The Expression of Caspase-3 and GRIM-19 in Non-mucinous Lung Adenocarcinoma and Their Clinicopathologic Significance

Abstract

Aim: The current study aimed to investigate apoptotic proteins such as caspase-3 and GRIM-19 protein expression in non-mucinous lung adenocarcinomas and their clinicopathologic significance. Material and Methods: This study was performed on 81 patients diagnosed with non-mucinous lung adenocarcinoma between January 1, 2010, and June 1, 2020. Immunohistochemical analysis was performed to examine the expressions of caspase-3 and GRIM-19, and the association between these proteins and clinicopathological parameters was investigated. Results: Caspase-3 nuclear positivity was more common in high-grade non-mucinous lung adenocarcinomas (p<0.001). Caspase-3 cytoplasmic expression was stronger in tumors with advanced-stage (p=0.021) and lymph node metastases (p=0.020). GRIM-19 expression was low in tumors with high-grade non-mucinous lung adenocarcinomas (p=0.002), and tumors with lymphovascular invasion (p=0.021). The median follow-up time was 31.7 (range, 1-145 months. The overall 5-year survival rate of patients with low and high GRIM-19 expression tumors was 48% and 92%, respectively. GRIM-19 expression significantly affected the 5-year overall survival rate (p=0.008), but not the 5-year disease-free survival rate (p=0.368). Conclusion: We revealed a significant association between caspase-3 and GRIM-19 expressions and poor clinicopathologic features and prognosis. For the first time in the literature, we revealed an association between low GRIM-19 expression and worse clinical outcomes in patients with non-mucinous lung adenocarcinoma. Caspase-3 and GRIM-19 may become potential therapeutic targets and novel potential predictive biomarkers for non-mucinous lung adenocarcinoma patients.

Keywords

• apoptosis
• caspase-3
• grim-19
• lung cancer
• apoptosis
• caspase-3
• grim-19
• akciğer kanseri