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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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Meta-analysis plots of the progression-free and overall survival hazard ratios in individual trials.A is the forest plot and B, C, and D are the “filled” funnel plots of OS, DFS, and the unclear group, respectively. The meta-analysis displayed a significant effect in favor of a high volume. The pooled and filled results are presented in Table 2.
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pone-0103910-g004: Meta-analysis plots of the progression-free and overall survival hazard ratios in individual trials.A is the forest plot and B, C, and D are the “filled” funnel plots of OS, DFS, and the unclear group, respectively. The meta-analysis displayed a significant effect in favor of a high volume. The pooled and filled results are presented in Table 2.

Mentions: The most frequently reported prognostic marker for CRC is CEA. The CEA studies included 5792 patients, of which 3856 patients had positive results for the CEA marker, whereas 1936 patients were negative. The cut-off values ranged from 2.7 ng/ml to 10.0 ng/ml. The median patient age across all trials was between 47.74 and 73 years, with an age range of 31—90 years. All patients had histologically or cytologically confirmed CRC, colon or rectal cancer, as the primary diagnosis. There are 28 articles related to CEA and the prognosis outcome of the patients, of which 6 articles studied both the overall survival (OS) and disease-free survival (DFS). There are 9 articles that do not state whether they studied the OS or DFS; we defined these as “unclear” (Table 2). A summary of the individual trials and overall pooled results from the primary analysis of the overall survival is shown in Figure 4. According to the outcomes (OS, DFS and unclear), the CEA was classified into three subgroups, and the three subgroup datasets were separately submitted to the meta-analysis and publication bias analysis. As a result, the pooled HRs with 95% CIs of OS, DFS, and unclear subgroups were 1.624 (1.290–2.043), 1.453 (1.267–1.666), and 2.208 (1.479–3.297), respectively, and the overall HR (CI) from the three combined subgroups was 1.513 (1.391–1.645) (Figure 4 A). After analysis of the publication bias by the “trim and fill” method, the OS, DFS, and unclear subgroups were added with three, seven, and one “missing” studies (Figure 4 B C and D and Table 2), respectively. The adjusted HRs with the 95% CIs for the three subgroups were 1.346 (1.083–1.671), 1.166 (1.018–1.336) and 2.073 (1.410–3.047), respectively. In contrast, all adjusted HRs were relatively smaller than the unadjusted HRs (Table 2, panel CEA). Likewise, the same methods of meta-analysis and publication bias analysis were implemented for the remaining prognostic markers with more than three repetitions in studies on CRC. The results are shown in Table 2, and the characteristics of those makers are listed Table S5. The corresponding Forest plots and funnel plots are shown Appendix 8 in Materials S1.


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)

Meta-analysis plots of the progression-free and overall survival hazard ratios in individual trials.A is the forest plot and B, C, and D are the “filled” funnel plots of OS, DFS, and the unclear group, respectively. The meta-analysis displayed a significant effect in favor of a high volume. The pooled and filled results are presented in Table 2.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0103910-g004: Meta-analysis plots of the progression-free and overall survival hazard ratios in individual trials.A is the forest plot and B, C, and D are the “filled” funnel plots of OS, DFS, and the unclear group, respectively. The meta-analysis displayed a significant effect in favor of a high volume. The pooled and filled results are presented in Table 2.
Mentions: The most frequently reported prognostic marker for CRC is CEA. The CEA studies included 5792 patients, of which 3856 patients had positive results for the CEA marker, whereas 1936 patients were negative. The cut-off values ranged from 2.7 ng/ml to 10.0 ng/ml. The median patient age across all trials was between 47.74 and 73 years, with an age range of 31—90 years. All patients had histologically or cytologically confirmed CRC, colon or rectal cancer, as the primary diagnosis. There are 28 articles related to CEA and the prognosis outcome of the patients, of which 6 articles studied both the overall survival (OS) and disease-free survival (DFS). There are 9 articles that do not state whether they studied the OS or DFS; we defined these as “unclear” (Table 2). A summary of the individual trials and overall pooled results from the primary analysis of the overall survival is shown in Figure 4. According to the outcomes (OS, DFS and unclear), the CEA was classified into three subgroups, and the three subgroup datasets were separately submitted to the meta-analysis and publication bias analysis. As a result, the pooled HRs with 95% CIs of OS, DFS, and unclear subgroups were 1.624 (1.290–2.043), 1.453 (1.267–1.666), and 2.208 (1.479–3.297), respectively, and the overall HR (CI) from the three combined subgroups was 1.513 (1.391–1.645) (Figure 4 A). After analysis of the publication bias by the “trim and fill” method, the OS, DFS, and unclear subgroups were added with three, seven, and one “missing” studies (Figure 4 B C and D and Table 2), respectively. The adjusted HRs with the 95% CIs for the three subgroups were 1.346 (1.083–1.671), 1.166 (1.018–1.336) and 2.073 (1.410–3.047), respectively. In contrast, all adjusted HRs were relatively smaller than the unadjusted HRs (Table 2, panel CEA). Likewise, the same methods of meta-analysis and publication bias analysis were implemented for the remaining prognostic markers with more than three repetitions in studies on CRC. The results are shown in Table 2, and the characteristics of those makers are listed Table S5. The corresponding Forest plots and funnel plots are shown Appendix 8 in Materials S1.

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