Role of paxillin in colorectal carcinoma and its relationship to clinicopathological features.
BACKGROUND
Colorectal carcinoma is one of the most common malignant tumors. Despite advances in therapy, mortality is still very high. The aim of this study was to evaluate the expression of paxillin in the human colon adenocarcinoma cell line SW480 and its role in cell cycle and apoptosis. We also investigated the expression of paxillin in colorectal carcinoma tissues and its relationship to clinicopathological features and survival.


METHODS
Paxillin short hairpin RNA (shRNA) was constructed and transfected into the colon adenocarcinoma cell line SW480. The influence of paxillin shRNA on the cell cycle and cell apoptosis was analyzed by flow cytometry. Immunohistochemistry staining was used to assess the expression of paxillin and its association with the expression of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, p53 and Bcl-2 in 102 patients with primary colorectal carcinoma. Western blotting was also used to investigate the expression of paxillin. Medical records were reviewed and a clinicopathological analysis was performed.


RESULTS
In vitro, the percentage of cells in S phase was (45.23±1.05)%, (43.53±1.23)%, and (36.13±0.57)% in the blank control group, negative control group, and paxillin shRNA group respectively. It was significantly decreased in the paxillin shRNA group (P = 0.000). The early apoptosis index of the paxillin shRNA group (17.2±1.18%) was significantly increased compared to the control shRNA group ((13.17±1.15)%, P = 0.013). Paxillin was positive in 71 (69.6%) patients, and it was found to be overexpressed in tumor tissues compared with normal adjacent tissues. Paxillin positive rate was higher in patients who are less than 50-years old (100.0% vs. 65.6%, P = 0.016). Paxillin expression was associated with a high histologic grade of carcinoma (81.4% vs. 61.0%, P = 0.031), a high rate of regional lymph node metastasis (22.5% vs. 13.0%, P = 0.031), mesenteric artery lymph node metastasis (100.0% vs. 64.8%, P = 0.008), distant metastasis (94.1% vs. 64.7%, P = 0.016) and a high Tumor Node Metastasis (TNM) stage (94.1%, 73.2%, 60.0%, and 50%, P = 0.030). Multivariate analyses revealed that recurrence was associated with the rate of regional lymph node metastasis (P = 0.001) and paxillin expression (P = 0.024). Multivariate analysis indicated that the overall survival is related to the TNM stage (P = 0.000).


CONCLUSIONS
In vitro, paxillin may promote cell proliferation and inhibit apoptosis in SW480 cells. Paxillin may be a potential metastasis predictor, and an independent prognosis factor of recurrence. It may also be related to poor patient outcomes, but was not an independent predictor of survival.
Department of Pathology, Peking University First Hospital, Beijing 100034, China.
Hongfang
H
Yin
Department of General Surgery, Peking University First Hospital, Beijing 100034, China.
Quanwen
Q
Zhang
Department of General Surgery, Peking University First Hospital, Beijing 100034, China. Email: wangxin_guo@hotmail.com.
Xin
X
Wang
Department of Pathology, Peking University First Hospital, Beijing 100034, China.
Ting
T
Li
Department of General Surgery, Peking University First Hospital, Beijing 100034, China.
Yuanlian
Y
Wan
Department of General Surgery, Peking University First Hospital, Beijing 100034, China.
Yucun
Y
Liu
Surgical Laboratory, Peking University First Hospital, Beijing 100034, China.
Jing
J
Zhu
D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051419:Paxillin / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D051419:Paxillin; D034741:RNA, Small Interfering