HGF/c-Met axis drives cancer aggressiveness in the neo-adjuvant setting of ovarian cancer

被引：31

作者：

Mariani, Marisa ^{[1
,2
]}

McHugh, Mark ^{[1
]}

Petrillo, Marco ^{[2
]}

Sieber, Steven ^{[1
]}

He, Shiquan ^{[1
]}

Andreoli, Mirko ^{[1
,2
]}

Wu, Zheyang ^{[3
]}

Fiedler, Paul ^{[1
]}

Scambia, Giovanni ^{[2
,4
]}

Shahabi, Shohreh ^{[1
]}

Ferlini, Cristiano ^{[1
,4
]}

机构：

[1] Danbury Hosp Res Inst, Danbury, CT 06810 USA

[2] Univ Cattolica Sacro Cuore, Dept Gynecol, I-00168 Rome, Italy

[3] Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA

[4] Jean Paul IInd Res Fdn, Dept Oncol, Campobasso, Italy

来源：

ONCOTARGET | 2014年 / 5卷 / 13期

关键词：

HGF; c-MET; Ovarian Cancer; Neo-Adjuvant Chemotherapy; HEPATOCYTE GROWTH-FACTOR; CROSS-TALK; C-MET; CHEMOTHERAPY; EXPRESSION; OVEREXPRESSION; PACLITAXEL; SURGERY; CELLS; HUR;

D O I：

10.18632/oncotarget.2049

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ovarian cancer is the most lethal gynecologic malignancy. Recently, NACT (Neo Adjuvant Chemotherapy) has been tested as alternative approach for the management of ovarian cancer patients. A biological predictor helpful in selecting patients for NACT would be desirable. This study was aimed at identifying actionable mechanisms of resistance to NACT. Expression of a panel of microRNAs was screened in a discovery set of 85 patients. Analysis of the potential targets was conducted in the same RNAs by calculating significant correlations between microRNAs and genes. Quantitative fluorescent immunohistochemistry was employed in a validation set of 109 patients. MiR-193a-5p was significantly overexpressed in the NACT setting. Analysis of its potential targets demonstrated that this microRNA is also significantly correlated with HGF and MET genes. Analysis of protein expression in samples taken before and after NACT demonstrated that both HGF and c-Met are increased after NACT. Patients who relapse shortly after NACT exhibited the highest relative basal expression of both HGF and c-Met, while the opposite phenomenon was observed in the best responders. Mir-193a-5p, HGF and c-Met expression may help select eligible patients for this modality of treatment. Moreover, inhibitors of this pathway may improve the efficacy of NACT.

引用

页码：4855 / 4867

页数：13

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