Expression of MMP-9 and WAVE3 in colorectal cancer and its relationship to clinicopathological features.
OBJECTIVE
To investigate matrix metalloproteinase 9 (MMP-9) and WAVE3 expression in human colorectal cancer (CRC) and to evaluate their clinical significance.


METHODS
We first performed real-time PCR to evaluate mRNA expression of MMP-9 and WAVE3 in 21 pairs of fresh CRC samples matched with adjacent normal mucosa. Then, MMP-9 and WAVE3 proteins were evaluated by immunohistochemistry on CRC tissue microarrays which included 216 CRC specimens and corresponding normal colorectal mucosa, and their correlation with clinicopathological factors and overall survival after surgery was evaluated.


RESULTS
Both real-time PCR and immunohistochemistry evaluation have demonstrated that MMP-9 and WAVE3 were over-expressed in colorectal cancer tissues compared with normal mucosa (p < 0.001). MMP-9 expression was significantly higher in patients with low-grade differentiation and distant metastasis (p = 0.003 and p = 0.005, respectively), and patients with MMP-9-positive expression had a poorer prognosis (p = 0.008). However, patients with WAVE3-positive expression had a better prognosis (p = 0.039) and particularly favorable prognostic factors, including non-lymph node metastasis, non-distant metastasis, and early TNM stage (p = 0.029, 0.021, and 0.003, respectively). In addition, MMP-9-negative/WAVE3-positive patients had the best overall survival (p = 0.021). In multivariate survival analysis, MMP-9 expression and combined expression status of MMP-9/WAVE3 were identified as independent prognostic factors for CRC (p = 0.046 and p = 0.019, respectively).


CONCLUSIONS
Combined analysis of MMP-9 and WAVE3 has a significant value for assessing prognosis of CRC patients after surgery.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Hepato-Pancreato-Biliary Surgery, Peking University School of Oncology, Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing, 100142, China.
Yi
Y
Zhang
Xiao-Ya
XY
Guan
Bin
B
Dong
Min
M
Zhao
Jian-Hui
JH
Wu
Xiu-Yun
XY
Tian
Chun-Yi
CY
Hao
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D012333:RNA, Messenger; C120153:WASF3 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; D020780:Matrix Metalloproteinase 9