Relationship between survivin expression and recurrence, and prognosis in hepatocellular carcinoma

Abstract

AIM:To study the expression of the inhibitor of apoptosis protein survivin in hepatocellular carcinoma (HCC), and its correlation with clinicopathological factors, cell proliferation, recurrence and prognosis after hepatectomy. METHODS:Immunohistochemical staining of survivin and Ki-67 was performed by the standard streptavidinperoxidase technique on paraffin sections of 55 cases of HCC. RESULTS:The positive rate of survivin in HCC was 52.7% (29/55). Significant correlation was found between survivin expression with portal vein thrombi and intrahepatic matastasistic nodes (P < 0.05). The recurrent rate in survivin-positive HCC was significantly h i g h e r t h a n t h a t in sur vivin-ne gat ive H CC af t e r hepatectomy, the 1-and 3-year survival rate in patients with survivin-positive tumors was significantly lower than that in patients with survivin-negative tumors (58.62 and 10.34% vs 76.92 and 30.77%, P < 0.05, log-rank test).

Increased Survivin Expression Confers Chemoresistance to Tumor-Associated Endothelial Cells

“…14,34 -38 Elevated survivin levels correlate with poor patient prognosis and likelihood of recurrence in many cancers, such as hepatocellular, 39 non-small cell lung, 40 and breast 41 carcinomas. Survivin has bi-functional roles; it drives cell division and inhibits apoptosis, as reported in renal cancer carcinoma 42 and lung cancer cells.…”

Prostaglandin E2 upregulates survivin expression via the EP1 receptor in hepatocellular carcinoma cells

“…Pathological evidence has shown a significant correlation between survivin expression and tumor stage, prognosis, and recurrence (Barnes et al 2006;Atikcan et al 2006;Ye et al 2007;Lee et al 2005). Downregulation of survivin expression by drugs or RNA interference sensitizes tumor cells to chemotherapy and induces cell apoptosis (Nakao et al 2006;Yonesaka et al 2006).…”

“…Because survivin is known to promote cell proliferation in hepatocellular carcinomas (Fields et al 2004;Ye et al 2007;Ito et al 2000), we tested the hypothesis that the PGE 2 signaling pathway stimulates cell proliferation by regulating survivin expression in liver cancer. This study demonstrates that PGE 2 greatly induces survivin expression by activating the EP1/EGFR/PI3K pathway in hepatocellular carcinoma cells.…”

The Molecular Alterations Regarding Apoptosis in Hepatocellular Carcinoma Cells at a Glance

“…Up to now, a number of researches have been carried out to investigate the expression of Survivin and its relationship with apoptosis and proliferation in HCC. Homologous results show that there is a noticeable up-regulated expression of Survivin in HCC cells compared with that in adjacent cirrhosis tissues and normal tissues and increased protein expression level is markedly associated with the ratio of proliferative index to apoptotic index [52][53][54].…”

“…Objective researches implicate that Survivin protein can function as a dominant regulator of cell death and proliferation, controlling cell apoptosis through physically binding to downstream caspase-3 and caspase-7, and then inhibit activation of these proteins and/or act somewhere downstream of Bax and Fas-induced apoptosis signaling pathways to block Bax and Fas-induced apoptosis.This step can be suppressed by the X-linked IAP (XIAP) antagonist, Smac/DIABLO, which is released from the mitochondria and can relieve this inhibition and allow for apoptosis to proceed (Figure 1) [51,52]. Accordingly, thus it is reasonable to hypothesize that the over expression of Survivin is at least partially responsible for that malignant cells are able to escape from apoptosis and proliferate in a rapid manner.…”