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Circulating cell death products predict clinical outcome of colorectal cancer patients.

Koelink PJ, Lamers CB, Hommes DW, Verspaget HW - BMC Cancer (2009)

Bottom Line: Disease-free survival was determined using Kaplan-Meier methodology with Log Rank tests, and univariate and multivariate Cox proportional hazard analysis.The CK18-Asp396/CK18 ratio, which decreased with tumor progression, was also predictive of disease-free survival, with a low ratio (< or = median) associated with worse disease-free survival: HR 2.78 (95% CI: 1.06-7.19).CK18-Asp396 and total CK18 levels in the circulation of colorectal cancer patients are predictive of tumor progression and prognosis and might be helpful for treatment selection and monitoring of these patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Centre, C4-P, P,O, Box 9600, 2300 RC Leiden, The Netherlands. P.J.Koelink@lumc.nl

ABSTRACT

Background: Tumor cell death generates products that can be measured in the circulation of cancer patients. CK18-Asp396 (M30 antigen) is a caspase-degraded product of cytokeratin 18 (CK18), produced by apoptotic epithelial cells, and is elevated in breast and lung cancer patients.

Methods: We determined the CK18-Asp396 and total CK18 levels in plasma of 49 colorectal cancer patients, before and after surgical resection of the tumor, by ELISA. Correlations with patient and tumor characteristics were determined by Kruskal-Wallis H and Mann-Whitney U tests. Disease-free survival was determined using Kaplan-Meier methodology with Log Rank tests, and univariate and multivariate Cox proportional hazard analysis.

Results: Plasma CK18-Asp396 and total CK18 levels in colorectal cancer patients were related to disease stage and tumor diameter, and were predictive of disease-free survival, independent of disease-stage, with hazard ratios (HR) of patients with high levels (> median) compared to those with low levels (< or = median) of 3.58 (95% CI: 1.17-11.02) and 3.58 (95% CI: 0.97-7.71), respectively. The CK18-Asp396/CK18 ratio, which decreased with tumor progression, was also predictive of disease-free survival, with a low ratio (< or = median) associated with worse disease-free survival: HR 2.78 (95% CI: 1.06-7.19). Remarkably, the plasma CK18-Asp396 and total CK18 levels after surgical removal of the tumor were also predictive of disease-free survival, with patients with high levels having a HR of 3.78 (95% CI: 0.77-18.50) and 4.12 (95% CI: 0.84-20.34), respectively, indicating that these parameters can be used also to monitor patients after surgery.

Conclusion: CK18-Asp396 and total CK18 levels in the circulation of colorectal cancer patients are predictive of tumor progression and prognosis and might be helpful for treatment selection and monitoring of these patients.

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Pre-operative plasma CK18-Asp396 and total CK18 levels, and survival. CK18-Asp396 and total CK18 levels in pre-operative plasma of all colorectal cancer patients with a Dukes' A/B vs Dukes' C/D stage carcinoma (P1, A and B). Box plots with line indicating median value, box indicating IQR and bars indicating the range. Kaplan Meier disease-free survival curves of all colorectal cancer patients, groups divided upon median values of CK18-Asp396 (C) and total CK18 levels (D) in pre-operative plasma (P1). Patients were also subdivided in Dukes' A/B (E, n = 22) and Dukes' C/D (F, n = 27) stage carcinoma.
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Figure 1: Pre-operative plasma CK18-Asp396 and total CK18 levels, and survival. CK18-Asp396 and total CK18 levels in pre-operative plasma of all colorectal cancer patients with a Dukes' A/B vs Dukes' C/D stage carcinoma (P1, A and B). Box plots with line indicating median value, box indicating IQR and bars indicating the range. Kaplan Meier disease-free survival curves of all colorectal cancer patients, groups divided upon median values of CK18-Asp396 (C) and total CK18 levels (D) in pre-operative plasma (P1). Patients were also subdivided in Dukes' A/B (E, n = 22) and Dukes' C/D (F, n = 27) stage carcinoma.

Mentions: The clinico-pathological parameters of the 49 patients are shown in Table 2. CK18-Asp396 and total CK18 plasma levels did not correlate with localization of the tumor, also not within the patients with only colonic tumors (not shown). Male and female colorectal cancer patients had similar plasma CK18-Asp396 and total CK18 levels, and these were not correlated with patients' age. The CK18-Asp396 and total CK18 plasma values were higher in patients with more advanced tumor stages (Figure 1A and 1B, p = 0.01 and p = 0.05, respectively). CK18-Asp396 levels correlated with the diameter of the tumor (Spearman correlation coefficient Rho = 0.35, p = 0.02). Both CK18-Asp396 and total CK18 levels were significantly higher in the eight patients with a Dukes' D tumor in which the tumor was not (or not curatively) resected.


