ProApolipoprotein A1: a serum marker of brain metastases in lung cancer patients.
BACKGROUND
Central nervous system (CNS) diagnostics is a promising tool for detection of neurological disorders, including brain metastases. One of the earliest applications of CNS diagnostics was based on serum markers of blood-brain barrier (BBB) dysfunction, which often correlates with acute, chronic, or incipient brain disease. In the case of brain metastases, serum levels of S100beta demonstrated a good negative predictive value comparable to radiologic investigations. However, a confounding factor was the presence of BBB changes due to cerebrovascular disease.


METHODS
Of 103 patients enrolled in a lung cancer study, greater than 50% presented with magnetic resonance imaging (MRI) changes consistent with chronic cerebrovascular disease and reflected by elevated serum S100beta. To unveil serum protein, the authors used proteomic techniques that allow discrimination between patients with brain metastases and lung cancer patients affected by cerebrovascular ischemic changes without infiltrating tumor.


RESULTS
ProApolipoprotein A1, transferrin, haptoglobin, and transthyretin were upregulated in patients affected by chronic cerebrovascular disease and brain metastases compared with those affected only by vascular diseases. ProApolipoprotein A1 was significantly increased (p<.05) in patients with CNS disease.


CONCLUSIONS
In conclusion, these data support the use of serum markers for the early detection of brain metastases. ProApolipoprotein A1 may be used in conjunction with S100beta for serum-based, MRI-independent diagnosis of metastatic brain tumors.
Marchi
Nicola
N
Cerebrovascular Research, Department of Neurosurgery, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio 44195, USA.
Mazzone
Peter
P
Fazio
Vincent
V
Mekhail
Tarek
T
Masaryk
Thomas
T
Janigro
Damir
D
D000230:Adenocarcinoma / Q000097:blood / Q000556:secondary; D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D001812:Blood-Brain Barrier; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000097:blood* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000556:secondary; D002561:Cerebrovascular Disorders / Q000097:blood*; D002908:Chronic Disease; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D006242:Haptoglobins / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000097:blood; D011228:Prealbumin / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D014168:Transferrin / Q000378:metabolism
D016632:Apolipoprotein A-I; D014408:Biomarkers, Tumor; D006242:Haptoglobins; D009414:Nerve Growth Factors; D011228:Prealbumin; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D014168:Transferrin