High expression of GNB4 predicts poor prognosis in patients with Helicobacter pylori-positive advanced gastric cancer

BACKGROUND: Helicobacter pylori (H. pylori) is recognized as the most evident etiologic factor of infection-related gastric cancer (GC) and its involvement in GC initiation and progression has been well investigated. However, only a limited number of studies were performed to identify prognostic biomarkers and evaluate their clinical significance in GC patients infected with H. pylori. This study was conducted to investigate the clinical significance as well as its potential prognostic value of GNB4 in H. pylori-positive GC patients receiving standard treatment. METHODS: Retrospective statistical analysis was performed on 448 H. pylori-positive GC patients, with 137 early gastric cancer (EGC) patients undergoing radical gastrectomy alone and 311 advanced gastric cancer (AGC) patients receiving the same surgical procedure followed by fluorouracil-based chemotherapy. GNB4 expression was detected by immunohistochemistry staining on patient samples. H. pylori infection was routinely examined on endoscopic biopsy and/or surgical specimen of GC patients. RESULTS: High expression of GNB4 was 65.7% (90/137) in EGC and 62.7% (195/311) in AGC patients infected with H. pylori, respectively. In EGC patients, GNB4 expression was not associated with either clinicopathological parameters or 5-year overall survival (OS). In AGC patients however, high expression of GNB4 was significantly associated with patient’s pathological stage (P=0.047). Univariate analysis showed that tumor invasion depth (P=0.001), lymph node metastasis (P<0.001), pathological stage (P<0.001) as well as high expression of GNB4 (P=0.002) were significantly associated with 5-year OS. Multivariate analysis further identified lymph node metastasis (P=0.013) and GNB4 high expression (P=0.020) as independent prognostic factors for long-term outcome of H. pylori-positive AGC patients. CONCLUSIONS: This study demonstrates that high expression of GNB4 is significantly associated with pathological stage of AGC patients with H. pylori infection. GNB4 expression independently predicts the 5-year OS of H. pylori-positive AGC patients undergoing radical gastrectomy and adjuvant chemotherapy.