Comprehensive analysis of the expression and prognosis for IQ motif-containing GTPase-activating proteins in hepatocellular carcinoma

Abstract

Background: IQ motif-containing GTPase-activating proteins (IQGAPs) are a group of scaffold proteins which have been identified to be involved in tumor initiation and progression in diverse types of cancer. Clinical studies and experimental evidence suggest that IQGAPs play an essential role in hepatocellular carcinoma (HCC) progression and alterations in their expression are closely related to patient prognosis. However, the different expression patterns and prognostic values of all three IQGAP isoforms in HCC have not yet been analyzed simultaneously. Methods: We analyzed the transcriptional and survival data of IQGAPs in HCC patients using Oncomine, UALCAN, Kaplan–Meier Plotter, cBioPortal, and GeneMANIA. We further examined tumor and adjacent normal tissues from 250 HCC patients using immunohistochemistry to assess the relationship between IQGAPs expression and clinicopathological features and validate the prognostic value of IQGAPs. In addition, we analyzed transcriptional changes of IQGAPs with regards to survival data in HCC patients from the TCGA-LIHC (liver hepatocellular carcinoma) cohort to validate our results. Results: We found that the expression levels of IQGAP1 and 3 were significantly elevated in HCC tissues than in normal liver tissues, whereas the expression level of IQGAP2 was decreased in the former than in the latter. The clinical data showed that positive IQGAP1 expression was associated with larger tumor size, advanced tumor-node-metastasis (TNM) stage, poor relapse-free survival (RFS), and overall survival (OS), and positive IQGAP3 expression was associated with poorer tumor differentiation, RFS, and OS. Conversely, positive IQGAP2 expression predicted less tumor numbers and microvascular invasion, as well as higher RFS and OS in these patients. Conclusions: IQGAPs may serve as new prognostic biomarkers and potential targets for precision therapy in HCC.