Prognostic and clinicopathological significance of survivin in colorectal cancer: a meta-analysis

Abstract

Survivin/BIRC5 is a potentially interesting prognostic marker and therapeutic target in colorectal cancer (CRC). However, the available data on survivin expression in CRC are heterogeneous. Thus, to clarify the prognostic relevance of survivin in patients with CRC and its association with clinicopathological parameters we performed a meta-analysis. We screened PubMed and EMBASE for those studies that investigated the prognostic value of survivin and its association with clinicopathological parameters in CRC. Data from eligible studies were extracted and included into the meta-analyses using a random effects model. Electronical literature search identified 15 studies including 1934 patients with CRC mostly detecting survivin by immunohistochemistry (IHC). Pooled hazard ratios of 11 studies that performed survival analysis revealed a positive correlation between survivin expression and poor prognosis (HR 1.93; 95% CI: 1.55-2.42; P<0.00001; I(2) = 23%). Subgroup analyses with respect to the detection method, HR estimation, global quality score and the country of origin in which the study was conducted supported the stability of this observation. In addition, meta-analyses revealed a significant association between expression of survivin and the presence of lymph node metastases (OR: 0.37; 95% CI: 0.19-0.75; I(2) = 61%) or blood vessel invasion (OR: 0.50; 95% CI: 0.28-0.90; I(2) = 0%). Expression of survivin indicates poor prognosis and a pro-metastatic phenotype and may be useful in identifying a subgroup of patients that could benefit from a targeted therapy against survivin in CRC.

Figure 1. Flow chart summarising the literature search and study selection.

Figure 2. Meta-analysis comparing survivin expression and overall survival in CRC patients.

(A) Forest blot reflects the individual and pooled HR with CI. Heterogeneity was calculated by the Cochrane Q test (Chi-squared test; Chi²) and by measuring the inconsistency (I²). (B) Funnel blot was designed to visualize a potential publication bias.

Figure 3. Association between survivin and lymph node metastasis or blood vessel invasion.

Forest blot reflects the individual summarized OR with CI for the relationship between expression of survivin and (A) lymph node metastasis or (B) blood vessel invasion. Heterogeneity was verified by the Cochrane Q test (Chi-squared test; Chi²) and inconsistency (I²).