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Increased RhoA Activity Predicts Worse Overall Survival in Patients Undergoing Surgical Resection for Lauren Diffuse-Type Gastric Adenocarcinoma

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

Funded in part through National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748.

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Authors and Affiliations

  1. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Kevin K. Chang MD, Soo-Jeong Cho MD, PhD, Changhwan Yoon PhD, Jun Ho Lee MD & Sam S. Yoon MD

  2. Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea

    Do Joong Park MD, PhD

Authors
  1. Kevin K. Chang MD
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  2. Soo-Jeong Cho MD, PhD
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  3. Changhwan Yoon PhD
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  4. Jun Ho Lee MD
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Correspondence to Sam S. Yoon MD.

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Chang, K.K., Cho, SJ., Yoon, C. et al. Increased RhoA Activity Predicts Worse Overall Survival in Patients Undergoing Surgical Resection for Lauren Diffuse-Type Gastric Adenocarcinoma. Ann Surg Oncol 23, 4238–4246 (2016). https://doi.org/10.1245/s10434-016-5357-2

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  • DOI: https://doi.org/10.1245/s10434-016-5357-2

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