Opposing prognostic roles of nuclear and cytoplasmic RACGAP1 expression in colorectal cancer patients.
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.
Department of Surgical Pathology, Changhua Christian Hospital, Changhua 50006, Taiwan; Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 35664, Taiwan.
Chung-Min
CM
Yeh
Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 35664, Taiwan; School of Medicine, Chung Shan Medical University, Taichung 40242, Taiwan; Department of Medical Education, Chung Shan Medical University Hospital, Taichung 40242, Taiwan.
Wen-Wei
WW
Sung
Department of Surgery, Changhua Christian Hospital, Changhua 50006, Taiwan; School of Medicine, National Yang Ming University, Taipei 11221, Taiwan.
Hung-Wen
HW
Lai
Cancer Research Center, Changhua Christian Hospital, Changhua 50006, Taiwan; School of Optometry, Chung Shan Medical University, Taichung 40242, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung 40242, Taiwan.
Ming-Ju
MJ
Hsieh
School of Medicine, Chung Shan Medical University, Taichung 40242, Taiwan; Department of Gastroenterology, Changhua Christian Hospital, Changhua 50006, Taiwan.
Hsu-Heng
HH
Yen
Department of Surgical Pathology, Changhua Christian Hospital, Changhua 50006, Taiwan.
Tzu-Cheng
TC
Su
Department of Surgical Pathology, Changhua Christian Hospital, Changhua 50006, Taiwan.
Wei-Hsiang
WH
Chang
Department of Surgical Pathology, Changhua Christian Hospital, Changhua 50006, Taiwan.
Chia-Yu
CY
Chen
Institute of Medicine, Chung Shan Medical University, Taichung 40242, Taiwan; Department of Medical Oncology and Chest Medicine, Chung Shan Medical University Hospital, Taichung 40242, Taiwan.
Jiunn-Liang
JL
Ko
Department of Surgical Pathology, Changhua Christian Hospital, Changhua 50006, Taiwan; Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 35664, Taiwan; School of Medicine, Chung Shan Medical University, Taichung 40242, Taiwan. Electronic address: 132540@cch.org.tw.
Chih-Jung
CJ
Chen
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002467:Cell Nucleus / Q000737:chemistry*; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D003593:Cytoplasm / Q000737:chemistry*; D005260:Female; D020690:GTPase-Activating Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D020690:GTPase-Activating Proteins; C115995:mgcRacGAP
Colorectal cancer; MgcRacGAP; Prognosis; RACGAP1; Survival