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A systematic review and meta-analysis of diagnostic and prognostic serum biomarkers of colorectal cancer.

Liu Z, Zhang Y, Niu Y, Li K, Liu X, Chen H, Gao C - PLoS ONE (2014)

Bottom Line: The databases MEDLINE and EMBASE were searched iteratively to identify the relevant literature for serum markers of CRC published from 1950 to August 2012.All of the pooled sensitivities of the diagnostic markers with > = 3 repetitions were less than 50%, and the meta-analyses of the prognostic markers with more than 3 studies were performed, VEGF with highest (2.245, CI: 1.347-3.744) and MMP-7 with lowest (1.099, CI: 1.018-1.187)) pooled HRs are presented.The poor characteristics indicate that these tests are of little value for clinical practice.

View Article: PubMed Central - PubMed

Affiliation: Anal-Colorectal Surgery Institute, Central Hospital of PLA, Luoyang, Henan, China.

ABSTRACT

Background: Our systematic review summarizes the evidence concerning the accuracy of serum diagnostic and prognostic tests for colorectal cancer (CRC).

Methods: The databases MEDLINE and EMBASE were searched iteratively to identify the relevant literature for serum markers of CRC published from 1950 to August 2012. The articles that provided adequate information to meet the requirements of the meta-analysis of diagnostic and prognostic markers were included. A 2-by-2 table of each diagnostic marker and its hazard ratio (HR) and the confidence interval (CI) of each prognostic marker was directly or indirectly extracted from the included papers, and the pooled sensitivity and specificity of the diagnostic marker and the pooled HR and the CI of the prognostic marker were subsequently calculated using the extracted data.

Results: In total, 104 papers related to the diagnostic markers and 49 papers related to the prognostic serum markers of CRC were collected, and only 19 of 92 diagnostic markers were investigated in more than two studies, whereas 21 out of 44 prognostic markers were included in two or more studies. All of the pooled sensitivities of the diagnostic markers with > = 3 repetitions were less than 50%, and the meta-analyses of the prognostic markers with more than 3 studies were performed, VEGF with highest (2.245, CI: 1.347-3.744) and MMP-7 with lowest (1.099, CI: 1.018-1.187)) pooled HRs are presented.

Conclusions: The quality of studies addressing the diagnostic and prognostic accuracy of the tests was poor, and the results were highly heterogeneous. The poor characteristics indicate that these tests are of little value for clinical practice.

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Related in: MedlinePlus

The ROC and forest plots of summary estimates of sensitivity and specificity of diagnostic marker CEA.A is the ROC plot of the hierarchical summary estimates of sensitivity and specificity for CEA with 95% confidence and prediction ellipses. B and C are forest plots of sensitivity and specificity of the diagnostic marker CEA for colorectal cancer plotted with a HSROC model. The size of the squares in B and C are proportional to the study size and weight for each study. The rhombus represents the pooled estimates, which are 0.461 (CI: 0.448–0.474) and 0.892 (CI: 0.882–0.902) for specificity and sensitivity, respectively.
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pone-0103910-g003: The ROC and forest plots of summary estimates of sensitivity and specificity of diagnostic marker CEA.A is the ROC plot of the hierarchical summary estimates of sensitivity and specificity for CEA with 95% confidence and prediction ellipses. B and C are forest plots of sensitivity and specificity of the diagnostic marker CEA for colorectal cancer plotted with a HSROC model. The size of the squares in B and C are proportional to the study size and weight for each study. The rhombus represents the pooled estimates, which are 0.461 (CI: 0.448–0.474) and 0.892 (CI: 0.882–0.902) for specificity and sensitivity, respectively.

Mentions: Figure 3 A presents hierarchical summary estimates of sensitivity and specificity for CEA after back-transformation to ROC axes. Furthermore, it shows the 95% confidence ellipse around the mean values of sensitivity and specificity for CEA and a 95% prediction ellipse for the individual values of sensitivity and specificity. The ellipse around the summary or mean estimate of sensitivity and specificity marks the region containing likely combinations for which the mean value of sensitivity and specificity is small. The 95% prediction ellipse is wider and indicates more uncertainty as to where the likely values of sensitivity and specificity might occur for individual studies. Figures 3 B and C separately present the forest plots of the specificity and sensitivity of the diagnostic marker CEA for colorectal cancer with individual study estimates of the sensitivities and specificities and the 95% CIs as a random-effects model. The simple summary estimates of the sensitivity and specificity of CEA for colorectal cancer were 46.1% (95% CI: 44.8–47.4%) and 89.2% (95% CI: 88.2–90.2%), respectively. The HSROC model produced the same summary estimates of sensitivity and specificity with almost exactly equal CIs (48.5% (95% CI: 44.8–52.3–46.7%) and 91.1% (95% CI: 88–93.0%), respectively) that take into account the heterogeneity beyond chance between studies (random-effects model). For the remaining serum markers for CRC, the pooled sensitivities and specificities with their CIs are, respectively, listed in the 6th and 7th columns in Table 1, but the HSROC plots and forest plots are presented in Appendix 6 in Materials S1 because of article length limits. Publication bias analyses were implemented for the prognostic markers with more than three repetitions in studies. The results are shown in the 12th–15th column in Table 1, and the characteristics of those makers are listed in Table S3. The corresponding forest plots and funnel plots are shown Appendix 7 in Materials S1. The results indicate that the publication bias exist for almost all diagnostic markers.


