Arp2/3 Complex Subunits as Prognostic Biomarkers and Their Correlations With Immune Infiltration in Hepatocellular Carcinoma
Abstract Introduction: Actin‐related protein 2/3 complex (Arp2/3) is a major actin nucleator containing seven subunits in humans, which has been widely reported that Arp2/3 plays an important role in promoting migration and invasion of various kinds of cancers. Nevertheless, the expression patterns and prognostic values of Arp2/3 subunits and the correlation between ARP2/3 subunits with immune infiltration in hepatocellular carcinoma remains unclear.Methods: TCGA-FPKM dataset, Oncomine, CCLE and UCSC Xena database was used to obtained mRNA expression and clinical information of Arp2/3 subunits in HCC. The Arp2/3 subunits differential expression in HCC tissues and cell lines was analyzed by utilizing the Perl 5.30.0 and R 4.0.4 software. The protein expression data of Arp2/3 subunits was obtained from The Human Protein Atlas (HPA). The prognostic value of each individual Arp2/3 subunits was identified by R 4.0.4 software. The association between the mRNA expressions of Arp2/3 members in HCC tissues with their clinicopathologic parameters was analyzed by UALCAN. The relevance between tumor immunocyte infiltration and the Arp2/3 complex members were determined by the TIMER 2.0 platform and GEPIA database. A gene set enrichment analysis (GSEA) was performed to explore the potential mechanism of Arp2/3 complex members in the carcinogenesis of HCC.Results:The results revealed that expression of Arp2/3 family members(ACTR2,ACTR3,ARPC1A, APRC1B,ARPC2,ARPC3,ARPC4, ARPC5, ARPC5L) were up-regulated in hepatocellular carcinoma (HCC). Moreover, higher protein expressions of of ACTR3, ARPC1A, ARPC1B, ARPC2 were found in HCC tissues compared with normal liver tissues. The higher expression of of Arp2/3 family members were significantly correlated with poor survival and cancer stages in HCC patients. Multivariate analysis also demonstrated that ACTR3, ARPC2 and ARPC5 were independent prognostic biomarkers of survival in HCC patients. Meanwhile, ACTR3, ARPC2 and ARPC5 in HCC has positive significant correlations with the infiltration of immune cells. The GSEA results indicated that Arp2/3 members significantly involve in multiple cancer-related pathways by which promoted development of HCC. Conclusions:Various analysis indicated that certain Arp2/3 complex subunits were noticeably upregulated and predicted worse survival in HCC, which may be applied as promising molecular targets for diagnosis and therapy of HCC in the future.