Principal Component Analysis, Hierarchical Clustering, and Decision Tree Assessment of Plasma mRNA and Hormone Levels as an Early Detection Strategy for Small Intestinal Neuroendocrine (Carcinoid) Tumors

Incidence of neuroendocrine tumors (NETs) is increasing (approximately 6%/year), but clinical presentation is nonspecific, resulting in delays in diagnosis (5–7 years; approximately 70% have metastases). This reflects absence of a sensitive plasma marker. The aim of this study is to investigate whet...

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Bibliographic Details
Published in:Annals of surgical oncology 2009-02, Vol.16 (2), p.487-498
Main Authors: Modlin, Irvin M., Gustafsson, Björn I., Drozdov, Ignat, Nadler, Boaz, Pfragner, Roswitha, Kidd, Mark
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor - blood
Biomarkers, Tumor - genetics
Carcinoid Tumor - blood
Case-Control Studies
Chromogranin A - blood
Cluster Analysis
Connective Tissue Growth Factor - blood
Decision Trees
Early Diagnosis
Endocrine Tumors
Enzyme-Linked Immunosorbent Assay
Female
Humans
Intestinal Neoplasms - blood
Intestine, Small
Male
Medicine
Medicine & Public Health
Middle Aged
Neoplasm Staging
Oncology
Principal Component Analysis
Prognosis
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - blood
RNA, Messenger - genetics
RNA, Neoplasm - blood
RNA, Neoplasm - genetics
Sensitivity and Specificity
Surgery
Surgical Oncology
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Summary:Incidence of neuroendocrine tumors (NETs) is increasing (approximately 6%/year), but clinical presentation is nonspecific, resulting in delays in diagnosis (5–7 years; approximately 70% have metastases). This reflects absence of a sensitive plasma marker. The aim of this study is to investigate whether detection of circulating messenger RNA (mRNA) alone or in combination with circulating NET-related hormones and growth factors can detect gastrointestinal NET disease. The small intestinal (SI) NET cell line KRJ-I was used to define the sensitivity of real-time polymerase chain reaction (PCR) for mRNA detection in blood. NSE , Tph-1 , and VMAT 2 transcripts were identified from one KRJ-I cell/ml blood. mRNA from the tissue and plasma of SI-NETs ( n  = 12) and gastric NETs ( n  = 7), and plasma from healthy controls ( n  = 9) was isolated and real-time PCR performed. Tph-1 was a specific marker of SI-NETs (58%, p  
ISSN:1068-9265
1534-4681
DOI:10.1245/s10434-008-0251-1