A systematic review and meta-analysis of diagnostic and prognostic serum biomarkers of colorectal cancer.

Liu Z, Zhang Y, Niu Y, Li K, Liu X, Chen H, Gao C - PLoS ONE (2014)

The ROC and forest plots of summary estimates of sensitivity and specificity of diagnostic marker CEA.A is the ROC plot of the hierarchical summary estimates of sensitivity and specificity for CEA with 95% confidence and prediction ellipses. B and C are forest plots of sensitivity and specificity of the diagnostic marker CEA for colorectal cancer plotted with a HSROC model. The size of the squares in B and C are proportional to the study size and weight for each study. The rhombus represents the pooled estimates, which are 0.461 (CI: 0.448–0.474) and 0.892 (CI: 0.882–0.902) for specificity and sensitivity, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126674&req=5

pone-0103910-g003: The ROC and forest plots of summary estimates of sensitivity and specificity of diagnostic marker CEA.A is the ROC plot of the hierarchical summary estimates of sensitivity and specificity for CEA with 95% confidence and prediction ellipses. B and C are forest plots of sensitivity and specificity of the diagnostic marker CEA for colorectal cancer plotted with a HSROC model. The size of the squares in B and C are proportional to the study size and weight for each study. The rhombus represents the pooled estimates, which are 0.461 (CI: 0.448–0.474) and 0.892 (CI: 0.882–0.902) for specificity and sensitivity, respectively.
Mentions: Figure 3 A presents hierarchical summary estimates of sensitivity and specificity for CEA after back-transformation to ROC axes. Furthermore, it shows the 95% confidence ellipse around the mean values of sensitivity and specificity for CEA and a 95% prediction ellipse for the individual values of sensitivity and specificity. The ellipse around the summary or mean estimate of sensitivity and specificity marks the region containing likely combinations for which the mean value of sensitivity and specificity is small. The 95% prediction ellipse is wider and indicates more uncertainty as to where the likely values of sensitivity and specificity might occur for individual studies. Figures 3 B and C separately present the forest plots of the specificity and sensitivity of the diagnostic marker CEA for colorectal cancer with individual study estimates of the sensitivities and specificities and the 95% CIs as a random-effects model. The simple summary estimates of the sensitivity and specificity of CEA for colorectal cancer were 46.1% (95% CI: 44.8–47.4%) and 89.2% (95% CI: 88.2–90.2%), respectively. The HSROC model produced the same summary estimates of sensitivity and specificity with almost exactly equal CIs (48.5% (95% CI: 44.8–52.3–46.7%) and 91.1% (95% CI: 88–93.0%), respectively) that take into account the heterogeneity beyond chance between studies (random-effects model). For the remaining serum markers for CRC, the pooled sensitivities and specificities with their CIs are, respectively, listed in the 6th and 7th columns in Table 1, but the HSROC plots and forest plots are presented in Appendix 6 in Materials S1 because of article length limits. Publication bias analyses were implemented for the prognostic markers with more than three repetitions in studies. The results are shown in the 12th–15th column in Table 1, and the characteristics of those makers are listed in Table S3. The corresponding forest plots and funnel plots are shown Appendix 7 in Materials S1. The results indicate that the publication bias exist for almost all diagnostic markers.

Bottom Line: The databases MEDLINE and EMBASE were searched iteratively to identify the relevant literature for serum markers of CRC published from 1950 to August 2012.All of the pooled sensitivities of the diagnostic markers with > = 3 repetitions were less than 50%, and the meta-analyses of the prognostic markers with more than 3 studies were performed, VEGF with highest (2.245, CI: 1.347-3.744) and MMP-7 with lowest (1.099, CI: 1.018-1.187)) pooled HRs are presented.The poor characteristics indicate that these tests are of little value for clinical practice.

View Article: PubMed Central - PubMed

Affiliation: Anal-Colorectal Surgery Institute, Central Hospital of PLA, Luoyang, Henan, China.

ABSTRACT

Background: Our systematic review summarizes the evidence concerning the accuracy of serum diagnostic and prognostic tests for colorectal cancer (CRC).

Methods: The databases MEDLINE and EMBASE were searched iteratively to identify the relevant literature for serum markers of CRC published from 1950 to August 2012. The articles that provided adequate information to meet the requirements of the meta-analysis of diagnostic and prognostic markers were included. A 2-by-2 table of each diagnostic marker and its hazard ratio (HR) and the confidence interval (CI) of each prognostic marker was directly or indirectly extracted from the included papers, and the pooled sensitivity and specificity of the diagnostic marker and the pooled HR and the CI of the prognostic marker were subsequently calculated using the extracted data.

Results: In total, 104 papers related to the diagnostic markers and 49 papers related to the prognostic serum markers of CRC were collected, and only 19 of 92 diagnostic markers were investigated in more than two studies, whereas 21 out of 44 prognostic markers were included in two or more studies. All of the pooled sensitivities of the diagnostic markers with > = 3 repetitions were less than 50%, and the meta-analyses of the prognostic markers with more than 3 studies were performed, VEGF with highest (2.245, CI: 1.347-3.744) and MMP-7 with lowest (1.099, CI: 1.018-1.187)) pooled HRs are presented.

Conclusions: The quality of studies addressing the diagnostic and prognostic accuracy of the tests was poor, and the results were highly heterogeneous. The poor characteristics indicate that these tests are of little value for clinical practice.

Show MeSH
Related in: MedlinePlus