Prognostic marker VPS72 could promote the malignant progression of prostate cancer

Abstract

Background: This paper attempted to clarify the role and mechanism of vacuolar protein sorting-associated protein 72 homolog (VPS72) in the progression of prostate cancer (PCa).

Methods: Clinical information and gene expression profiles of patients with prostate cancer were obtained from The Cancer Genome Atlas (TCGA). VPS72 expression in PCa and the potential mechanism by which VPS72 affects PCa progression was investigated. Next, we performed COX regression analysis to identify the independent prognostic factors of PCa, and constructed a nomogram. The sensitivity of chemotherapeutic medications was anticipated using "pRRophetic". Subsequently, in vitro assays to validate the effect of VPS72 on PCa cell proliferation, migration and susceptibility to anti-androgen therapy.

Results: The expression of VPS72 was considerably higher in PCa tissues compared to normal tissues. Significant correlations were found between high VPS72 expression and a poor prognosis and adverse clinicopathological factors. The nomogram model constructed based on VPS72 expression has good predictive performance. According to GSEA, VPS72-related genes were enriched in the NF-kB pathways, cytokine-cytokine receptor interaction and chemokine signaling pathway in PCa. Although PCa with low VPS72 expression was more adaptable to chemotherapeutic medications, our in vitro experiment showed that VPS72 knockdown significantly decreased the PCa cell migration, proliferation, and resistance to anti-androgen therapy.

Conclusions: In summary our findings suggests that VPS72 could play a crucial role in the malignant progression of PCa, and its expression level can be employed as a possible biomarker of PCa prognosis.

Keywords: Clinical prognosis; Nomogram; Prostate cancer; VPS72.

Fig. 1

The VPS72 expression pattern and its correlation with the clinical features of PCa patients. (A) Expression of VPS72 in pan-cancer samples and normal tissues. (B) Expression of VPS72 in PCa and normal tissues. (C) Expression of VPS72 in PCa and a matching, nearby normal sample. Relationship between VPS72 expression level and the (D) Gleason Score; (E) T stage; (F) N stage; (G) M stage. (ns p ≥ 0.05, *P < 0.05; **P < 0.01; ***P < 0.001)

Fig. 2

Prognostic value of VPS72 expression level in PCa that is independent. (A) The findings of the univariate and multivariate Cox regression analyses are displayed in the forest plot. (B) Progression-free interval (PFI) for VPS72 in all patients was analyzed using the Kaplan-Meier curve; (C–E) age, residual tumor, and T stage-specific Kapla-Meier survival analyses were performed

Fig. 3

VPS72 expression has diagnostic relevance for PCa patients. (A) The VPS72 ROC curve in PCa and normal prostate tissue. (B) The VPS72 time-dependent ROC curve in both PCa and normal prostate tissue. (C) Calibration plots showing the degree of agreement between the real survival rate and the rate predicted by the nomogram. (D) Nomogram for estimating the likelihood that PCa patients with 1, 3, and 5-year PFI

Fig. 4

Biological Function of VPS72 expression levels in PCa. (A) GSEA pathway enrichment analysis between patients with high and low VPS72 expression. (B) Correlations of VPS72 expression with the sensitivity of chemotherapeutic medications in PCa

Fig. 5

Relationship between VPS72 and viability of LNCaP cells. (A) qRT-PCR assay shows the transcriptional levels of the VPS72 gene with GAPDH used as the loading control in LNCaP cells. (B) Effect of sh-VPS72 on the proliferation of LNCaP cells was detected by CCK-8 assays. (C) Changs in cellular invasiveness of LNCaP cells were investigated via 3D culture. (D) Migration of LNCaP cells was detected via wound healing assay. (E) Apoptosis of LNCaP cells induced by Bicalutamide (10µM) were measured by flow cytometry analyses. Data are presented as the mean ± SD for three independent experiments (*P < 0.05)