Forthcoming prognostic markers for esophageal cancer: a systematic review and meta-analysis

Vinayak Nagaraja, Guy D. Eslick


Background: The incidence of esophageal cancer is rising, and survival rates remain poor. This metaanalysis summarizes five molecular mechanisms of disease progression, which are related to prognosis.
Patients and methods: A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google Scholar, Science Direct, and Web of Science. Original data was abstracted from each study and used to calculate a pooled event rate and 95% confidence interval (95% CI).
Results: Our analysis included five octamer-binding transcription factor 4 (OCT4) studies (564 patients), six sex determining region Y-box 2 (SOX2) studies (336 patients), five oestrogen receptor (ER) studies (367 patients), seven MET or MNNG HOS Transforming gene (c-Met) studies (1,015 patients) and six insulin like growth factor receptor studies (764 patients). Incidence of OCT4 in SCC was 53.60% (95% CI: 0.182-0.857) and the overall hazard ratio for poor clinic outcome was 2.9 (95% CI: 1.843-4.565). The incidence of SOX2 in SCC was 69.2% (95% CI: 0.361-0.899) however, was associated with significant heterogeneity of 90.94%. The prevalence of Oestrogen receptor α and β in SCC were 37.90% (95% CI: 0.317-0.444) and 67.20% (95% CI: 0.314-0.901) respectively. The prevalence of MET in EAC was 33.20% (95% CI: 0.031-0.884) and the incidence of insulin-like growth factor-1 receptor (IGF-1R) in EAC was 67.70% (95% CI: 0.333-0.898).
Conclusions: Our results show that the status of ER, OCT4 and SOX2 expression correlates with the unfavourable prognosis in patients with esophageal squamous cell carcinoma (ESCC). This study also highlights the potential impact of the IGF-1R on the biology of EAC and the expression of Met was recognised as a significant prognostic factor. Our data supports the concept of IGF axis, ER, Met, OCT4 and SOX2 inhibition as (neo-) adjuvant treatment.