A80-2-04 KEAP1 Loss as a Prognostic Biomarker in Lung Adenocarcinoma With Adrenal Gland Metastases

Background The adrenal glands represent a common site of neoplastic spread in various malignancies especially lung adenocarcinoma. Their presence typically signifies advanced disease and is associated with poorer outcomes. With ongoing advancements in molecular medicine, the discovery of biomarkers is an essential tool for prognosticating. Herein, we investigate the role of KEAP1, a frequently mutated tumor suppressor gene, in lung adenocarcinoma with adrenal gland metastases. Methods The MSK MetTropism lung adenocarcinoma cohort (n = 4,064) was accessed through cBioPortal to obtain a sub cohort with adrenal gland metastases (n = 514). The cohort’s clinicopathological variables in addition to KEAP1 gene status, were retrieved and analyzed. Survival analyses pipeline began with a Kaplan-Meier estimator comparison between altered (n = 113) and non-altered (n = 401) groups using the log-rank test. The prognostic value of KEAP1 loss, eliminating other confounding variables were assessed using univariate and multivariate Cox regression analyses. A P-value of less than .05 was deemed statistically significant. Results Within the lung adenocarcinoma with adrenal gland metastases cohort, patients with KEAP1 alterations demonstrated a median overall survival of 8.51 months (95% confidence interval (CI): 4.07-12.02) which was significantly (P < .01) shorter compared to the KEAP1 non-altered group with a median overall survival of 17.87 months (95% CI: 15.87-21.06). KEAP1 loss was identified as an independent poor prognostic signature (hazard ration (HR): 1.552, 95% CI 1.208-1.994, P = .001). Other poor prognostic factors were metastases to the peripheral nervous system, female genitalia, ovary, liver, intra-abdominal region, bone, and biliary track. Demographics and other metastatic sites status did not show significant survival associations. Conclusion These findings revealed the prognostic significance of KEAP1 loss and its potential role in guiding risk stratification in this patient population. Further studies with expanded cohorts are warranted to validate the generated results and to investigate the molecular mechanisms imploded in the poor prognostic signature. This abstract is funded by: None