| Background Colorectal cancer (CRC) is one of the common malignancies worldwideand its incidence ranks third in the world among all kinds of malignant tumors. Inrecent years, the incidence of colorectal cancer has been on the rise in China and nowranks second malignancies, indicating it as a large threaten to the health of our people.Early detection, early diagnosis and early treatment of colorectal cancer are the key toreduce mortality and improve long-term survival of CRC. However, there is not asatisfactory tumor marker for colorectal cancer. Though carcinoembryonic antigen(CEA) is the mostwidely used clinical tumor marker for colorectal cancer, itsspecificity and sensitivity are not high and is regulatively used in the postoperativemonitoring and prognosis evaluation of patients with colorectal cancer. Therefore,looking for more and new tumor marker for colorectal cancer is critical to improvingthe early diagnosis, prognosis valuation and postoperative monitoring of colorectalcancer.WEE1is a nuclear kinase and belongs to the family of serine/threonine proteinkinase. WEE1has been shown to play an important role in maintain the integrity ofthe gene by inducing G2checkpoint blockage, which was carried out in cell mitosisbefore participate in the repair of damaged DNA. Because of the lack of the functionof P53, tumor cells often lack the G1checkpoint to repair the damaged DNA, onlyrely on the G2checkpoint. WEE1is one of the few known regulator of G2checkpointgene in human tumors, which has been found to play an important role in a variety oftumors, including in treatment of colorectal cancer. Recent studies have also foundthat WEE1is upregulated in a various of malignancies including malignantglioblastomas, seminoma, osteosarcoma, breast cancer, melanoma and squamous cellcarcinoma of the vulva. The high expression of WEE1is showed to be closely relatedto the metastasis and prognosis of melanoma, suggesting it as a potential tumormarker. However the expression level of WEE1in colorectal cancer and itsrelationship with clinicopathological features as well as prognosis of colorectal cancerhave not been reported before.Objective To investigate the WEE1gene and protein expression in colorectal cancertissues and explore the correlation between WEE1expression and clinicopathological features as well as prognosis of colorectal cancer.Methods:(1)44cases of colorectal cancer and its corresponding normal colorectalmucosa tissue were collected from patients underwent operation in our hospital.WEE1expression level in these tissue specimens was determined by quantitativereal-time polymerase chain reaction (qRT-PCR) and relationship between WEE1expression and clinicopathologic features of CRC patients was analyzed.(2)102cases of paraffin-embedded colorectal cancer specimens were collectedfrom the patients who underwent operation in our hospital from January2008toDecember2009. WEE1protein expression in102cases of CRC specimens wasdetermined by immunohistochemistry and all patients were subsequently divided intolow WEE1expression group (immunohistochemistry score of "0" or "1+") and highWEE1expression group (immunohistochemistry score of"2+"or"3+") accordingto the results of immunohistochemical. Survival curves of these two groups areplotted by Kaplan-Meier method and overall survival was compared by Log-rank test.In addition,1year,3years,5-year survival rates of the two groups are also comparedusing the life table method. Multivariate Cox proportional hazards regression modelwas also constructed to screen the independent prognostic risk factor for colorectalcancer.Results: The result of real-time PCR showed that WEE1gene expression in colorectalcancer tissues was significantly higher than that in the corresponding normal colonicmucosa tissues (0.392vs.0.297, P <0.0001), and WEE1gene was up-regulated in70.5%(31/44) colorectal cancer. Meanwhile, WEE1up-regulation was closely relatedto distant metastasis (P=0.036) and TNM stage (P=0.028) of colorectal cancer. Theresult of immunohistochemical showed that WEE1protein was positive in52.9%(54/102) of colorectal cancer tissues,102cases of colorectal cancer patients weretherefore divided into (n=29) and low WEE1expression group (n=73), the averagesurvival time of patients within high WEE1expression group was significantly shorterthan low WEE1expression group (50.6±5.6months vs.65.6±2.5months, P=0.034). One-year, three-year and five-year survival rate of patients within high WEE1expression group were69%,62%and58%, which were also lower than low WEE1expression group (90%,82%and77%; P=0.012). Multivariate Cox proportionalhazards regression model indicated that TNM stage (harzard rate [HR],5.126; P=0.024) and high WEE1expression (HR,3.339; P=0.039) were the independent riskfactors affecting the prognosis of patients with colorectal cancer. Conclusion: The expression of WEE1is up-regulated in colorectal cancer tissues andits high expression is closely related to high malignancy degree and poor prognosis ofCRC, suggesting WEE1as a novel prognostic biomarker for patients with CRC... |
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