Abstract
Systemic treatment of patients with early-stage cancers attempts to eradicate occult metastatic disease to prevent recurrence and increased morbidity. However, prediction of recurrence from an analysis of the primary tumor is limited because disseminated cancer cells only represent a small subset of the primary lesion. Here we analyze the expression of circulating microRNAs (miRs) in serum obtained pre-surgically from patients with early stage colorectal cancers. Groups of five patients with and without disease recurrence were used to identify an informative panel of circulating miRs using quantitative PCR of genome-wide miR expression as well as a set of published candidate miRs. A panel of six informative miRs (miR-15a, mir-103, miR-148a, miR-320a, miR-451, miR-596) was derived from this analysis and evaluated in a separate validation set of thirty patients. Hierarchical clustering of the expression levels of these six circulating miRs and Kaplan-Meier analysis showed that the risk of disease recurrence of early stage colon cancer can be predicted by this panel of miRs that are measurable in the circulation at the time of diagnosis (P = 0.0026; Hazard Ratio 5.4; 95% CI of 1.9 to 15).
Highlights
Colorectal cancer (CRC) is the third leading cause of cancer mortality that affects men and women
Approximately 1 in 4 patients with early stage disease will suffer from recurrence and biomarkers that identify patients at high risk at the time of initial diagnosis and surgery would allow to select those patients for closer monitoring and possibly systemic treatments ([3,4,5]; reviewed recently in [6])
The distinct function of miRs in different cancers has become more obvious over the past years [8,9], and many studies show that miR signatures can be used to distinguish different cancers [10,11,12,13], prognoses [14,15], reveal potential targets [16], altered signaling pathways [17], or malignant progression from in situ carcinoma to invasive disease [18]
Summary
Colorectal cancer (CRC) is the third leading cause of cancer mortality that affects men and women . Worldwide it accounts for approximately one million new cancers and one-half million deaths representing 10 percent of cancer deaths [1]. A previous study [21] using expression profiling of 315 miRs in tissues from stage II colon cancers showed differences in the patterns for recurrent disease. The expression levels of specific miRs in the tissues correlated with the probability of recurrencefree survival by multivariate analysis. These results suggest that perturbed expression of miRs in colon cancer may have a prognostic potential
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.
