Increased RhoA activity predicts worse overall survival in patients undergoing surgical resection for Lauren diffuse-type gastric adenocarcinoma Journal Article
| Authors: | Chang, K. K.; Cho, S. J.; Yoon, C.; Lee, J. H.; Park, D. J.; Yoon, S. S. |
| Article Title: | Increased RhoA activity predicts worse overall survival in patients undergoing surgical resection for Lauren diffuse-type gastric adenocarcinoma |
| Abstract: | Background: 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. Methods: 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. Results: 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). Conclusions: 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. © 2016, Society of Surgical Oncology. |
| Journal Title: | Annals of Surgical Oncology |
| Volume: | 23 |
| Issue: | 13 |
| ISSN: | 1068-9265 |
| Publisher: | Springer |
| Date Published: | 2016-12-01 |
| Start Page: | 4238 |
| End Page: | 4246 |
| Language: | English |
| DOI: | 10.1245/s10434-016-5357-2 |
| PROVIDER: | scopus |
| PUBMED: | 27364501 |
| PMCID: | PMC5339626 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 6 December 2016 -- Source: Scopus |
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