Opposing prognostic roles of nuclear and cytoplasmic RACGAP1 expression in colorectal cancer patients.

Abstract

Rac GTPase activating protein 1 (RACGAP1) plays a regulatory role in initiation of cytokinesis, control of cell growth and differentiation, and tumor malignancy, making it a potential prognostic biomarker. RACGAP1 is present in the nucleus, but a diffuse distribution in the cytoplasm also occurs. The aim of this study was to determine the impact of nuclear and cytoplasmic expression of RACGAP1 on clinical outcome to provide further evidence of a role in colorectal cancer. RACGAP1 expression was analyzed by immunohistochemistry in 166 cancer specimens from primary colorectal cancer patients. The mean follow-up time after surgery was 5.4 years (range, 0.01-13.10 years). The prognostic value of RACGAP1 on overall survival was validated by Kaplan-Meier analysis and Cox regression models. RACGAP1 is expressed in colorectal specimen and is present in both the nucleus and cytoplasm in different amounts. Colorectal cancer patients had opposite prognoses depending on the site of RACGAP1 expression. Patients with high nuclear RACGAP1 expression had poor outcomes, whereas those with high cytoplasmic RACGAP1 expression had favorable prognosis (P = .003 and P = .001, respectively). Patients with low nuclear but high cytoplasmic RACGAP1 expression had better survival compared with those with other combinations (P < .001). We suggest that RACGAP1 expression levels in the nucleus and cytoplasm, determined by immunohistochemical staining, predict opposite clinical outcomes and that both could be independent prognostic markers for colorectal cancer.

• Authors: Chung-Min Yeh, Wen-Wei Sung, Hung-Wen Lai, Ming-Ju Hsieh, Hsu-Heng Yen, Tzu-Cheng Su, Wei-Hsiang Chang, Chia-Yu Chen, Jiunn-Liang Ko, Chih-Jung Chen
• Journal: Human pathology (Hum Pathol) Vol. 47 Issue 1 Pg. 45-51 (Jan 2016) ISSN: 1532-8392 [Electronic] United States
• PMID: 26508373 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• GTPase-Activating Proteins
• mgcRacGAP

Topics

• Aged
• Biomarkers, Tumor (analysis)
• Cell Nucleus (chemistry)
• Colorectal Neoplasms (chemistry, mortality, pathology, surgery)
• Cytoplasm (chemistry)
• Female
• GTPase-Activating Proteins (analysis)
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Predictive Value of Tests
• Proportional Hazards Models
• Time Factors
• Tissue Array Analysis
• Treatment Outcome