Acute-phase response proteins are related to cachexia and accelerated angiogenesis in gastroesophageal cancers.
BACKGROUND
Accurate outcome prediction in gastroesophageal malignancies is challenging. Acute-phase response proteins (APRPs) have been claimed to be independent prognosticators, although the basis for their association with prognosis remains unexplained. We hypothesized that, similarly to pancreatic and lung cancers, changes in APRPs in gastroesophageal malignancies are associated with cachexia and accelerated angiogenesis.


METHODS
C-reactive protein (CRP), albumin and transferrin serum levels were evaluated and the Glasgow Prognostic Score (GPS) calculated. These data were compared with concentrations of circulating interleukin (IL)-1, IL-6 and IL-8, tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF)-A, VEGF-C and midkine in 96 gastroesophageal cancer patients (49 with cachexia) and 42 healthy subjects.


RESULTS
Albumin and CRP levels were altered in the cancer patients, with further CRP elevation in those with cachexia. Transferrin was decreased only in the cachectic patients. The interrelationships between the APRPs were strengthened in cachexia and only then were APRPs correlated with the cytokines elevated in gastroesophageal cancer-related cachexia: IL-6, IL-8, VEGF-A and midkine. GPS corresponded well to transferrin, IL-1, IL-6, IL-8, TNF-alpha, VEGF-A and midkine concentrations.


CONCLUSIONS
Cachexia in gastroesophageal cancers is associated with changes in APRP concentrations. This, together with a direct relationship of APRPs with accelerated angiogenesis, may constitute a foundation for the association of APRPs and GPS with outcome in these malignancies.
Krzystek-Korpacka
Malgorzata
M
Department of Medical Biochemistry, Wroclaw Medical University, Wroclaw, Poland. krzystek@bioch.am.wroc.pl
Matusiewicz
Malgorzata
M
Diakowska
Dorota
D
Grabowski
Krzysztof
K
Blachut
Katarzyna
K
Kustrzeba-Wojcicka
Irena
I
Terlecki
Grzegorz
G
Gamian
Andrzej
A
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000378:metabolism; D002100:Cachexia / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000098:blood supply / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D013274:Stomach Neoplasms / Q000098:blood supply / Q000150:complications*; D014168:Transferrin / Q000378:metabolism; D015431:Weight Loss
D000209:Acute-Phase Proteins; D016207:Cytokines; D014168:Transferrin; D002097:C-Reactive Protein