Aberrant expression and prognostic value of RacGAP1 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, which is characterized by rapid progressive development, high degree of malignancy, high post-surgical recurrence, extremely poor prognosis and high mortality, since most HCC patients are identified at a late stage upon diagnosis. Identification of novel biomarkers for early diagnosis and predicting prognosis of HCC is therefore of urgent need, which may potentially improve the prognosis and mortality of HCC cases. Rac GTPase-activating protein 1 (RacGAP1) has been shown to correlate with the biological behaviors and poor prognosis of multiple cancers; however, the role of RacGAP1 in the development, progression and prognosis of HCC remains unknown to date. The major purpose of this study was to examine the associations of RacGAP1 with the clinicopathological characteristics and prognosis of HCC. The RacGAP1 protein was determined in 93 HCC specimens, 39 liver biopsy specimens of hepatic cirrhosis patients, 30 liver biopsy specimens of hepatitis patients and 18 normal liver specimens using immunohistochemistry, and the associations of RacGAP1 protein expression with the clinicopathological features and survival of HCC patients were evaluated. Immunohistochemical staining revealed negative RacGAP1 expression in normal liver specimens, and liver biopsy specimens of hepatitis and hepatic cirrhosis patients, while 44.1% (41/93) of HCC specimens were positive for RacGAP1 (P < 0.05). In the HCC specimens, RacGAP1 was predominantly expressed in the cytoplasm, and partially co-localized in the nucleus and cytoplasm. The RacGAP1 expression was found to correlate with the tumor size, pathological grading, TNM stage, vascular tumor thrombus and lymph node metastasis of HCC (all P values < 0.05), but not with patients' gender or age (both P values > 0.05). Univariate analysis showed a significantly lower survival rate in HCC patients with positive RacGAP1 expression, vascular invasion and advanced TNM stage, while multivariate analysis revealed that high RacGAP1 expression was an independent prognostic factor in HCC patients. The results of this study demonstrate that aberrant expression and abnormal localization of RacGAP1 in the cytoplasm and nucleus may correlate with the development and progression of HCC, and RacGAP1 may have a promising value to serve as a biomarker for malignant biological behaviors and poor prognosis of HCC.