Integrated Bioinformatics Analysis and Cellular Experimental Validation Identify Lipoprotein Lipase Gene as a Novel Biomarker for Tumorigenesis and Prognosis in Lung Adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is one of the leading causes of death worldwide, and thus, more biomarker and therapeutic targets need to be explored. Herein, we aimed to explore new biomarkers of LUAD by integrating bioinformatics analysis with cell experiments. We firstly identified 266 druggable genes that were significantly differentially expressed between LUAD tissues and adjacent normal lung tissues. Among these genes, SMR analysis with p-value correction suggested that declining lipoprotein lipase (LPL) levels may be causally associated with an elevated risk of LUAD, which was corroborated by co-localization analysis. Analyses of clinical data showed that LPL in lung cancer tissues has considerable diagnostic value for LUAD, and elevated LPL levels were positively associated with improved patient survival outcomes. Cell experiments with an LPL activator proved these findings; the activator inhibited the proliferation and migration of lung cancer cells. Next, we found that LPL promoted the infiltration of immune cells such as DCs, IDCs, and macrophages in LUAD by mononuclear sequencing analysis and TIMER2.0. Meanwhile, patients with low levels of LPL expression demonstrated superior immunotherapeutic responses to anti-PD-1 therapy. We conclude that LPL acts as a diagnostic and prognostic marker for LUAD.

Keywords

• lipoprotein lipase
• lung adenocarcinoma
• SMR
• targeted therapeutic
• IncuCyte