title: Increased RhoA Activity Predicts Worse Overall Survival in Patients Undergoing Surgical Resection for Lauren Diffuse-Type Gastric Adenocarcinoma.
abstract: Several studies have reported a high rate of RHOA mutations in the Lauren diffuse-type gastric adenocarcinoma (GA) but not in intestinal-type GA. The aim of this study was to determine if RhoA activity is prognostic for overall survival (OS) in patients with resectable GA.
  
  
  
  Retrospective review was performed on a prospective database of GA patients who underwent potentially curative resection between 2003 and 2012 at a single institution. Tissue microarrays were constructed from surgical specimens and analyzed for phosphorylated RhoA, a marker of inactive RhoA signaling. OS was estimated by the Kaplan-Meier method, and multivariate analysis was performed by Cox proportional hazards regression modeling.
  
  
  
  One hundred thirty-six patients with diffuse-type GA and 129 patients with intestinal-type GA were examined. Compared to intestinal-type GA, diffuse-type GA tumors were significantly associated with increased tumor size and advanced tumor, node, metastasis (TNM) classification system stage. In patients with diffuse-type GA, high RhoA activity was associated with significantly worse OS when compared to low RhoA activity (5-year OS 52.5 vs. 81.0 %, p = 0.017). This difference in OS was not observed in patients with intestinal-type GA (5-year OS 83.9 vs. 81.6 %, p = 0.766). On multivariate analysis of diffuse-type GA patients, high RhoA activity was an independent negative prognostic factor for OS (hazard ratio 2.38, 95 % confidence interval 1.07-5.28).
  
  
  
  Increased RhoA activity is predictive of worse OS in patients with diffuse-type GA who undergo potentially curative surgical resection. Along with findings from genomic studies, these results suggest RhoA may be a novel therapeutic target in diffuse-type GA.
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Chang
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Soo-Jeong
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Changhwan
authors.initials: C
authors.lastname: Yoon
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
authors.forename: Do Joong
authors.initials: DJ
authors.lastname: Park
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. yoons@mskcc.org.
authors.forename: Sam S
authors.initials: SS
authors.lastname: Yoon
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D015996:Survival Rate; D046888:Tissue Array Analysis; D047368:Tumor Burden; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein