IGFBP-3 gene methylation in primary tumor predicts recurrence of stage II colorectal cancers Journal Article
| Authors: | Fu, T.; Pappou, E. P.; Guzzetta, A. A.; De Freitas Calmon, M.; Sun, L.; Herrera, A.; Li, F.; Wolfgang, C. L.; Baylin, S. B.; Iacobuzio-Donahue, C. A.; Tong, W.; Ahuja, N. |
| Article Title: | IGFBP-3 gene methylation in primary tumor predicts recurrence of stage II colorectal cancers |
| Abstract: | Objectives: To evaluate the influence of IGFBP-3 methylation on recurrence in patients with stage II colorectal cancer (CRC) from 2 independent cohorts. Background: The relationship between IGFBP-3 methylation in primary tumors (PTs) or lymph nodes (LNs) and risk of recurrence in patients with stage II CRC treated with surgery alone is unknown. Methods: IGFBP-3 methylation of DNA from 115 PTs and 1641 LNs in patients with stage II CRC from 2 independent cohorts was analyzed. Forty patients developed recurrence, whereas 75 matched patients remained recurrence free for more than 2 years after surgery. Cox proportional hazard models were used to calculate hazard ratios (HRs) of recurrence, adjusted for patient and tumor characteristics. Results: Methylation of IGFBP-3 in PTs was identified to be significantly associated with risk of recurrence in the training set. The signature was tested in a validation set and classified 40.7% of patients as high risk. Five-year recurrence-free survival rates were 76.4% and 58.3% for low-and high-risk patients, respectively, with an HR of 2.21 (95% confidence interval, 1.04- 4.68; P = 0.039). In multivariate analysis, the signature remained the most significant prognostic factor, with an HR of 2.40 (95% confidence interval, 1.10-5.25; P = 0.029). A combined analysis of 1641 LNs from the 2 sets identified IGFBP-3 methylation in LNs was not associated with risk of recurrence. Conclusions: Detection of IGFBP-3 methylation in PTs, but not in LNs, provides a powerful tool for the identification of patients with stage II CRC at high risk of recurrence. © 2015 Wolters Kluwer Health, Inc. All rights reserved. |
| Keywords: | cancer survival; clinical article; controlled study; human tissue; aged; primary tumor; methylation; cancer recurrence; cancer staging; follow up; sensitivity and specificity; colorectal cancer; tumor differentiation; cohort analysis; recurrence; dna methylation; high risk patient; k ras protein; somatomedin binding protein 3; receiver operating characteristic; mucin; recurrence free survival; low risk patient; lymph vessel metastasis; human; male; female; priority journal; article; igfbp-3 |
| Journal Title: | Annals of Surgery |
| Volume: | 263 |
| Issue: | 2 |
| ISSN: | 0003-4932 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2016-02-01 |
| Start Page: | 337 |
| End Page: | 344 |
| Language: | English |
| DOI: | 10.1097/sla.0000000000001204 |
| PROVIDER: | scopus |
| PMCID: | PMC4648704 |
| PUBMED: | 25822686 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 March 2016 -- Source: Scopus |
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