Reduced NM23 Protein Level Correlates With Worse Clinicopathologic Features in Colorectal Cancers: A Meta-Analysis of Pooled Data

Abstract

The clinical value of a prominent metastasis suppressor, nonmetastatic protein 23 (NM23), remains controversial. In this study, we examined the correlation between NM23 protein levels and the clinicopathologic features of colorectal cancers (CRC), and assessed the overall prognostic value of NM23 for CRC. Embase, PubMed, Web of Science, and other scientific literature databases were exhaustively searched to identify relevant studies published prior to June 31, 2015. The methodological qualities of selected studies were scored based on the critical appraisal skills program (CASP) criteria, as independently assessed by 2 reviewers. NM23 protein levels in tumor tissues of CRC patients were examined in relation to Dukes stage, differentiation grade, T-stage, lymph node metastasis status, and overall survival (OS). STATA software version 12.0 (Stata Corp, College Station, TX) was used for statistical analysis of data pooled from selected studies. Nineteen cohort studies met the inclusion criteria for present study and contained a combined total of 2148 study subjects. Pooled odd ratios (ORs) for NM23 expression revealed that reduced NM23 protein levels in CRC tumor tissues correlated with Dukes stage C and D (OR = 1.89, 95% CI: 1.06-3.39, P = 0.032), poor differentiation grades (OR = 1.41, 95% CI: 1.03-1.94, P = 0.032), and positive lymph node metastasis status (OR = 3.21, 95% CI: 1.95-5.29, P < 0.001). On the other hand, no such correlations were evident with T-stage T3-4 (OR = 1.56, 95% CI: 0.60-4.06, P = 0.367) or OS (OR = 0.79, 95% CI: 0.58-1.08, P = 0.138). Our analysis of pooled data found that NM23 expression is reduced in CRC tissues and low NM23 levels tightly correlate with higher Dukes stages, poorer differentiation grade, and positive lymph node metastases. However, NM23 levels did not influence the OS in CRC patients.

FIGURE 1

Flowchart illustrating the study search strategy and study selection. Nineteen cohort studies were eventually incorporated in this meta-analysis.

FIGURE 2

Risk of publication bias summary: review authors’ judgements about each risk of bias item for each included study.

FIGURE 3

Forest plots based on odd ratios with 95% confidence interval of individual studies and pooled data detailing the association of the NM23 expression with the clinicopathological features and prognosis of colorectal cancer patients in overall analysis.

FIGURE 4

Ethnic-stratified subgroup analysis investigating the effect of the NM23 expression on colorectal cancer.

FIGURE 5

Sensitivity analysis to investigate the association of NM23 expression and colorectal cancer clinicopathological features and prognosis.

FIGURE 6

Publication biases detection to examine the relationship between NM23 expression and colorectal cancer, which highlighted the lack of publication bias and supports the credibility of the results.