Serum biomarkers of cell death for monitoring therapy response of gastrointestinal carcinomas.
OBJECTIVE
Antitumour treatments are thought to exert their therapeutic efficacy mainly by induction of apoptosis in tumour cells. In epithelial cells, caspases, the key enzymes of apoptosis, cleave the intermediate filament protein cytokeratin (CK)-18 into specific fragments that are released into circulating blood and can be detected by a specific ELISA.


METHODS
To investigate the use of CK-18 fragments as a potential biomarker for the treatment response, we examined the association of serum CK-18 levels and clinical response in 35 patients with gastrointestinal cancers.


RESULTS
While both cleaved and total CK-18 levels were intrinsically elevated in tumour patients, they were further increased during 5-fluorouracil (5-FU)-based therapy. Importantly, the increased levels of CK-18 could discriminate between patients with different clinical response. Cancer patients with a partial response or stable disease revealed a significantly higher increase of cleaved CK-18 during chemotherapy as compared to patients with progressive disease.


CONCLUSIONS
Our results suggest that detection of circulating caspase-cleaved CK-18 might be a useful serum biomarker for monitoring treatment response and should merit further evaluation in larger patient groups.
Brandt
Doreen
D
Department of Gastroenterology, Hannover Medical School, Hannover, Germany.
Volkmann
Xandra
X
Anstätt
Matthias
M
Länger
Florian
F
Manns
Michael P
MP
Schulze-Osthoff
Klaus
K
Bantel
Heike
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D016903:Drug Monitoring / Q000379:methods; D004789:Enzyme Activation; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007150:Immunohistochemistry; D053538:Keratin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D053538:Keratin-18; D020169:Caspases