Cytokeratin 18 in plasma of patients with gastrointestinal adenocarcinoma as a biomarker of tumour response

Abstract

BACKGROUND: Plasma biomarkers may be particularly useful as a predictor or early marker of clinical response to treatment in addition to radiological imaging. Cytokeratin 18 (CK18) is an epithelial-specific cytokeratin that undergoes cleavage by caspases during apoptosis. Measurement of caspase-cleaved (CK18 -Asp396) or total cytokeratin 18 (CK18) from epithelial-derived tumours could be a simple, non-invasive way to monitor or predict responses to treatment. METHODS: Soluble plasma CK18 -Asp396 and CK18 were measured by ELISA from 73 patients with advanced gastrointestinal adenocarcinomas before treatment and during chemotherapy, as well as 100 healthy volunteers. RESULTS: Both CK18 -Asp396 and total CK18 plasma levels were significantly higher in patients compared with the healthy volunteers (P ¼ 0.015, Po0.001). The total CK18 baseline plasma levels before treatment were significantly higher (P ¼ 0.009) in patients who develop progressive disease than those who achieve partial response or stable disease and this correlation was confirmed in an independent validation set. The peak plasma levels of CK18 occurring in any cycle following treatment were also found to be associated with tumour response, but peak levels of CK18 -Asp396 did not reach significance (P ¼ 0.01, and P ¼ 0.07, respectively). CONCLUSION: Plasma levels CK18 are a potential marker of tumour response in patients with advanced gastrointestinal malignancy.

Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer

“…Studies on specific tumour types include lung (Ulukaya et al, 2007;Hou et al, 2009), breast (Olofsson et al, 2007, prostate (Kramer et al, 2006), head and neck (Ozturk et al, 2009), colorectal (Ausch et al, 2009Koelink et al, 2009) and testicular (de Haas et al, 2008) tumours. Although a recent study concluded that plasma levels of CK18 are a potential marker of tumour response in patients with advanced gastrointestinal malignancy (Scott et al, 2009) no previous studies have been reported in patients with pancreatic cancer.The objective of this study was to characterise the baseline levels of circulating plasma CK18 concentrations using both the M65 and M30 ELISA assays in patients with pancreatic cancer. Correlations were also examined between CK18 and the circulating levels of carbohydrate antigen 19-9 (CA19-9), the only widely used biomarker in pancreatic cancer (Smith et al, 2008).…”

Serum cytokeratin 18 as a biomarker for gastric cancer

“…and M65 levels were also increased in patients with advanced gastrointestinal adenocarcinoma [2,25]. Yaman E et al reported that serum M30 and M65 levels were increased in patients with advanced gastric cancer, and only M30 levels reflected the tumor load [26].…”

“…Moreover, M65 and M30 levels reflect chemotherapy-induced changes in testicular germ cell cancer [21]. CK18 levels before initiation of chemotherapy may be 17 an indicator of tumor response to the chemotherapy in patients with advanced gastrointestinal adenocarcinomas [2]. On the other hand, the levels of M30 were increased during chemotherapy in patients with gastrointestinal cancer, which was also related with response to the therapy [25].…”

“…However, the biomarkers currently available for the management of solid tumors do not fulfill all the above criteria and, therefore, are not presently recommended for screening of the general population [2].…”

“…This assay can be used clinically for patients with several epithelial cancers such as head and neck tumors, endometrial carcinoma, testicular cancer, prostate cancer, breast cancer, lung cancer, colorectal cancer, and pancreatic cancer [18][19][20][21][22][23][24]. In addition, serum levels of M30 and M65 are increased in patients with advanced gastrointestinal adenocarcinoma [2,25]. Recently, increased serum levels of M30 and M65 have been reported in patients with advanced gastric cancer [26].…”