NM23 as a prognostic biomarker in ovarian serous carcinoma

Abstract

The nm23 gene is a reported metastasis suppressor gene. Recent studies have shown that its expression has tissue specificity. The role of nm23 in human ovarian cancer is still controversial. This study examines the prognostic significance of nm23 expression in patients with serous ovarian carcinoma. Following comparative proteomics in 13 fresh frozen ovarian serous cancer tissues with other histological types of ovarian cancers, validation was performed using immunohistochemistry on clinically well-designed 73 ovarian serous carcinoma microarray samples that were retrieved from ovarian cancer patients from 1990 to 2003. Statistical analysis of the results was performed using v 2 test, Cox proportional regression, the Kaplan-Meier method and log-rank test. We found that the expression of nm23 inversely correlated with peritoneal seeding (P ¼ 0.009). However, strong nm23 expression was associated with mortality in patients with ovarian carcinoma in univariate analysis (P ¼ 0.04). Poor prognostic factors of disease-free survival included tumor residue more than 2 cm (P ¼ 0.02), bilaterality (P ¼ 0.01) and peritoneal seeding (Po0.01), whereas poor prognostic factors affecting overall survival included peritoneal seeding (P ¼ 0.05). In Kaplan-Meier analysis, strong nm23 immunoreactivity correlates with poor overall survival (P ¼ 0.04) but not with poor disease-free survival. In conclusion, overexpression of nm23 is independently associated with decreased overall survival in patients with ovarian carcinoma and also significantly correlates with mortality. Nm23 may have a biological function that leads to poor clinical outcomes in ovarian carcinoma.

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

“…The possible mechanisms include metastasis suppressor genes (Nm23, KISS1, KISS1R, KAI1, E-cadherin, OGR1, BRMS1), epithelialmesenchymal transition (EMT), tumor microenvironment, chemokines, and microRNA. [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.…”

Expressional Analyses of NM23-H1, KAI1 and MKK4 Metastasis-Related Genes in Metastatic Ovarian Carcinomas

“…Despite NM23-H1 and KAI1 genes have been described as metastasis suppressors, increased protein levels of these two genes in EOC have also been reported before. 7 On the other hand, due to lack of functional experimental data, there is no further explanation regarding their suppressor roles either in metastasis or in carcinogenesis of EOC. Nevertheless, our data showing increased mRNA levels of NM23-H1 and KAI1 genes in EOC may contribute to elucidate previous uncertain situations of these two genes in EOC.…”

“…17,18 On the other hand, metastasis suppressor roles of these three genes in ovarian cancer have been speculated by previous studies at the protein level. 7,12,15,19 A summary of the studies investigating the expression levels of NM23-H1, KAI1 and MKK4 genes in clinical samples are given in Table 3.…”

“…6 While reduced NM23-H1 protein level has been associated with peritoneal implants, over-expression has been related with distant metastasis of ovarian serous carcinoma. 7 Despite NM23-H1 has been considered as a metastasis suppressor, it has been described as a good prognostic marker in ovarian cancer and also as a poor prognostic marker in some other studies. 7,8 Because of conflicting results mentioned above, the role of NM23-H1 in ovarian carcinoma is still unclear.…”

“…7 Despite NM23-H1 has been considered as a metastasis suppressor, it has been described as a good prognostic marker in ovarian cancer and also as a poor prognostic marker in some other studies. 7,8 Because of conflicting results mentioned above, the role of NM23-H1 in ovarian carcinoma is still unclear. 9 The KAI1/CD82 gene, located at human chromosome 11p11.2 region, encodes a plasma membrane glycoprotein of 267 amino acids and belongs to the transmembrane 4 superfamily (TM4SF, Tetraspanins).…”