Detection of ectopic phosphorylated PDGFRA antibodies in the serum samples of HCC patients

Hepatocellular carcinoma (HCC) is one of the most lethal cancers for humans. Early diagnosis of HCC can significantly enhance the treatment outcomes and reduce disease mortality. MAN2A1-FER is one of the most frequent oncogenic fusion genes in HCC. Our previous studies showed that MAN2A1-FER ectopically phosphorylated the extracellular domain of PDGFRA. The present study aimed to examine the diagnostic utility of antibodies specific for the ectopically phosphorylated PDGFRA generated by MAN2A1-FER in HCC patients' serum samples. In this study, 130 serum samples from HCC (65) patients and non-HCC (65) patients were analyzed. Our results showed that the antibody levels specific for the ectopically phosphorylated PDGFRA were 3.5- to 10-fold elevated in the serum samples from HCC patients in comparison with individuals without liver cancers and negative for MAN2A1-FER gene fusion. The higher titers of anti-ectopic-pPDGFRA-N-terminus in the serum samples correlated with the HCC diagnosis and outperformed the serum alpha-fetal protein for the diagnosis of HCC. The presence of these antibodies was also highly correlated with the levels of MAN2A1-FER mRNA in these serum samples. We concluded that the elevated serum levels of anti-pPDGFRA-N-terminus antibodies are highly predictive of liver cancer and can be utilized as a potential diagnostic marker for HCC.