학술논문

Circulating caspase-cleaved cytokeratin 18 correlates with tumour burden and response to therapy in patients with colorectal cancer liver metastasis.
Document Type
Article
Source
Clinica Chimica Acta. Jan2023, Vol. 538, p53-59. 7p.
Subject
*IRINOTECAN
*COLORECTAL liver metastasis
*CIRCULATING tumor DNA
*KERATIN
*CANCER patients
*TREATMENT effectiveness
*CANCER chemotherapy
*TUMOR markers
Language
ISSN
0009-8981
Abstract
[Display omitted] • Liver metastases from colorectal cancer contain areas of apoptotic tumour cells. • Apoptotic cell debris is released into the bloodstream. • Systemic levels of the apoptosis marker M30 correlate with tumour volume and predict the likelihood of tumour shrinkage in response to chemotherapy. Systemic chemotherapy followed by hepatic resection is the treatment of choice for patients with colorectal cancer liver metastasis (CRCLM) but reliable biomarkers predicting response to therapy are needed. Spontaneous apoptosis of single tumour cells is common in CRCLM. We explored the potential of circulating apoptosis markers to predict treatment response. Fifty-eight patients with CRCLM or hepatocellular carcinoma (HCC) were included in this study. Tumour tissue and blood samples were obtained before and after initiation of chemotherapy. Immunohistochemistry and ELISA assays were utilized to quantify the apoptosis marker caspase-cleaved cytokeratin 18 (M30) in tissue and circulation. CRCLM tissues showed more apoptotic tumour cells than HCC, or healthy liver. This was associated with elevated levels of circulating M30 (median = 244 U/l vs. 37 U/l in healthy controls, p = 0.009) which correlated with tumour volume (r2 = 0.92). Patients with progressive disease during chemotherapy showed higher M30 levels before therapy than responders (745 U/l vs. 136 U/l, p = 0.016). The predictive potential of M30 was higher than that of the tumour markers CA19-9 or CEA (AUC: 0.93, 0.63, and 0.78, respectively). Apoptotic tumour cells release cellular debris into the circulation, which provides information about tumour size and vitality. [ABSTRACT FROM AUTHOR]