Prognostic value of CRM1in pancreas cancer

Abstract

Purpose: Pancreatic cancer is a highly aggressive malignant tumour with poor prognosis. The median survival is only 6 months. This study investigated the prognostic value of nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 (CRM1) expression in pancreas cancer. Methods: CRM1 expression was detected, by Western blot, in pancreatic tissue from 69 cancer patients and 10 normal subjects. Results: CRM1 showed increased expression in pancreatic cancer tissue (P = 0.007). The high expression of CRM1 was associated with increased serum levels of CEA (P = 0.002) and CA19-9 (P = 0.005). There was an association between CRM1 expression and tumour size (P = 0.01), lymphadenopathy (P = 0.004) and liver metastasis (P = 0.003). High CRM1 expression was not correlated with the other clinicopathological parameters. High CRM1 expression was a prognostic indicator for progression-free survival (PFS) (P = 0.006) as well as overall survival (OS) (P = 0.001). Expression of CRM1 was an independent prognostic parameter for poorer PFS and OS (95% CI, 1.27–5.39). Conclusions: CRM1 expression demonstrated prognostic value in pancreatic cancer. Prospective studies are required to determine the prognostic role of high expression of CRM1 in pancreatic cancer.

Phenethyl isothiocyanate suppresses the metastasis of ovarian cancer associated with the inhibition of CRM1-mediated nuclear export and mTOR-STAT3 pathway

“…9,15 mTOR is a cadre cargo of CRM1; the nucleocytoplasmic shuttling of mTOR were CRM1-dependent. 34 As a serine/threonine protein kinase, mTOR mediates nutrient-dependent intracellular signaling to ultimately govern a wide range of cellular processes, including cell growth, protein synthesis and differentiation.…”

“…[2][3][4][5][6][7] Up-regulated nuclear export and mislocalization of tumor suppressors are also relate to ovarian cancer metastasis. 8,9 Thus far there are no effective therapies targeting tumor metastasis, giving rationale to develop novel drugs targeting the metastasis-related signal pathways.…”

Increased UGT1A3 and UGT1A7 Expression is Associated with Pancreatic Cancer

“…The prognosis of patients with advanced stage pancreatic cancer is much worse than for those with early stage disease. Unfortunately, more than 80% of pancreatic cancer patients were in an advanced stage when diagnosed (Huang et al, 2009;Liu et al, 2014) U r i d i n e 5 ' -d i p h o s p h a t e ( U D P ) -glucuronosyltransferases (UGTs) are an important group of phase II drug metabolism enzymes in humans (Tukey and Strassburg, 2000). The human UDPglucuronosyltransferases (UGTs) are a superfamily ofThe UGT enzymes have been divided into two families of proteins termed UGT1 and UGT2, and three subfamilies of proteins termed UGT1A, UGT2A and UGT2B in human beings (Hanioka et al, 2012).…”

XPO1 Inhibition Enhances Radiation Response in Preclinical Models of Rectal Cancer

“…Most of these proteins are only functional, capable of preventing cancer initiation and progression, when they are properly localized inside the nucleus. However, they are often mutated, deleted, or aberrantly located within the cytosol in cancer cells; therefore, changes in the nuclear/cytoplasmic transport of these proteins can modify the survival and proliferation of cancer cells (18)(19)(20)(21). The XPO1 target survivin (also known as baculoviral IAP repeat containing 5, BIRC5) is a member of the inhibitor of apoptosis family (22), and it is considered as an important radiation resistance factor in rectal cancer (23)(24)(25)(26)(27)(28).…”