Abstract
Previous studies showed that PPAR-gamma (PPARG) ligands might serve as potential therapeutic agents for nonsmall cell lung cancer (NSCLC). However, a few studies reported the specific relationship between PPARG and lung squamous cell carcinoma (LSCC). Here, we made an effort to explore the relationship between PPARG and LSCC. First, we used mega-analysis and partial mega-analysis to analyze the effects of PPARG on LSCC by using 12 independent LSCC expression datasets (285 healthy controls and 375 LSCC cases). Then, literature-based molecular pathways between PPARG and LSCC were established. After that, a gene set enrichment analysis (GSEA) was conducted to study the functionalities of PPARG and PPARG-driven triggers within the molecular pathways. Finally, another mega-analysis was constructed to test the expression changes of PPARG and its driven targets. The partial mega-analysis showed a significant downregulated expression of PPARG in LSCC (LFC = −1.08, p value = 0.00073). Twelve diagnostic markers and four prognostic markers were identified within multiple PPARG-LSCC regulatory pathways. Our results suggested that the activation of PPARG expression may inhibit the development and progression of LSCC through the regulation of LSCC upstream regulators and downstream marker genes, which were involved in tumor cell proliferation and protein polyubiquitination/ubiquitination.
Highlights
PPARG is a ligand-activated transcription factor belonging to the family of peroxisome proliferator-activated receptors (PPARs) [1], which is widely expressed in many cells and tissues in the human body [2]
A number of animal models [4], cell lines [5, 6], and clinical trials [NCT00923949, NCT01199068, NCT01199055] demonstrated that activation of PPARgamma impedes lung tumor progression and suggest that PPARG ligands may serve as potential therapeutic agents for nonsmall cell lung cancer (NSCLC), with the emphasis on lung adenocarcinoma [7, 8]
There were 4,643 results shown in the gene expression omnibus (GEO) datasets identified by the keywords “lung squamous cell carcinoma”
Summary
PPARG is a ligand-activated transcription factor belonging to the family of peroxisome proliferator-activated receptors (PPARs) [1], which is widely expressed in many cells and tissues in the human body [2]. A number of animal models [4], cell lines [5, 6], and clinical trials [NCT00923949, NCT01199068, NCT01199055] demonstrated that activation of PPARgamma impedes lung tumor progression and suggest that PPARG ligands may serve as potential therapeutic agents for nonsmall cell lung cancer (NSCLC), with the emphasis on lung adenocarcinoma [7, 8]. Ni et al.’s study showed that the activation of PPARG could inhibit the proliferation of EGFR-TKI-resistant lung adenocarcinoma cells and lead to a better survival rate [8]. To our knowledge, no study has systematically studied the role of PPARG in the pathology of LSCC
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