Increased PPARD Expression May Play a Protective Role in Human Lung Adenocarcinoma and Squamous Cell Carcinoma.

Yong Zhu,Yibo Shan,Guiping Yu,Zhonghua Qin,Kamil Kural,Yedong Mi,Xuewei Jiang,Sha Liu

doi:10.1155/2022/9414524

Abstract

Peroxisome proliferator-activated receptor-δ, encoded by gene PPARD, is overexpressed in a majority of human lung cancer subtypes, but its role in the tumor progression remains poorly understood. We have analyzed the expression of PPARD in lung adenocarcinoma (LA) and squamous cell carcinoma (LSCC) datasets. The potential roles of PPARD in the pathological development of LA and LSCC were explored through literature-based pathway analysis and pathway enrichment analysis. In all LA datasets (N = 11) and in seven out of nine LSCC studies, the levels of PPARD were increased as compared to control tissues (log-fold changes were 0.37 ± 0.20 and 0.10 ± 0.37 for LA and LSCC, respectively). On average, the expression levels of PPARD in LA were higher than those in LSCC (p = 0.036). Pathway analysis showed that the overexpression of PPARD might play both positive and negative roles in the development of both LA and LSCC. Specifically, PPARD inhibits seven LSCC promoters and seven LA promoters and activates one LSCC inhibitor and another LA inhibitor. However, PPARD also activates six and one promoters of LA and LSCC, respectively, which would facilitate the development of LA/LSCC. Our results suggested a mixed role of PPARD in LA/LSCC, which may add new insights into the understanding of the PPARD-lung cancer relationship.

Highlights

Lung carcinoma (LC) is a leading cause of cancer death worldwide [1]
The latter is further subdivided into lung adenocarcinoma (LA), which comprises around 40% of all LC [1], and lung squamous cell carcinoma (LSCC) that accounts for about 30% of all lung cancer [1, 4]
Pathway Enrichment Analysis for LA/LSCC Regulators Driven by PPARD

Summary

Introduction

Lung carcinoma (LC) is a leading cause of cancer death worldwide [1]. Annually, lung cancer kills nearly 1.8 million people, more than breast, prostate, pancreatic, and colorectal cancers combined [2]. Lung cancer has been divided into two main histological types, namely, small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC) [3]. The latter is further subdivided into lung adenocarcinoma (LA), which comprises around 40% of all LC [1], and lung squamous cell carcinoma (LSCC) that accounts for about 30% of all lung cancer [1, 4]. Several previous studies suggested a strong association between the expression levels of peroxisome proliferatoractivated receptor ß/d- (PPARD-) encoding gene and human lung cancer [5–8]. A majority of the studies found that PPARD is overexpressed in lung cancer [5, 8, 9], with one recent study pointing at the association of high expression levels of this gene with a worse prognosis [10]. Even if some studies unequivocally point at PPARD as a lung cancer-promoting gene [8], others suggest that ligand-driven activation of PPARD may suppress the growth of lung cancer [6] by inhibiting inflammation [7]

Methods

Results

Conclusion