Abstract
The calcium-binding protein S100P is expressed in a variety of human cancer cells and is important in cancer cell growth and invasion. Using differential display, we found S100P is overexpressed in human hepatocellular carcinoma (HCC). We examined the expression of 305 unifocal, primary HCC tumors using immunohistochemistry. The S100P protein was expressed in 173 of the 305 (56.7%) HCC tumors. The expression of S100P correlated with female sex (P = 0.0162), high serum α-fetoprotein level (P = 0.0001), high tumor grade (P = 0.0029), high tumor stage (P = 0.0319), the presence of the p53 mutation (P = 0.0032), and the absence of the β-catenin mutation (P = 0.0489). Patients with HCC tumors that expressed S100P were more likely to have early tumor recurrence (ETR) (P = 0.0189) and lower 5-year survival (P = 0.0023). The multivariate analysis confirmed that S100P expression was an independent prognostic factor in HCC. The combinatorial analysis showed an additive unfavorable prognostic interaction between S100P expression and the p53 mutation. In contrast, the β-catenin mutation was associated with better prognosis in both S100P-positive and -negative HCCs. Furthermore, S100P expression was a predictor of survival in HCC patients with high tumor stage or ETR (P = 0.0026 and P = 0.0002, respectively). Our study indicates the expression of the S100P protein is a novel independent predictor for poor prognosis in HCC, and it is also an unfavorable prognostic predictor in HCC patients with high tumor stage or ETR.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, in Taiwan, southern China, Southeast Asia, and sub-Saharan Africa, and the incidence of HCC is increasing in Western countries [1]
In about 10% of all cases, the S100P protein was detected in a small subset of hepatocytes that usually comprised less than 1% of the total hepatocytes
S100P was reported to be expressed in various types of human cancer cells [13,15,19,24,25,26,27,28,29,30,31,32], including human HCC [33], the clinical and pathological significances of S100P
Summary
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, in Taiwan, southern China, Southeast Asia, and sub-Saharan Africa, and the incidence of HCC is increasing in Western countries [1]. Surgical resection and various methods of tumor ablation can be curative or prolong survival, the outcome for patients with HCC remains grave. This is true in advanced-stage HCC because the tumor has often spread throughout the liver via the intrahepatic portal venous system, and a considerable number of HCC patients develop early intrahepatic and/or extrahepatic recurrence postoperatively [3]. The molecular factors related to tumor progression and ETR in HCC remain unclear. The identification of molecular markers that correlate with tumor progression, ETR, and poor prognosis would aid efforts to establish better treatment plans for HCC patients
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