Title |
High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients
|
---|---|
Published in |
Clinical & Experimental Metastasis, October 2010
|
DOI | 10.1007/s10585-010-9355-7 |
Pubmed ID | |
Authors |
Boye Schnack Nielsen, Stine Jørgensen, Jacob Ulrik Fog, Rolf Søkilde, Ib Jarle Christensen, Ulla Hansen, Nils Brünner, Adam Baker, Søren Møller, Hans Jørgen Nielsen |
Abstract |
Approximately 25% of all patients with stage II colorectal cancer will experience recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is upregulated in several cancer types and has been associated with survival in colon cancer. In the present study we developed a robust in situ hybridization assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon and 67 stage II rectal cancer specimens. The miR-21 signal was revealed as a blue chromogenic reaction, predominantly observed in fibroblast-like cells located in the stromal compartment of the tumors. The expression levels were measured using image analysis. The miR-21 signal was determined as the total blue area (TB), or the area fraction relative to the nuclear density (TBR) obtained using a red nuclear stain. High TBR (and TB) estimates of miR-21 expression correlated significantly with shorter disease-free survival (p = 0.004, HR = 1.28, 95% CI: 1.06-1.55) in the stage II colon cancer patient group, whereas no significant correlation with disease-free survival was observed in the stage II rectal cancer group. In multivariate analysis both TB and TBR estimates were independent of other clinical parameters (age, gender, total leukocyte count, K-RAS mutational status and MSI). We conclude that miR-21 is primarily a stromal microRNA, which when measured by image analysis identifies a subgroup of stage II colon cancer patients with short disease-free survival. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Denmark | 5 | 4% |
United States | 2 | 1% |
India | 1 | <1% |
Egypt | 1 | <1% |
Malaysia | 1 | <1% |
Belgium | 1 | <1% |
Germany | 1 | <1% |
Spain | 1 | <1% |
Singapore | 1 | <1% |
Other | 0 | 0% |
Unknown | 120 | 90% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 39 | 29% |
Researcher | 39 | 29% |
Student > Master | 15 | 11% |
Student > Bachelor | 8 | 6% |
Other | 6 | 4% |
Other | 15 | 11% |
Unknown | 12 | 9% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 48 | 36% |
Medicine and Dentistry | 28 | 21% |
Biochemistry, Genetics and Molecular Biology | 19 | 14% |
Computer Science | 5 | 4% |
Chemical Engineering | 3 | 2% |
Other | 13 | 10% |
Unknown | 18 | 13% |