High expression of PARD3 predicts poor prognosis in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most commonly cancers with poor prognosis and drug response. Identifying accurate therapeutic targets would facilitate precision treatment and prolong survival for HCC. In this study, we analyzed liver hepatocellular carcinoma (LIHC) RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), and identified PARD3 as one of the most significantly differentially expressed genes (DEGs). Then, we investigated the relationship between PARD3 and outcomes of HCC, and assessed predictive capacity. Moreover, we performed functional enrichment and immune infiltration analysis to evaluate functional networks related to PARD3 in HCC and explore its role in tumor immunity. PARD3 expression levels in 371 HCC tissues were dramatically higher than those in 50 paired adjacent liver tissues (p < 0.001). High PARD3 expression was associated with poor clinicopathologic feathers, such as advanced pathologic stage (p = 0.002), vascular invasion (p = 0.012) and TP53 mutation (p = 0.009). Elevated PARD3 expression also correlated with lower overall survival (OS, HR = 2.08, 95% CI = 1.45–2.98, p < 0.001) and disease-specific survival (DSS, HR = 2.00, 95% CI = 1.27–3.16, p = 0.003). 242 up-regulated and 71 down-regulated genes showed significant association with PARD3 expression, which were involved in genomic instability, response to metal ions, and metabolisms. PARD3 is involved in diverse immune infiltration levels in HCC, especially negatively related to dendritic cells (DCs), cytotoxic cells, and plasmacytoid dendritic cells (pDCs). Altogether, PARD3 could be a potential prognostic biomarker and therapeutic target of HCC.

Single-cell transcriptomics and deep tissue proteomics reveal distinct tumour microenvironment present in stage-I and II cervical cancer

“…1A). After quality control, a total of 72,128 cells (42,928 stage-I and 29,200 stage-II) were used for downstream analysis (Fig. 1B).…”

“…The rst subtype, cluster 0 characterised by MS4A6A, CD163 and CD163L, had the phenotype of resident-like macrophage, thus it was referred to as C0-Res thereafter. A few marker genes of the cluster 1 were found to be associated with tumorigenesis, such as PARD3 [42], EGFR [43], and SMAD3 [44], was thus labelled as C1-TAM (Table S4). The third subtype showed the signi cant upregulation of the markers of M2-like MΦ, including SLC16A10 [45], SLC11A1 [46] and CTSL [47], and thus we named it C2-M2.…”

A comprehensive analysis of the significance of immunogenic cell death-related genes in the prognosis and immune microenvironment of patients with bladder cancer

“…DNA copy number and DNA methylation regulate HSPG2 expression in oligodendroglioma [39]. PARD3 is involved in a number of immunoinvasive levels and may be a potential prognostic biomarker and therapeutic target for hepatocellular carcinoma [40].…”

miR-559 Inhibits Proliferation, Autophagy, and Angiogenesis of Hepatocellular Carcinoma Cells by Targeting PARD3

“…Also, activation of PARD3 signaling was associated with the increased autophagy activity and colorectal cancer cell proliferation [ 15 ]. It was found that PARD3 was overexpressed in HCC and associated with poor prognosis [ 16 ]. However, its role in HCC has not been reported.…”