Abstract
Except for excision repair cross-complementing 1 (ERCC1), mRNA expression of the remaining ERCC genes has not been investigated in the prognosis of gastric cancer (GC). The present study aimed to explore the mRNA expression and prognostic values of each member of the ERCC family in GC patients by using the Kaplan–Meier (KM) plotter tool. The details of each ERCC family member were entered into a database and GC patients were separated into high and low expression to draw survival plots using the KM plotter. In the present study, we observed that high expression of ERCC1 mRNA was significantly associated with longer overall survival (OS) for all GC patients (hazard ratio [HR]=0.77, 95% confidence intervals [CI]=0.63–0.95, P=0.016) compared with low expression. High expression of ERCC4 and ERCC6 mRNA indicated a worse OS for all GC patients (HR=1.28, 95% CI=1.02–1.6, P=0.035 and HR=1.25, 95% CI=1.02–1.54, P=0.029, respectively) and especially for patients with intestinal-type GC (HR=1.87, 95% CI=1.26–2.79, P=0.0018 and HR=1.62, 95% CI=1.04–2.54, P=0.033, respectively). High ERCC8 mRNA expression indicated a worse OS for all GC patients (HR=1.34, 95% CI=1.02–1.76, P=0.034) and especially for patients with diffuse-type GC (HR=2.25, 95% CI=1.36–3.75, P=0.0013). In conclusion, our findings indicate that ERCC4, ERCC6, and ERCC8 may be potential biomarkers for GC prognosis and may serve as potential therapeutic targets for GC. However, these findings still need further verification.
Highlights
Gastric cancer (GC) is the fifth most common malignancy and results in the third leading cause of cancer-associated mortality universally
A high expression of ERCC5 mRNA revealed a favorable overall survival (OS) for patients with diffuse-type gastric cancer (GC) (HR=0.56, 95% confidence intervals (CI)=0.31–1, P=0.048, Figure 8(c)), but ERCC5 had no impact on OS and the Lauren classification of GC patients (Figures 8(a), 8(b), and 8(d))
We evaluated the diagnostic role of ERCC6 mRNA expression (Affymetrix ID: 207347 at); high ERCC6 mRNA expression was associated with worse OS for all GC patients (HR=1.25, 95% CI=1.02–1.54, P=0.029, Figure 9(a)) and for those with intestinal-type GC (HR=1.62, 95% CI=1.04–2.54, P=0.033, Figure 9(b)), but there was no significant correlation with better or worse OS for patients with diffuse and mixedtype GC (Figures 9(c) and 9(d))
Summary
Gastric cancer (GC) is the fifth most common malignancy and results in the third leading cause of cancer-associated mortality universally. It was reported that a polymorphism of ERCC2 was associated with a reduced response to chemotherapy and overall survival (OS) in GC patients receiving oxaliplatin treatment [7]. The KM plotter is able to evaluate the effect of 54,675 genes on survival using 10,461 cancer samples It includes 5,143 breast cancer, 1,816 ovarian cancer, 2,437 lung cancer, and 1,065 GC patients with a mean follow-up of 69 months. The KM plotter is broadly used for the analysis of the clinical impact of individual genes on survival time in cancer patients, including GC. We explored the mRNA expression and prognostic values of each member of the ERCC family in human GC patients via the KM plotter database
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