Affiliation:
1. Department of Pathology, Baskent University Faculty of Medicine
2. Department of Pathology, Baskent University Faculty of Medicine of Pathology
3. Department of Thoracic Surgery, Baskent University Faculty of Medicine
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.
Reference33 articles.
1. WHO Classification of Tumours Editorial Board. Thoracic Tumours. 5th ed. Lyon, France: International Agency for Research on Cancer; 2021.
2. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33.
3. Haura EB, Cress WD, Chellappan S, Zheng Z, Bepler G. Antiapoptotic signaling pathways in non-small-cell lung cancer: biology and therapeutic strategies. Clin Lung Cancer. 2004;6(2):113-22.
4. Eskandari E, Eaves CJ. Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis. J Cell Biol. 2022;221(6):e202201159.
5. Boice A, Bouchier-Hayes L. Targeting apoptotic caspases in cancer. Biochim Biophys Acta Mol Cell Res. 2020;1867(6):118688.