Circulating cell death products predict clinical outcome of colorectal cancer patients.

Koelink PJ, Lamers CB, Hommes DW, Verspaget HW - BMC Cancer (2009)

Pre-operative plasma CK18-Asp396 and total CK18 levels, and survival. CK18-Asp396 and total CK18 levels in pre-operative plasma of all colorectal cancer patients with a Dukes' A/B vs Dukes' C/D stage carcinoma (P1, A and B). Box plots with line indicating median value, box indicating IQR and bars indicating the range. Kaplan Meier disease-free survival curves of all colorectal cancer patients, groups divided upon median values of CK18-Asp396 (C) and total CK18 levels (D) in pre-operative plasma (P1). Patients were also subdivided in Dukes' A/B (E, n = 22) and Dukes' C/D (F, n = 27) stage carcinoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2666761&req=5

Figure 1: Pre-operative plasma CK18-Asp396 and total CK18 levels, and survival. CK18-Asp396 and total CK18 levels in pre-operative plasma of all colorectal cancer patients with a Dukes' A/B vs Dukes' C/D stage carcinoma (P1, A and B). Box plots with line indicating median value, box indicating IQR and bars indicating the range. Kaplan Meier disease-free survival curves of all colorectal cancer patients, groups divided upon median values of CK18-Asp396 (C) and total CK18 levels (D) in pre-operative plasma (P1). Patients were also subdivided in Dukes' A/B (E, n = 22) and Dukes' C/D (F, n = 27) stage carcinoma.
Mentions: The clinico-pathological parameters of the 49 patients are shown in Table 2. CK18-Asp396 and total CK18 plasma levels did not correlate with localization of the tumor, also not within the patients with only colonic tumors (not shown). Male and female colorectal cancer patients had similar plasma CK18-Asp396 and total CK18 levels, and these were not correlated with patients' age. The CK18-Asp396 and total CK18 plasma values were higher in patients with more advanced tumor stages (Figure 1A and 1B, p = 0.01 and p = 0.05, respectively). CK18-Asp396 levels correlated with the diameter of the tumor (Spearman correlation coefficient Rho = 0.35, p = 0.02). Both CK18-Asp396 and total CK18 levels were significantly higher in the eight patients with a Dukes' D tumor in which the tumor was not (or not curatively) resected.

Bottom Line: Disease-free survival was determined using Kaplan-Meier methodology with Log Rank tests, and univariate and multivariate Cox proportional hazard analysis.The CK18-Asp396/CK18 ratio, which decreased with tumor progression, was also predictive of disease-free survival, with a low ratio (< or = median) associated with worse disease-free survival: HR 2.78 (95% CI: 1.06-7.19).CK18-Asp396 and total CK18 levels in the circulation of colorectal cancer patients are predictive of tumor progression and prognosis and might be helpful for treatment selection and monitoring of these patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Centre, C4-P, P,O, Box 9600, 2300 RC Leiden, The Netherlands. P.J.Koelink@lumc.nl

ABSTRACT

Background: Tumor cell death generates products that can be measured in the circulation of cancer patients. CK18-Asp396 (M30 antigen) is a caspase-degraded product of cytokeratin 18 (CK18), produced by apoptotic epithelial cells, and is elevated in breast and lung cancer patients.

Methods: We determined the CK18-Asp396 and total CK18 levels in plasma of 49 colorectal cancer patients, before and after surgical resection of the tumor, by ELISA. Correlations with patient and tumor characteristics were determined by Kruskal-Wallis H and Mann-Whitney U tests. Disease-free survival was determined using Kaplan-Meier methodology with Log Rank tests, and univariate and multivariate Cox proportional hazard analysis.

Results: Plasma CK18-Asp396 and total CK18 levels in colorectal cancer patients were related to disease stage and tumor diameter, and were predictive of disease-free survival, independent of disease-stage, with hazard ratios (HR) of patients with high levels (> median) compared to those with low levels (< or = median) of 3.58 (95% CI: 1.17-11.02) and 3.58 (95% CI: 0.97-7.71), respectively. The CK18-Asp396/CK18 ratio, which decreased with tumor progression, was also predictive of disease-free survival, with a low ratio (< or = median) associated with worse disease-free survival: HR 2.78 (95% CI: 1.06-7.19). Remarkably, the plasma CK18-Asp396 and total CK18 levels after surgical removal of the tumor were also predictive of disease-free survival, with patients with high levels having a HR of 3.78 (95% CI: 0.77-18.50) and 4.12 (95% CI: 0.84-20.34), respectively, indicating that these parameters can be used also to monitor patients after surgery.

Conclusion: CK18-Asp396 and total CK18 levels in the circulation of colorectal cancer patients are predictive of tumor progression and prognosis and might be helpful for treatment selection and monitoring of these patients.

Show MeSH
Related in: MedlinePlus