Abstract
BackgroundRecent studies have demonstrated that the kallikrein and kallikrein-related peptidases (KLKs) exhibit aberrant expression in patients with colorectal cancer (CRC) and might be considered as potential prognostic biomarkers of CRC. However, inconsistent findings have been reported, which promote us to summarize the global prognostic roles of KLKs for survival in CRC patients.MethodsEligible published studies were identified by searching electronic databases with several search strategies. The patients’ baseline characteristics and survival results were extracted from enrolled studies and pooled as combined hazard ratio (HR) with 95% confidence interval (95% CI) to estimate the effect size.ResultsA total of 25 and 22 eligible studies were included in the meta-analysis to evaluate the prognostic roles of KLKs on overall survival (OS) and disease-free survival (DFS), respectively. KLKs overexpression was significantly associated with worse OS (pooled HR = 1.43, 95% CI 1.27–1.60, P < 0.001) and short DFS (pooled HR = 1.35, 95% CI 1.21–1.51, P < 0.001). Importantly, subgroup and meta-regression analyses revealed the survival differences among different races and detection methods of KLKs. Furthermore, several specific members of KLKs were identified to be more significantly related to worse OS and DFS compared with other members.ConclusionThe present study demonstrated that KLKs may have the potential to serve as promising biomarkers to monitor CRC prognosis and progression. The promising results concerning the utility of KLKs in clinical practice encourage the further investigation of their clinical utility applicability as tumor markers of CRC.
Highlights
Recent studies have demonstrated that the kallikrein and kallikrein-related peptidases (KLKs) exhibit aberrant expression in patients with colorectal cancer (CRC) and might be considered as potential prognostic biomarkers of CRC
As shown in the flow diagram for the literature (Fig. 1), after careful exclusion of inappropriate ones in each step, 14 articles including 25 studies for overall survival (OS) and 22 studies for disease-free survival (DFS) that met the inclusion norm were enrolled for the evidence synthesis, which evaluated the relevance between KLKs expression and CRC prognosis [8, 9, 15,16,17,18,19,20,21,22,23,24,25]
The results suggested that the associations between KLKs overexpression and worse DFS were significant in Caucasian patients, and more pronounced in Asian
Summary
Recent studies have demonstrated that the kallikrein and kallikrein-related peptidases (KLKs) exhibit aberrant expression in patients with colorectal cancer (CRC) and might be considered as potential prognostic biomarkers of CRC. Protein expression analysis of a panel of KLKs in cytosolic extracts from CRC tissues revealed that KLKs are aberrantly expressed in colorectal tumors, compared with their noncancerous counterparts [7]. Given their critical involvement in the vital biological processes and unique biomarker features mentioned above, KLKs could be considered as good candidates in increasing the accuracy of prediction of patients’ survival beyond the traditional clinical information
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