The Prognostic and Functional Impact of Sprouty 2 Expression in Non–small Cell Lung Cancer

Abstract

Objective: We represent Sprouty 2 (Spry2) expression analysis and its association with key driver mutations and clinical features of patients with non–small cell lung cancer as the largest ex vivo data. Methods: The strength of Spry2 expression was evaluated using the immunoreactivity score (IRS), which was calculated using the following formula: IRS=(staining intensity score) SI×(percentage of positively stained cells) PP. The median IRS score was defined as the cutoff value. Patients were grouped as “weak immunoreactivity score” (IRS: 0 to 4) or “strong immunoreactivity score” (IRS: ≥4) with respect to the IRS score. Results: The intensity and percentage of Spry2 staining were significantly lower in tumor tissues than in normal lung tissues (P<0.0001). Patients’ characteristics were similar for both groups, except for smoking status and, brain and lymph node metastasis. Overall survival of patients with a strong immunoreactivity score was significantly lower than those with a weak immunoreactivity score among metastatic patients (6.9 mo vs. 13.6, P=0.023) and adenocarcinoma histology (7.0 mo vs. not reached, P=0.003). Conclusion: Spry2 expression was lower in tumor tissues than in normal lung parenchyma. Increased expression of Spry2 is associated with poor prognosis. There were no significant associations between epidermal growth factor receptor, anaplastic lymphoma kinase, or c-ros oncogene 1 rearrangement and Spry2 expression. Despite the absence of KRAS mutational analysis, the clinical and epidemiological features of patients suggested that KRAS mutation might be an underlying determinant factor of the functional role of Spry2 in non–small cell lung cancer.