PVT1 and MALAT1 Upregulation Correlates with Immune Checkpoints and Outcomes in African American Lung Cancer

BackgroundAfrican Americans have the highest incidence and mortality rates of lung cancer among racial groups. Although therapies targeting the programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathways have revolutionized treatment, their efficacy remains inconsistent, and adverse effects present significant challenges. Understanding the association between molecular changes and immune factors in the tumor immune microenvironment is critical for improving treatment outcomes and addressing racial disparities. Our previous research demonstrated that the upregulation of the long non-coding RNAs PVT1 and MALAT1 is associated with lung cancer in African Americans. This study investigates the relationship between dysregulated long non-coding RNAs, immune markers, and survival outcomes in a large cohort of lung cancer patients. MethodsTumor tissues were collected from 256 lung cancer patients, including 125 African Americans and 131 White Americans, who underwent lobectomy or pneumonectomy. PVT1 and MALAT1 expression levels were quantified using droplet digital polymerase chain reaction. Immune markers, including programmed death-ligand 1, programmed cell death protein 1, CD8+ T cell infiltration, CD69, interferon-gamma, and tumor necrosis factor-alpha, were analyzed through immunohistochemistry. Statistical analyses were performed to evaluate relationships between molecular changes, immune markers, and survival outcomes in this large cohort. ResultsElevated PVT1 expression was associated with increased levels of programmed death-ligand 1 and programmed cell death protein 1, reduced CD69 expression, lower levels of interferon-gamma and tumor necrosis factor-alpha, advanced disease, and poorer survival outcomes in African American patients. MALAT1 upregulation was correlated with increased levels of programmed death-ligand 1 and programmed cell death protein 1, reduced immune effector activity, and worse survival outcomes in both African American and White American patients. Combined analysis of PVT1 and MALAT1 expression improved prognostic accuracy in African American lung cancer patients compared to individual assessments. ConclusionsThe dysregulation of PVT1 and MALAT1 is associated with immune evasion and advanced lung cancer among African Americans. PVT1 and MALAT1 may serve as prognostic biomarkers and therapeutic targets to improve the efficacy of immunotherapy for African American lung cancer patients. Leveraging these insights has the potential to reduce racial disparities in lung cancer outcomes and advance personalized treatment strategies. Key PointsO_LISignificant findings of the study O_LIDysregulated PVT1 and MALAT1 are associated with immune evasion, advanced lung cancer, and poor survival in African Americans. C_LIO_LICombined analysis of PVT1 and MALAT1 enhances prognostic accuracy compared to individual assessments. C_LI C_LIO_LIWhat this study adds O_LIHighlights PVT1 and MALAT1 as prognostic biomarkers and therapeutic targets in African American lung cancer patients. C_LIO_LIProvides insights to improve immunotherapy efficacy and address racial disparities in lung cancer outcomes. C_LI C_LI