Abstract
BackgroundThe metastasis-associated in colon cancer 1 gene (MACC1) has been found to be associated with cancer development and progression. The aim of this study was to investigate the prognostic value of MACC1 in early-stage and AFP-normal hepatocellular carcinoma (HCC).MethodsmRNA and protein levels of MACC1 expression in one normal liver epithelial cells THLE3 and 15 HCC cell lines were examined using reverse transcription-PCR and Western blot. MACC1 expression was also comparatively studied in 6 paired HCC lesions and the adjacent non-cancerous tissue samples. Immunohistochemistry was employed to analyze MACC1 expression in 308 clinicopathologically characterized HCC cases. Statistical analyses were applied to derive association between MACC1 expression scores and clinical staging as well as patient survival.ResultsLevels of MACC1 mRNA and protein were higher in HCC cell lines and HCC lesions than in normal liver epithelial cells and the paired adjacent noncancerous tissues. Significant difference in MACC1 expression was found in patients of different TNM stages (P<0.001). Overall survival analysis showed that high MACC1 expression level correlated with lower survival rate (P = 0.001). Importantly, an inverse correlation between MACC1 level and patient survival remained significant in subjects with early-stage HCC or with normal serum AFP level.ConclusionsMACC1 protein may represent a promising biomarker for predicting the prognosis of HCC, including in early-stage and AFP-normal patients.
Highlights
Primary hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed cancer and the third most common cause of cancer mortality worldwide [1]
As the number of HCC patients who are in early stages of the disease, bear small tumor nodules (,3 cm), or display normal serum level of AFP is increasing, finding new prognosis prediction biomarker for these patients represents a major challenge in the clinic
To determine whether metastasis-associated in colon cancer 1 gene (MACC1) upregulation found in liver cancer cell lines was clinically relevant, Western blot analysis was performed with 6 paired HCC tissues and non-cancerous tissues adjacent to HCC tumors, with each pair taken from the same patient
Summary
Primary hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed cancer and the third most common cause of cancer mortality worldwide [1]. Prediction of prognosis plays an essential role in the assessment of HCC patients and optimal therapeutic options. Both tumor- (e.g., alpha fetal protein (AFP), tumor size and portal vein thrombosis) and cirrhosis-based (mainly, the Child–Pugh class) parameters are commonly employed to predict patient survival [4]. As the number of HCC patients who are in early stages of the disease, bear small tumor nodules (,3 cm), or display normal serum level of AFP is increasing, finding new prognosis prediction biomarker for these patients represents a major challenge in the clinic. The aim of this study was to investigate the prognostic value of MACC1 in early-stage and AFP-normal hepatocellular carcinoma (HCC)
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