETest had most value (69%) in diagnosis (CgA (13%), PST (9%), and NKA (9%)). Test data were consistent with the validation set (NETest O95% sensitivity and specificity, AUC Z0.98 vs single analytes: 59-67% sensitivity, AUCs: 0.58-0.63). The NETest is significantly more sensitive and efficient (O93%) than single analyte assays (CgA, PST or NKA) in NET diagnosis. Blood-based multigene analytic measurement will facilitate early detection of disease recurrence and can predict therapeutic efficacy.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 80%

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A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

Modlin

Drozdov

Alaimo

et al. 2014

Endocrine-Related Cancer

103

View full text Add to dashboard Cite

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“…glucose may alter test results [58], and levels have been reported to be elevated in diabetics [59] as well as in hyperparathyroidism [60]. Some investigators consider that different conformations of the peptide occur and ‘masking' may render assay interpretation complex and controversial [61]. …”

Section: Current Net Biomarkers: Monoanalytesmentioning

confidence: 99%

Neuroendocrine Tumor Biomarkers: Current Status and Perspectives

et al. 2014

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The identification of accurate harbingers of disease status and therapeutic efficacy are critical requirements in precise diagnosis and effective management. Initially, tissue analysis was regarded as ideal but invasive strategies represent risk compared with peripheral blood sampling. Thus far, most biomarkers, whether in tissue or blood/urine, have been single analytes with varying degrees of sensitivity and specificity. Some analytes have not exhibited robust metrics or have lacked methodological rigor. Neuroendocrine disease represents an area of dire biomarker paucity since the individual biomarkers (gastrin, insulin, etc.) are not widely applicable to the diverse types of neuroendocrine neoplasia. Broad-spectrum markers such as chromogranin A have limitations in sensitivity, specificity and reproducibility. Monoanalytes cannot define the multiple variables (proliferation, metabolic activity, invasive potential, metastatic propensity) that constitute tumor growth. The restricted status of the neuroendocrine neoplasia field has resulted in a lack of comprehensive knowledge of the molecular and cellular biology of the disease, with tardy application of innovative technology. This overview examines limitations in current practice and describes contemporary viable strategies under evaluation, including the identification of novel analytes (gene transcripts, microRNA), circulating tumor cells and metabolic imaging agents that identify disease. Novel requirements are necessary to develop biomathematical algorithms for synchronous calibration of multiple molecular markers and predictive nomograms that interface biological variables to delineate disease progress or treatment efficacy. Optimally, the application of novel techniques and amalgamations of multianalyte assessment will provide a personalized molecular disease signature extrapolative of neuroendocrine neoplasia status and likelihood of progression and predictive of therapeutic opportunity.

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“…Therefore, the possibility of pancreatic NC should be considered when a tumor is detected in the pancreas in the absence of high CA19-9 levels. Because CgA is a serum marker of neuroendocrine tumors in the pancreas, the raised serum level of CgA suggests the diagnosis of neuroendocrine tumors [5]. However, in general, pathological and immunohistochemical examinations are necessary to make the final diagnosis [6].…”

Section: Discussionmentioning

confidence: 99%

Refractory Gastroesophageal Variceal Bleeding Secondary to Neuroendocrine Carcinoma in the Pancreatic Tail

2011

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Development of a Highly Sensitive and Specific Carboxy-Terminal Human Pancreastatin Assay to Monitor Neuroendocrine Tumor Behavior

Abstract: This highly specific, sensitive pancreastatin assay can detect small changes in liver tumor progression and is up to 100-fold more sensitive and specific than CgA assays in the United States.

Cited by 41 publications

References 19 publications

A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

Neuroendocrine Tumor Biomarkers: Current Status and Perspectives

Refractory Gastroesophageal Variceal Bleeding Secondary to Neuroendocrine Carcinoma in the Pancreatic Tail

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