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

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...

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Main Authors: Wanwan He, Meilian Wei, Yan Huang, Junsen Qin, Meng Liu, Na Liu, Yanli He, Chuanbing Chen, Yali Huang, Heng Yin, Ren Zhang
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/14/5/566
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author Wanwan He
Meilian Wei
Yan Huang
Junsen Qin
Meng Liu
Na Liu
Yanli He
Chuanbing Chen
Yali Huang
Heng Yin
Ren Zhang
author_facet Wanwan He
Meilian Wei
Yan Huang
Junsen Qin
Meng Liu
Na Liu
Yanli He
Chuanbing Chen
Yali Huang
Heng Yin
Ren Zhang
author_sort Wanwan He
collection DOAJ
description 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 <i>p</i>-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.
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spelling doaj-art-bbbc91c8f1d14ac28c0c00dad28382272025-08-20T01:56:17ZengMDPI AGBiology2079-77372025-05-0114556610.3390/biology14050566Integrated Bioinformatics Analysis and Cellular Experimental Validation Identify Lipoprotein Lipase Gene as a Novel Biomarker for Tumorigenesis and Prognosis in Lung AdenocarcinomaWanwan He0Meilian Wei1Yan Huang2Junsen Qin3Meng Liu4Na Liu5Yanli He6Chuanbing Chen7Yali Huang8Heng Yin9Ren Zhang10Research Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaResearch Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaResearch Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaResearch Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaResearch Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaResearch Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaResearch Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaResearch Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaInstitute of Infectious Diseases, Guangzhou Medical University, Guangzhou 510182, ChinaResearch Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaLung 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 <i>p</i>-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.https://www.mdpi.com/2079-7737/14/5/566lipoprotein lipaselung adenocarcinomaSMRtargeted therapeuticIncuCyte
spellingShingle Wanwan He
Meilian Wei
Yan Huang
Junsen Qin
Meng Liu
Na Liu
Yanli He
Chuanbing Chen
Yali Huang
Heng Yin
Ren Zhang
Integrated Bioinformatics Analysis and Cellular Experimental Validation Identify Lipoprotein Lipase Gene as a Novel Biomarker for Tumorigenesis and Prognosis in Lung Adenocarcinoma
Biology
lipoprotein lipase
lung adenocarcinoma
SMR
targeted therapeutic
IncuCyte
title Integrated Bioinformatics Analysis and Cellular Experimental Validation Identify Lipoprotein Lipase Gene as a Novel Biomarker for Tumorigenesis and Prognosis in Lung Adenocarcinoma
title_full Integrated Bioinformatics Analysis and Cellular Experimental Validation Identify Lipoprotein Lipase Gene as a Novel Biomarker for Tumorigenesis and Prognosis in Lung Adenocarcinoma
title_fullStr Integrated Bioinformatics Analysis and Cellular Experimental Validation Identify Lipoprotein Lipase Gene as a Novel Biomarker for Tumorigenesis and Prognosis in Lung Adenocarcinoma
title_full_unstemmed Integrated Bioinformatics Analysis and Cellular Experimental Validation Identify Lipoprotein Lipase Gene as a Novel Biomarker for Tumorigenesis and Prognosis in Lung Adenocarcinoma
title_short Integrated Bioinformatics Analysis and Cellular Experimental Validation Identify Lipoprotein Lipase Gene as a Novel Biomarker for Tumorigenesis and Prognosis in Lung Adenocarcinoma
title_sort integrated bioinformatics analysis and cellular experimental validation identify lipoprotein lipase gene as a novel biomarker for tumorigenesis and prognosis in lung adenocarcinoma
topic lipoprotein lipase
lung adenocarcinoma
SMR
targeted therapeutic
IncuCyte
url https://www.mdpi.com/2079-7737/14/5/566
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