Expression of uPAR mRNA in peripheral blood is a favourite marker for metastasis in gastric cancer cases

Abstract

Urokinase-type plasminogen activator receptor (uPAR) plays a central role in the plasminogen activation cascade and participates in extracellular matrix degradation, cell migration and invasion. We evaluated the expression level of uPAR mRNA and the presence of isolated tumour cells (ITCs) in bone marrow (BM) and peripheral blood (PB) in gastric cancer patients and clarified its clinical significance. We assessed specific uPAR mRNA expression by quantitative real-time reverse transcriptase-polymerase chain reaction (RT -PCR) in BM and PB in 846 gastric cancer patients as well as three epithelial cell markers, carcinoembryonic antigen (CEA), cytokeratin (CK)-19 and CK-7. The uPAR mRNA expression in bone marrow and peripheral blood expressed significantly higher than normal controls (Po0.0001). The uPAR mRNA in BM showed concordant expression with the depth of tumour invasion, distant metastasis, and the postoperative recurrence (P ¼ 0.015, 0.044 and 0.010, respectively); whereas in PB, we observed more intimate significant association between uPAR expression and clinicopathologic variables, such as depth of tumour invasion, the distant metastasis, the venous invasion and the clinical stage (P ¼ 0.009, 0.002, 0.039 and 0.008, respectively). In addition, the uPAR mRNA expression in PB was an independent prognostic factor for distant metastasis by multivariate analysis. We disclosed that it was possible to identify high-risk patients for distant metastasis by measuring uPAR mRNA especially in peripheral blood at the timing of operation in gastric cancer patients.

Clinical significance of circulating tumor cells in blood from patients with gastric cancer

“…These results suggest that sensitivity of CEA mRNA levels is higher than those of serum CEA levels. Furthermore, in a large‐scale study on 846 patients with stages I–IV gastric cancer, Kita et al 27. reported that positivity for CTC using a qRT‐PCR assay with the urokinase‐type plasminogen activator receptor was 47.8% (404/846).…”

La importancia del sistema activador de plasminógeno en la patogénesis y progresión del cáncer gástrico

“…The relation between expression of components of the PA system, especially uPAR, and clinico-pathological aspects has been explored in GC (Heiss et al, 1995b;Kawasaki et al, 1998;Zhao, Wang, Qu, Huang, & Wang, 2002;Kaneko, Konno, Baba, Tanaka, & Nakamura, 2003;Lee et al, 2004;Zhang, Zhao, Ru, & Ma, 2006;Kita et al, 2009;Alpízar-Alpízar et al, 2012;Guo, Ling, Ma, Zhou, & Zhao, 2015). One of the parameters consistently correlated with the expression of the members of this system is patient survival, which is generally shorter in patients with elevated expression, particularly of uPAR (Table 1).…”

The clinical significance of circulating tumor cells in gastrointestinal cancer

“…It is also well known that there is discordance of expression profi le between CTCs and primary tumor, and several markers for regulating metastasis and prognosis have been determined by PCR-based methods. [34][35][36][37] Furthermore, a comprehensive molecular profi ling using the cDNA microarray was performed to identify novel genes to predict gastric cancer metastasis, recurrence and prognosis, suggesting that expression of MT1-MMP in peripheral blood identifi ed by the cDNA microarray technique in gastric cancer was a powerful indicator of distant metastasis, especially for peritoneal dissemination. [38] van de Stolpe et al [39] reported that CTCs were heterogeneous and differed among different cancer types.…”