Prognostic and clinicopathological value of Ki-67 in patients with oesophageal squamous cell carcinoma: a systematic review and meta-analysis

Abstract

Objectives: The relationship between Ki-67 expression and the prognosis of patients with oesophageal squamous cell carcinoma (ESCC) has been extensively studied. However, their findings were inconsistent. Consequently, the present meta-analysis was performed to identify the precise value of Ki-67 in predicting the prognosis of ESCC.

Design: The current meta-analysis was carried out in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Data sources: Electronic databases of PubMed, Embase, Web of Science and Cochrane Library were systematically searched until 26 September 2023.

Statistical methods: Pooled HRs and corresponding 95% CIs were calculated to estimate the role of Ki-67 in predicting overall survival (OS) and disease-free survival (DFS) in ESCC. Between-study heterogeneity was evaluated using Cochrane's Q test and I² statistics. Specifically, significant heterogeneities were identified based on p<0.10 on the Q statistic test or I²>50% so the random-effects model should be used; otherwise, the fixed-effects model should be used. The relationship between Ki-67 and clinicopathological characteristics of ESCC was evaluated by combining ORs with their corresponding 95% CIs.

Results: 11 articles with 1124 patients were included in the present meta-analysis. Based on our analysis, increased Ki-67 expression was markedly associated with poor OS (HR 1.62, 95% CI 1.15 to 2.28, p=0.006) and DFS (HR 1.72, 95% CI 1.22 to 2.43, p=0.002) in ESCC. Moreover, subgroup analysis revealed that Ki-67 upregulation significantly predicted OS and DFS when a Ki-67 threshold of >30% was used. Nonetheless, Ki-67 was not significantly associated with sex, T stage, N stage, TNM stage, tumour differentiation or tumour location.

Conclusions: In the present meta-analysis, high Ki-67 expression significantly predicted OS and DFS in patients with ESCC, especially when Ki-67>30% was used as the threshold. These results suggest that Ki-67 could serve as an effective and reliable prognostic indicator for ESCC.

Keywords: Adult oncology; Adult pathology; EPIDEMIOLOGY; Gastrointestinal tumours; Meta-Analysis; Oesophageal disease.

Figure 1

The PRISMA flow chart of literature search and study selection. ESCC, oesophageal squamous cell carcinoma; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Figure 2

Forest plot of associations between Ki-67 expression and OS of ESCC patients. ESCC, oesophageal squamous cell carcinoma; OS, overall survival.

Figure 3

Forest plot of associations between Ki-67 expression and DFS of ESCC patients. DFS, disease-free survival; ESCC, oesophageal squamous cell carcinoma.

Figure 4

Forest plots of the relationship between Ki-67 expression and clinicopathological features of ESCC patients. (A) Gender (male vs female); (B) Differentiation (well/moderate vs poor); (C) T stage (T3+T4 vs T1+T2); (D) N stage (N1 vs N0); (E) TNM stage (III+IV vs I+II); and (F) Location (lower+mid-thorax vs upper). ESCC, oesophageal squamous cell carcinoma.

Figure 5

Sensitivity analysis. (A) OS and (B) DFS. DFS, disease-free survival; OS, overall survival.