High Expression of Growth Factor Receptor-bound Protein 14 Predicts Clinical Progression and Poor Prognosis in Patients with Lung Adenocarcinoma

Background: Growth factor receptor-bound protein 14 (Grb14) is an adaptor molecule of the Grb7/10/14 family with a characteristic “between PH and SH2” (BPS) domain that serves to tightly bind tyrosine kinases. Previous studies have demonstrated that Grb14 upregulation may be used as a marker of proliferation, invasion and malignant cell growth in tumors. The overexpression of Grb14 has also been reported to be associated with a poor prognosis in cancer patients. However, the clinical significance of Grb14 in lung adenocarcinoma has not yet been fully elucidated.Methods: Grb14 protein expression in human lung adenocarcinoma and noncancerous lung tissues was detected by immunohistochemistry analyses. Then, the associations of Grb14 expression with clinicopathological features and clinical outcomes of lung cancer patients were validated by analyzing a microarray-based TCGA dataset at the mRNA level and statistically evaluating the results.Results: Immunohistochemistry and dataset analyses revealed that Grb14 expression was significantly increased in lung adenocarcinoma tissues compared with noncancerous lung tissues [immunoreactivity score (IRS): lung adenocarcinoma, 6.07±1.01 vs benign, 4.80±1.22, P<0.001]. Additionally, as revealed by analysis of the dataset, the upregulation of Grb14 mRNA expression in the lung adenocarcinoma tissues was significantly correlated with poor overall survival (P<0.001). Furthermore, univariate analysis revealed that higher pathological stage [hazard ratio (HR), 1.925, 95% CI, 0.912-6.301; P<0.05], higher tumor stage (HR, 2.436, 95% CI, 1.659-5.551; P<0.001), higher surgical margin resection status (HR, 3.035, 95% CI, 1.305-37.51; P<0.01) and prior diagnosis status (HR, 0.4893, 95% CI, 0.1818-0.8197; P<0.01) were independent predictors for a shorter survival. Multivariate analysis also revealed that higher pathological stage (HR, 3.730, 95% CI, 1.784-7.796; P<0.01), higher surgical margin resection status (HR, 6.914, 95% CI, 2.063-23.171; P<0.01) and prior diagnosis status were related to a shorter survival. Conclusion: Our data suggest that elevated Grb14 expression plays an important role in the progression of lung adenocarcinoma. More importantly, the increased expression of Grb14 may efficiently predict poor survival in lung adenocarcinoma patients.