TY - JOUR
T1 - Prognostic value of CpG island methylator phenotype among colorectal cancer patients
T2 - A systematic review and meta-analysis
AU - Juo, Y. Y.
AU - Johnston, F. M.
AU - Zhang, D. Y.
AU - Juo, H. H.
AU - Wang, H.
AU - Pappou, E. P.
AU - Yu, T.
AU - Easwaran, H.
AU - Baylin, S.
AU - van Engeland, M.
AU - Ahuja, Nita
N1 - Funding Information:
This paper was supported by grants from National Cancer Institute K23 CA127141 (NA), the American College of Surgeons/ Society of University Surgeons (NA).
Publisher Copyright:
© The Author 2014.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Background: Divergent findings regarding the prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) patients exist in current literature. We aim to review data from published studies in order to examine the association between CIMP and CRC prognosis. Materials and methods: A comprehensive search for studies reporting disease-free survival (DFS), overall survival (OS), or cancer-specific mortality of CRC patients stratified by CIMP is carried out. Study findings are summarized descriptively and quantitatively, using adjusted hazard ratios (HRs) as summary statistics. Results: Thirty-three studies reporting survival in 10 635 patients are included for review. Nineteen studies provide data suitable for meta-analysis. The definition of CIMP regarding gene panel, marker threshold, and laboratory method varies across studies. Pooled analysis shows that CIMP is significantly associated with shorter DFS (pooled HR estimate 1.45; 95% confidence interval (CI) 1.07-1.97, Q= 3.95, I2 = 0%) and OS (pooled HR estimate 1.43; 95% CI 1.18-1.73, Q=4.03, I2=0%) among CRC patients irrespective of microsatellite instability (MSI) status. Subgroup analysis of microsatellite stable (MSS) CRC patients also shows significant association between shorter OS (pooled HR estimate 1.37; 95% CI 1.12-1.68, Q= 4.45, I2 = 33%) and CIMP. Seven studies have explored CIMP's value as a predictive factor on stage II and III CRC patient's DFS after receiving adjuvant 5-fluorouracil (5-FU) therapy: Of these, four studies showed that adjuvant chemotherapy conferred a DFS benefit among CIMP(+) patients, one concluded to the contrary, and two found no significant correlation. Insufficient data was present for statistical synthesis of CIMP's predictive value among CRC patients receiving adjuvant 5-FU therapy. Conclusion: CIMP is independently associated with significantly worse prognosis in CRC patients. However, CIMP's value as a predictive factor in assessing whether adjuvant 5-FU therapy will confer additional survival benefit to CRC patients remained to be determined through future prospective randomized studies.
AB - Background: Divergent findings regarding the prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) patients exist in current literature. We aim to review data from published studies in order to examine the association between CIMP and CRC prognosis. Materials and methods: A comprehensive search for studies reporting disease-free survival (DFS), overall survival (OS), or cancer-specific mortality of CRC patients stratified by CIMP is carried out. Study findings are summarized descriptively and quantitatively, using adjusted hazard ratios (HRs) as summary statistics. Results: Thirty-three studies reporting survival in 10 635 patients are included for review. Nineteen studies provide data suitable for meta-analysis. The definition of CIMP regarding gene panel, marker threshold, and laboratory method varies across studies. Pooled analysis shows that CIMP is significantly associated with shorter DFS (pooled HR estimate 1.45; 95% confidence interval (CI) 1.07-1.97, Q= 3.95, I2 = 0%) and OS (pooled HR estimate 1.43; 95% CI 1.18-1.73, Q=4.03, I2=0%) among CRC patients irrespective of microsatellite instability (MSI) status. Subgroup analysis of microsatellite stable (MSS) CRC patients also shows significant association between shorter OS (pooled HR estimate 1.37; 95% CI 1.12-1.68, Q= 4.45, I2 = 33%) and CIMP. Seven studies have explored CIMP's value as a predictive factor on stage II and III CRC patient's DFS after receiving adjuvant 5-fluorouracil (5-FU) therapy: Of these, four studies showed that adjuvant chemotherapy conferred a DFS benefit among CIMP(+) patients, one concluded to the contrary, and two found no significant correlation. Insufficient data was present for statistical synthesis of CIMP's predictive value among CRC patients receiving adjuvant 5-FU therapy. Conclusion: CIMP is independently associated with significantly worse prognosis in CRC patients. However, CIMP's value as a predictive factor in assessing whether adjuvant 5-FU therapy will confer additional survival benefit to CRC patients remained to be determined through future prospective randomized studies.
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U2 - 10.1093/annonc/mdu149
DO - 10.1093/annonc/mdu149
M3 - Review article
C2 - 24718889
AN - SCOPUS:84984879041
SN - 0923-7534
VL - 25
SP - 2314
EP - 2327
JO - Annals of Oncology
JF - Annals of Oncology
IS - 12
ER -