S100A4 over-expression underlies lymph node metastasis and poor prognosis in colorectal cancer

e14029 Background: Slug plays a critical role in regulating the epithelial-mesenchymal transition (EMT) by down-regulation of epithelial markers and up-regulation of mesenchymal markers. The purpose of the present study was to evaluate the clinical significance of Slug and Vimentin expression in colorectal cancer (CRC) and to perform in vitro characterization of Slug’s function. Methods: At first, the biological role of Slug in CRC was assessed by RNA interference in CRC cell lines to assess tumor progression, invasion and migration. We next analyzed Slug and Vimentin expression in surgical tissue specimens from 181 CRC patients by quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Results: Knockdown of Slug in siRNA knockdown studies resulted in induction of EMT markers, inhibited cancer cell proliferation, invasion and migration abilities. Slug and Vimentin expression in cancer tissues was significantly higher in patients with high T stage, lymph node involvement, liver metastasis and advanced TNM stage. We also observed a significant correlation between Slug and Vimentin expression in CRC (rho = 0.467). Increased Slug and Vimentin expression were significantly associated with poor prognosis in Stage I-IV (p<0.0001, p=0.0005, log-rank test) and Stage II (p= 0.04, p=0.012, log-rank test) Furthermore, increased Slug expression was an independent predictive marker of lymph node metastasis (p=0.012) and prognostic factor (p= 0.025). Conclusions: Our data demonstrate that evaluation of Slug and Vimentin could be valuable in the identification of patients with lymph node metastasis or poor prognosis in CRC.

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RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.555 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 555-555

Author(s):

Hiroki Imaoka ◽

Yuji Toiyama ◽

Susumu Saigusa ◽

Koichiro Mori ◽

Tomofumi Noguchi ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Protein Expression ◽

Clinical Significance ◽

Poor Prognosis ◽

Cellular Proliferation ◽

Migration And Invasion ◽

Node Metastasis ◽

Potential Biomarker

555 Background: Rac GTPase activating protein (RacGAP) 1 plays a key role in controlling various cellular phenomena including cytokinesis, transformation and migration. Recently, the clinical significance of RacGAP1 expression has been reported in several malignancies. However, direct association between the RacGAP1 expression and colorectal cancer (CRC) has not been fully investigated. The aim of this study is to elucidate the function and clinical significance of RacGAP1 expression in CRC. Methods: 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 polymerase chain reaction. Then, we validated RacGAP1 protein expression using formalin-fixed paraffin-embedded samples from 298 CRC patients (Cohort 2) by immunohistochemistry. Finally, we evaluated the association between RacGAP1 mRNA and protein expression and clinicopathological data. Results: 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 TNM 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. Conclusions: 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.

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