PLEK2 Gene Upregulation Might Independently Predict Shorter Progression-Free Survival in Lung Adenocarcinoma

Abstract

Objective: This study aimed to explore PLEK2 expression profile, its prognostic value, and the potential genomic alterations associated with its dysregulation in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Materials and methods: Data from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), and Kaplan-Meier plotter were used in combination for bioinformatic analysis. Results: PLEK2 mRNA was significantly upregulated in both LUAD and LUSC compared with their respective normal controls. PLEK2 upregulation showed independent prognostic value in progression-free survival (PFS) (HR: 1.169, 95%CI: 1.033 -1.322, p = 0.014). PLEK2 mRNA expression was positively correlated with invasion, cell cycle, DNA damage, and DNA repair of LUAD cells at the single-cell level. Genomic analysis showed that gene-level amplification might not directly lead to increased PLEK2 expression. Methylation profile analysis found 4 CpG sites (cg12199376, cg14437634, cg17641252, and cg06724236) had at least a weakly negative correlation with PLEK2 expression, among which cg12199376, cg14437634 and cg17641252 locate around the first exon of the gene. Conclusions: Increased PLEK2 expression might be a specific prognostic biomarker of poor PFS in LUAD patients. Its expression had significant positive correlations with invasion, cell cycle, DNA damage, and DNA repair of LUAD cells at the single-cell level. Promoter hypomethylation might be a potential mechanism leading to its upregulation.

TGF-β-induced PLEK2 promotes metastasis and chemoresistance in oesophageal squamous cell carcinoma by regulating LCN2

“…Shen et al found that PLEK2 promoted the processes of invasion and metastasis in GBC through the EGFR/CCL2 pathway [ 11 ]. The upregulation of PLEK2 is linked to the PFS of NSCLC [ 19 ], which is related to PLEK2-regulated metastasis and vascular invasion in NSCLC [ 20 ]. Previous studies revealed the role of PLEK2 as an oncogene in malignant cancer, and our results are consistent with those of previous studies.…”

Pleckstrin 2 is a potential drug target for colorectal carcinoma with activation of APC/β‑catenin

“…PLEK2 is a paralog of pleckstrin that can bind to polyphosphoinositides and regulate actin rearrangement ( 16 , 32 , 33 ). Dysregulation of PLEK2 is involved in the development of different cancer types ( 17 , 34 ). For instance, transcriptome analysis has demonstrated that PLEK2 is highly expressed in the whole blood cells from patients with melanoma ( 35 ).…”

“…PLEK2 expression is upregulated in patients with GBC, whereas overexpression of PLEK2 promotes GBC carcinogenesis by potentiating PLEK2/EGFR signaling ( 17 ). In addition, PLEK2 is highly expressed in lung adenocarcinoma samples and associated with poor prognosis of the patients ( 34 ). Upregulation of PLEK2 also serves a tumor-promoting role in NSCLC via regulation of the ubiquitination-dependent stabilization of SH2 domain containing inositol 5-phosphatase 2 ( 22 ).…”

Emerging Roles of Pleckstrin-2 Beyond Cell Spreading

“…Furthermore, it has also been indicated to be associated with poor prognosis in other tumors. PLEK2 is identified as an prognosis factor for prostate cancer, lung adenocarcinoma and head and neck squamous cell carcinoma in independent bioinformatics analysis with gene signature-based risk assessment models ( Yin et al, 2016 ; Jiang et al, 2020 ; Wang et al, 2020 , 2021b ; Zhang et al, 2020 ). Its expression in pancreatic cancer is positively correlated with the expression of insulin-like growth factor 2 mRNA binding protein IMP2 that is oncogenic protein known to be overexpressed in different types of cancers ( Dahlem et al, 2019 ).…”