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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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Post-operative CK18-Asp396, total CK18 and CK18-Asp396/CK18 ratios levels, and survival. Post-operative (P3) CK18-Asp396 and total CK18 levels of colorectal cancer patients with a Dukes' A/B vs Dukes' C/D stage carcinoma (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 post-operative CK18-Asp396 (C, n = 28) and total CK18 levels (D, n = 28). Plasma CK18-Asp396/CK18 ratios were decreased in patients Dukes' C/D vs Dukes' A/B (E). Kaplan Meier disease-free survival curves of colorectal cancer patients, groups divided upon median post-operative plasma CK18-Asp396/CK18 ratios (F, n = 28).
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Figure 3: Post-operative CK18-Asp396, total CK18 and CK18-Asp396/CK18 ratios levels, and survival. Post-operative (P3) CK18-Asp396 and total CK18 levels of colorectal cancer patients with a Dukes' A/B vs Dukes' C/D stage carcinoma (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 post-operative CK18-Asp396 (C, n = 28) and total CK18 levels (D, n = 28). Plasma CK18-Asp396/CK18 ratios were decreased in patients Dukes' C/D vs Dukes' A/B (E). Kaplan Meier disease-free survival curves of colorectal cancer patients, groups divided upon median post-operative plasma CK18-Asp396/CK18 ratios (F, n = 28).

Mentions: Post-operative plasma CK18-Asp396 levels of patients about 4.5 months after resection of Dukes' C/D stage carcinomas were also somewhat, but not significantly, higher compared with patients with Dukes' A/B stage carcinomas (Figure 3A). The total CK18 plasma levels, however, were significantly higher in Dukes' C/D tumor patients compared with Dukes' A/B tumor patients (Figure 3B). High CK18-Asp396 levels as well as total CK18 plasma levels after tumor resection were associated with worse disease-free survival (Figure 3C and 3D), also found in the univariate Cox hazard analysis (Table 3).


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

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

Post-operative CK18-Asp396, total CK18 and CK18-Asp396/CK18 ratios levels, and survival. Post-operative (P3) CK18-Asp396 and total CK18 levels of colorectal cancer patients with a Dukes' A/B vs Dukes' C/D stage carcinoma (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 post-operative CK18-Asp396 (C, n = 28) and total CK18 levels (D, n = 28). Plasma CK18-Asp396/CK18 ratios were decreased in patients Dukes' C/D vs Dukes' A/B (E). Kaplan Meier disease-free survival curves of colorectal cancer patients, groups divided upon median post-operative plasma CK18-Asp396/CK18 ratios (F, n = 28).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Post-operative CK18-Asp396, total CK18 and CK18-Asp396/CK18 ratios levels, and survival. Post-operative (P3) CK18-Asp396 and total CK18 levels of colorectal cancer patients with a Dukes' A/B vs Dukes' C/D stage carcinoma (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 post-operative CK18-Asp396 (C, n = 28) and total CK18 levels (D, n = 28). Plasma CK18-Asp396/CK18 ratios were decreased in patients Dukes' C/D vs Dukes' A/B (E). Kaplan Meier disease-free survival curves of colorectal cancer patients, groups divided upon median post-operative plasma CK18-Asp396/CK18 ratios (F, n = 28).
Mentions: Post-operative plasma CK18-Asp396 levels of patients about 4.5 months after resection of Dukes' C/D stage carcinomas were also somewhat, but not significantly, higher compared with patients with Dukes' A/B stage carcinomas (Figure 3A). The total CK18 plasma levels, however, were significantly higher in Dukes' C/D tumor patients compared with Dukes' A/B tumor patients (Figure 3B). High CK18-Asp396 levels as well as total CK18 plasma levels after tumor resection were associated with worse disease-free survival (Figure 3C and 3D), also found in the univariate Cox hazard analysis (Table 3).

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