LKB1 Expression and Clinical Outcomes in Non-Small Cell Lung Cancer: A Retrospective Cohort Study

The goal of this observational study is to investigate the clinical and biological significance of LKB1 (STK11) alterations in patients with non-small cell lung cancer (NSCLC) and to determine whether LKB1 mutation status, together with co-occurring genomic alterations, can predict therapeutic response and survival outcomes across different treatment strategies. The main question this study aims to answer is whether LKB1-driven molecular subgroups can define distinct clinical behaviors, immune phenotypes, and treatment vulnerabilities in NSCLC patients. Participants included in this study are adult patients diagnosed with NSCLC who have available tumor tissue samples, genomic sequencing data, PD-L1 immunohistochemical evaluation, and clinical follow-up information. Approximately 300 patients with NSCLC will be retrospectively enrolled. Clinical characteristics, including age, sex, smoking history, pathological subtype, TNM stage, treatment history, and survival outcomes, will be collected from medical records. Tumor tissue samples will be analyzed using targeted next-generation sequencing to identify genomic alterations involving LKB1 (STK11), KRAS, KEAP1, TP53, and other cancer-related genes. Immunohistochemistry will be performed to evaluate LKB1 protein expression and PD-L1 expression levels. Genomic profiles will be integrated with clinical characteristics and treatment information, including chemotherapy, targeted therapy, immune checkpoint inhibitor therapy, and combination treatment regimens. The study will classify patients according to biologically relevant genomic backgrounds, with LKB1 mutation as the primary molecular factor and KRAS, KEAP1, and TP53 alterations considered as important co-molecular modifiers. Different genomic subgroups will be compared to determine their associations with PD-L1 expression patterns, treatment responses, and long-term clinical outcomes. The study will evaluate whether LKB1 alteration contributes to therapeutic heterogeneity by influencing immune checkpoint inhibitor efficacy and modifying the prognostic impact of PD-L1 expression. In addition, this study will explore whether specific LKB1-associated genomic subtypes represent distinct patient populations with different responses to immunotherapy, chemotherapy, or targeted treatment approaches. Participants will not receive any experimental intervention as part of this study. All clinical treatments will have been administered according to routine medical practice. The study will analyze previously collected clinical and molecular data, together with long-term follow-up information, to establish an LKB1-centered genomic classification framework for personalized treatment stratification in NSCLC. The primary outcomes of this study are overall survival (OS) and progression-free survival (PFS). Secondary outcomes include objective response rate (ORR), disease control rate (DCR), treatment-specific clinical benefit, and the relationship between genomic alterations, PD-L1 expression, and therapeutic outcomes. This study aims to improve the understanding of how LKB1 loss influences tumor immune biology and treatment response in NSCLC and may provide a clinically applicable strategy for identifying patients who are more likely to benefit from specific therapeutic approaches.