PI3K and PINK1 Immunoexpression as Predictors of Survival in Patients with Brain Resection of Lung Adenocarcinoma Metastases

• DOI: 10.20944/preprints202502.2219.v1
• Publication Date: 2025-03-03T03:06:51Z
• Authors: Miriam Rubiera-Va...; Mª Daniela Corte-...; Andrea Navarro-Lopez; Noelia Blanco-Agudin; Santiago Fernande...; Kelvin M. Piña-Ba...; Jorge Santos-Juanes; Jesus Merayo-Lloves; Luis M. Quiros; Adela A. Fernande...; Ivan Fernandez-Vega

Phosphoinositide 3-kinase (PI3K) and PTEN-induced kinase 1 (PINK1) are key regulators of metabolism and mitochondrial quality control. This study assessed their immunoexpression in 22 patients with lung adenocarcinoma and resected brain metastases treated with curative intent (2007–2017) and evaluated their prognostic significance. Tissue microarrays of primary tumors and matched metastases were analyzed using the H-score method. PI3K expression was significantly higher in primary tumors than in metastases (96.8 ± 57.9 vs. 43.5 ± 62.3; p = 0.003) and in stage IV adenocarcinomas (113.3 ± 56.3 vs. 61.4 ± 47.1; p = 0.043). PINK1 expression showed no significant variation across disease stages. Univariate analysis identified older age (>55 years), PI3K overexpression (HR = 7.791, 95% CI 1.718–36.432; >50 points), and PINK1 overexpression (>100 points) in primary tumors as predictors of poor overall survival (HR = 2.236, 95% CI 1.109–4.508; p = 0.025). Multivariate analysis confirmed PINK1 overexpression in primary tumors as an independent prognostic factor (HR = 4.328, 95% CI 1.264–14.814; p = 0.020). These findings suggest that PI3K and PINK1 may serve as prognostic biomarkers in lung adenocarcinoma with brain metastases, highlighting the need for research on their role in tumor progression and therapeutic response.