Serum peptide profiles in patients with carcinoid tumors

Calhoun, Kristine E.; Toth-Fejel, Su Ellen; Cheek, J. Harold; Pommier, Rodney F.

doi:10.1016/s0002-9610(03)00115-6

Cited by 38 publications

(28 citation statements)

References 15 publications

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“…This split product of chromogranin A has been shown to be a sensitive marker in carcinoid and other neuroendocrine tumors. [22][23][24][25] Previously, we showed that a 20% reduction in serum pancreastatin correlated with improved outcome after HACE for carcinoid. 9 Using this same cutoff, responses were seen in 80% of patients including complete response in 14%.…”

Section: Discussionmentioning

confidence: 94%

Hepatic Artery Chemoembolization in 122 Patients with Metastatic Carcinoid Tumor: Lessons Learned

Bloomston

Al-Saif

Klemanski

et al. 2007

Journal of Gastrointestinal Surgery

106

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Section: Discussionmentioning

confidence: 94%

Hepatic Artery Chemoembolization in 122 Patients with Metastatic Carcinoid Tumor: Lessons Learned

Bloomston

Al-Saif

Klemanski

et al. 2007

Journal of Gastrointestinal Surgery

106

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“…Pancreastatin is gaining clinical significance as a smaller, leaner, more specific polypeptide product of CgA. It has been reported to be variously elevated in 58-81% of NETs [53,54]. Despite being a derivative of CgA, pancreastatin levels are not affected by PPI use [55] and, compared with its larger, less predictable parent molecule, has been proposed as a more stable measurement of tumor activity [56].…”

Section: Current Net Biomarkers: Monoanalytesmentioning

confidence: 99%

“…Although pancreastatin showed a greater sensitivity and specificity than CgA in a comparative study [57], this merely offers to improve upon the most troublesome aspects of CgA without solving the underlying difficulties of complex expression in NETs. This is underscored by observations that pancreastatin does not correlate with tumor location, is not associated with tumor functionality and may not correlate with tumor aggressiveness or patient survival [54]. It can be affected by medications or food ingestion e.g.…”

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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“…It is elevated in 58-81% of NETs (Stridsberg et al 1995, Calhoun et al 2003 and does not appear to be elevated by PPI use (Raines et al 2012). Despite recent interest in PST as a biomarker (Ito et al 2012), its utility remains unclear as levels do not correlate with tumor location, are not associated with tumor functionality and may not correlate with tumor aggressiveness or survival (Calhoun et al 2003). It has been proposed that rapid alterations may be prognostic for somatostatin analogbased therapy (Stronge et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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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Serum peptide profiles in patients with carcinoid tumors

Cited by 38 publications

References 15 publications

Hepatic Artery Chemoembolization in 122 Patients with Metastatic Carcinoid Tumor: Lessons Learned

Hepatic Artery Chemoembolization in 122 Patients with Metastatic Carcinoid Tumor: Lessons Learned

Neuroendocrine Tumor Biomarkers: Current Status and Perspectives

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

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