Effect of GluA1 interacting proteins GNAI2 and SRSF10 on prognosis of Hepatocellular carcinoma and establishment of diagnostic model

Abstract:

Objective To investigate the effect of AMPA glutamate receptor subunit 1（glutamate A1，GluA1） interacting proteins GNAI2 and SRSF10 on drug-related targets，prognostic indicators，and diagnostic models of hepatocellular carcinoma（HCC）.Methods GluA1 interacting proteins were obtained by proteomic methods. Transcriptome data and the corresponding clinical data of liver hepatocellular carcinoma were obtained from the Xena database（https：//xenabrowser.net/）. Genes expressed in 75% of the samples and primary tumor and para-carcinoma tissue samples were retained for subsequent analysis. The limma package standard process in R language was used to perform variation analysis on the samples. The intersection of GluA1 interacting proteins and differentially expressed genes was obtained for expression analysis，univariate COX analysis，and survival curve analysis. The PDBePISA database was used to verify the molecular docking of the candidate protein set with GluA1. The string database was used to analyze the targets of HCC-related drugs in the candidate protein set. Prognostic indicators of patients were analyzed by the multivariate COX analysis. The logistic regression model was used to construct a diagnostic model for HCC.Results Six candidate proteins，namely KIF1A，GNAI2，RPL3，ARPC1A，EIF3H，and SRSF10，were obtained with strong affinity to GluA1. GNAI2 and SRSF10 were secondary targets of Regorafenib in HCC，and the univariate and multivariate COX analyses showed that they had significant effects on patient survival（P=0.000 339，0.0404）. GNAI2 and SRSF10 were higher in level in the disease group than in the normal group（Z=3.584，2.049； hazard ratio（HR）=2.38，1.18），and are adverse prognostic factors. In the diagnostic model of HCC，the HR coefficients were 11.8455 and -0.2037，respectively，and the area under the curve of this model on the training set was 0.971，indicating excellent performances.Conclusion GluA1 interacting proteins GNAI2 and SRSF10 are secondary targets of Regorafenib in HCC，which may become prognostic indicators independent of other factors and have certain diagnostic significance.