Abstract
BackgroundColorectal cancer (CRC) is one of the most common malignancies but the current therapeutic approaches for advanced CRC are less efficient. Thus, novel therapeutic approaches are badly needed. The purpose of this study is to investigate the involvement of nuclear protein kinase CK2 α subunit (CK2α) in tumor progression, and in the prognosis of human CRC.Methodology/Principal FindingsExpression levels of nuclear CK2α were analyzed in 245 colorectal tissues from patients with CRC by immunohistochemistry, quantitative real-time PCR and Western blot. We correlated the expression levels with clinicopathologic parameters and prognosis in human CRC patients. Overexpression of nuclear CK2α was significantly correlated with depth of invasion, nodal status, American Joint Committee on Cancer (AJCC) staging, degree of differentiation, and perineural invasion. Patients with high expression levels of nuclear CK2α had a significantly poorer overall survival rate compared with patients with low expression levels of nuclear CK2α. In multi-variate Cox regression analysis, overexpression of nuclear CK2α was proven to be an independent prognostic marker for CRC. In addition, DLD-1 human colon cancer cells were employed as a cellular model to study the role of CK2α on cell growth, and the expression of CK2α in DLD-1 cells was inhibited by using siRNA technology. The data indicated that CK2α-specific siRNA treatment resulted in growth inhibition.Conclusions/SignificanceTaken together, overexpression of nuclear CK2α can be a useful marker for predicting the outcome of patients with CRC.
Highlights
Colorectal cancer (CRC) accounted for about 1 million new cases in 2002 (9.4% of the world total), and unlike most sites, numbers were not so different in men and women [1]
We investigated the expression of nuclear CK2 a subunit (CK2a) in 245 CRC patients by immunohistochemistry, and in four patients by Western blot
Elevated CK2a mRNA level has been reported in several human cancers, including melanoma and lung cancer [32,33]
Summary
Colorectal cancer (CRC) accounted for about 1 million new cases in 2002 (9.4% of the world total), and unlike most sites, numbers were not so different in men and women (ratio, 1.2:1) [1]. CRC ranks fourth in frequency in men and third in women. The highest incidence rates are in North America, Western Europe, and, in men especially, Japan. In Taiwan, CRC ranks as the second most frequently diagnosed malignancy and causes more than 10000 deaths annually (http://www.doh.gov.tw/statistic/index.htm; accessed in December 2008). In spite of the current surgical techniques and chemotherapy that have made significant improvements, the cure rate for advanced CRC remains low and the morbidity remains high [2]. Colorectal cancer (CRC) is one of the most common malignancies but the current therapeutic approaches for advanced CRC are less efficient. The purpose of this study is to investigate the involvement of nuclear protein kinase CK2 a subunit (CK2a) in tumor progression, and in the prognosis of human CRC
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