Lung Adenocarcinoma With Bone Metastases: Clinicogenomic Profiling and Insights Into Prognostic Factors

Abstract

Introduction: Lung adenocarcinoma is the leading cause of cancer-related mortality worldwide. Understanding the clinicopathological profiles and genomic drivers of its metastatic patterns is a crucial step for risk stratification. Herein, we investigated the clinicogenomic features of bone metastases in lung adenocarcinoma and their prognostic value. Methods: A retrospective cohort study with a total of 4064 patients with various metastatic patterns of lung adenocarcinoma were included, obtaining relevant clinical data and genomic profiles. Patients were categorized based on the presence or absence of bone metastases. A comparative analysis of both groups in terms of demographics, disease status, somatic mutations, and microsatellite instability was carried out. Significantly different variables were tested for their association with bone metastases. Cox regression analyses were utilized to identify independent survival prognostic variables in the bone metastases sub-cohort. Results: Gender, concomitant metastases (to adrenal gland, nervous system, lymph nodes, liver, lung, mediastinum, pleura, and skin), and aberrations in TP53, EGFR, KEAP1, and MYC were associated with bone metastases in lung adenocarcinoma. Survival analyses within the bone metastases sub-cohort have illustrated the following variables to possess poor prognostic signature including age > 75, female gender, White ethnicity, distant metastases (adrenal gland, central nervous system, intra-abdominal, and liver), EGFR (wild type), KEAP1 (mutant), MYC (mutant), KRAS (mutant), and SMARCA4 (mutant). Conclusion: Key clinical and genomic factors associated with lung adenocarcinoma bone metastases have been highlighted, providing exploratory insights into high-risk individuals. Future studies should be directed to validate these prognostic variables in larger, more diverse cohorts to enhance generalizability.