Abstract
Epithelial cells are held together by tight and adherent junctions, which are destroyed by the activation of epithelial-to-mesenchymal transition (EMT). The PLEKHA7-PDZD11 complex has been reported to be important for epithelial cell adhesion and connecting tissues. However, there is no research regarding the expression and role of PDZD11 in liver hepatocellular carcinoma (LIHC) progression. Here, we analyzed PDZD11 mRNA expression and its clinical results in LIHC patient RNA sequencing data based on different open databases. Furthermore, we examined differences in PDZD11 expression in LIHC tissues and cell lines using western blotting and real-time qPCR. These results are the first to report that the mRNA and protein levels of PDZD11 are significantly overexpressed in LIHC. Moreover, high expression of PDZD11 was correlated with poor overall survival in patients with LIHC. Gene regulatory network analysis suggested that PDZD11 is mainly involved in copper ion homeostasis, proteasome, and oxidative phosphorylation pathways. Interestingly, we found that PDZD11 levels were positively correlated with the abundance of immune infiltrates. In particular, higher infiltration levels of CD4+ T cells and macrophage subsets significantly affected LIHC patient prognosis. Taken together, these results demonstrate that PDZD11 could be a potential diagnostic and prognostic biomarker in LIHC.
Highlights
Liver hepatocellular carcinoma (LIHC) accounts for the most common form of primary liver cancers (Villanueva, 2019), with an increasing incidence, in East Asia (Bray et al, 2018; Siegel et al, 2019)
The results showed that the most frequent kinase targets, miRNA targets, and transcription factor targets were kinase CDK5, three miR-200 family members, FIGURE 5 | Differentially expressed genes that correlated with PDZD11 in liver hepatocellular carcinoma (LIHC) (LinkedOmics database). (A) A Pearson test was used to determine the correlations between PDZD11 and differently expressed genes in LIHC. (B,C) Heat maps are showing genes (Top 50) positively or negatively correlated with PDZD11 in LIHC
Because PDZD11 overexpression is associated with poor prognosis in LIHC patients (Figure 4), we explored whether the expression of PDZD11 was correlated with levels of immune infiltration in LIHC from the Tumor Immune Estimation Resource (TIMER) database and/or TIMER2.0 database
Summary
Liver hepatocellular carcinoma (LIHC) accounts for the most common form of primary liver cancers (Villanueva, 2019), with an increasing incidence, in East Asia (Bray et al, 2018; Siegel et al, 2019). LIHC is currently the third leading cause of cancer-related death worldwide (Jiang et al, 2019). LIHC likely occurs in patients with underlying liver diseases since infection with the hepatitis B or C virus (HBV or HCV) and long-term intoxication with alcohol or aflatoxin are the leading risk factors for developing LIHC (Jemal et al, 2017; Villanueva, 2019). Due to the high rate of recurrence and metastasis, the 5-year overall rate of survival for LIHC is only 18%, making liver cancer the second-leading cause. Operative treatment may be effective in the early stage of LIHC, the 5-year survival rate after developing to later stage is only 50–70% [European Association for the Study of the Liver (EASL), 2018]. It is important to further screen LIHC oncogenes to help identifying novel biomarkers, therapeutic targets and immune-related biomarkers, and contribute to better diagnosis and prognosis of LIHC
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