Rac
GTPase-activating protein (RacGAP) 1 plays a key role in controlling various cellular phenomena including cytokinesis, transformation, invasive migration and
metastasis. This study investigated the function and clinical significance of RacGAP1 expression in
colorectal cancer (CRC). The intrinsic functions of RacGAP1 in CRC cells were analyzed using
small interfering RNA (
siRNA). We analyzed RacGAP1
mRNA expression in surgical specimens from 193 CRC patients (Cohort 1) by real-time PCR. Finally, we validated RacGAP1
protein expression using
formalin-fixed
paraffin-embedded samples from 298 CRC patients (Cohort 2) by immunohistochemistry. Reduced RacGAP1 expression by
siRNA in CRC cell lines showed significantly decreased cellular proliferation, migration and invasion. In Cohort 1, RacGAP1 expression in CRC was significantly higher than in adjacent normal mucosa and increased according to
tumor node
metastasis stage progression. High RacGAP1 expression in
tumors was significantly associated with progression and prognosis. In Cohort 2, RacGAP1
protein was overexpressed mainly in the nuclei of CRC cells; however, its expression was scarcely observed in normal colorectal mucosa. RacGAP1
protein expression was significantly higher in CRC patients with higher T stage, vessel invasion and lymph node and distant
metastasis. Increased expression of RacGAP1
protein was significantly associated with poor disease-free and overall survival. Multivariate analyses revealed that high RacGAP1 expression was an independent predictive marker for
lymph node metastasis, recurrence and poor prognosis in CRC. Our data provide novel evidence for the
biological and clinical significance of RacGAP1 as a potential
biomarker for identifying patients with
lymph node metastasis and poor prognosis in CRC.