Abstract
Undetected micrometastasis plays a key role in the metastasis of cancer in colorectal cancer (CRC) patients. The aim of this study is to identify a biomarker of CRC patients with liver metastasis through the detection of circulating tumor cells (CTCs). Microarray and bioinformatics analysis of 10 CRC cancer tissue specimens compared with normal adjacent tissues revealed that 31 genes were up-regulated (gene expression ratio of cancer tissue to paired normal tissue > 2) in the cancer patients. We used a weighted enzymatic chip array (WEnCA) including 31 prognosis-related genes to investigate CTCs in 214 postoperative stage I–III CRC patients and to analyze the correlation between gene expression and clinico-pathological parameters. We employed the immunohistochemistry (IHC) method with polyclonal mouse antibody against DVL1 to detect DVL1 expression in 60 CRC patients. CRC liver metastasis occurred in 19.16% (41/214) of the patients. Using univariate analysis and multivariate proportional hazards regression analysis, we found that DVL1 mRNA overexpression had a significant, independent predictive value for liver metastasis in CRC patients (OR: 5.764; 95% CI: 2.588–12.837; p < 0.0001 on univariate analysis; OR: 3.768; 95% CI: 1.469–9.665; p = 0.006 on multivariate analysis). IHC staining of the immunoreactivity of DVL1 showed that DVL1 was localized in the cytoplasm of CRC cells. High expression of DVL1 was observed in 55% (33/60) of CRC tumor specimens and was associated significantly with tumor depth, perineural invasion and liver metastasis status (all p < 0.05). Our experimental results demonstrated that DVL1 is significantly overexpressed in CRC patients with liver metastasis, leading us to conclude that DVL1 could be a potential prognostic and predictive marker for CRC patients.
Highlights
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second most diagnosed in females worldwide, with over 1.2 million new cases each year and 608,700 estimated deaths [1]
We utilized ten colorectal cancer (CRC) cancer tissue specimens compared with their normal adjacent tissues
The 1301 overexpressed genes were analyzed with DAVID (Database for Annotation, Visualization, and Integrated Discovery) [18], and results indicated that a total of 31 genes were up regulated and associated with CRC carcinogenesis and prognosis
Summary
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second most diagnosed in females worldwide, with over 1.2 million new cases each year and 608,700 estimated deaths [1]. The clinical stage at diagnosis, site of lesion (rectum vs colon), invasion of contiguous organs and presence of perforation are positive predictive factors for postoperative CRC recurrence [2]. There have been significant improvements in the treatment of advanced CRC as a result of using a multidisciplinary approach, individuals with postoperative recurrence or metastatic disease still have poor prognosis [2]. Metastasis is the main cause of death from such tumors, the mechanism of the metastatic process in CRC is very complex and still not completely understood [7]. Novel and well-characterized biomarkers would be helpful for clinicians to predict metastatic progression and prognosis of CRC patients for facilitation of therapeutic intervention
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
