CpG Island Methylator Phenotype May Predict Poor Overall Survival of Patients with Stage IV Colorectal Cancer

Kuo-Hsing Chen; Liang-In Lin; Li-Hui Tseng; Yu-Lin Lin; Jau-Yu Liau; Jia-Huei Tsai; Jin-Tung Liang; Been-Ren Lin; Ann-Lii Cheng; Kun-Huei Yeh

doi:10.1159/000493387

CpG Island Methylator Phenotype May Predict Poor Overall Survival of Patients with Stage IV Colorectal Cancer

Oncology. 2019;96(3):156-163. doi: 10.1159/000493387. Epub 2018 Dec 12.

Authors

Kuo-Hsing Chen^{1

2

3}, Liang-In Lin^{4

5}, Li-Hui Tseng⁶, Yu-Lin Lin^{1

3}, Jau-Yu Liau⁷, Jia-Huei Tsai⁷, Jin-Tung Liang⁸, Been-Ren Lin⁸, Ann-Lii Cheng^{1

9

2

3}, Kun-Huei Yeh^{10

11

12

13}

Affiliations

¹ Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan.
² National Taiwan University Cancer Center, Taipei City, Taiwan.
³ Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei City, Taiwan.
⁴ Department of Laboratory Medicine, National Taiwan University Hospital, Taipei City, Taiwan.
⁵ Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei City, Taiwan.
⁶ Department of Medical Genetics, National Taiwan University Hospital, Taipei City, Taiwan.
⁷ Department of Pathology, National Taiwan University Hospital, Taipei City, Taiwan.
⁸ Department of Surgery, National Taiwan University Hospital, Taipei City, Taiwan.
⁹ Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan.
¹⁰ Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan, [email protected].
¹¹ National Taiwan University Cancer Center, Taipei City, Taiwan, [email protected].
¹² Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei City, Taiwan, [email protected].
¹³ Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei City, Taiwan, [email protected].

PMID: 30540994
DOI: 10.1159/000493387

Abstract

Objective: We aimed to study the prognostic role of CpG island methylator phenotype (CIMP) in patients with different stages of colorectal cancer (CRC).

Material and methods: We analyzed CIMP in stage I-IV CRC specimens from patients who were diagnosed between 2005 and 2013. CIMP status was determined using a 5-gene MethyLight-based assay. The clinicopathologic characteristics were reviewed and the overall survival (OS) was compared between patients with CIMP-high CRC and those with CIMP-low/negative CRC.

Results: Among 450 CRC specimens with successfully determined CIMP statuses, 74 (16.4%) were CIMP-high CRC. Although there was no difference in OS between patients with CIMP-high and CIMP-low/negative CRC across all stages (p = 0.4526), intriguingly, patients with stage IV CIMP-high CRC had significantly worse OS than those with stage IV CIMP-low/negative CRC (p = 0.0047). In a multivariate analysis, CIMP status remained an independent prognostic factor for overall mortality (HR = 5.60, 95% CI: 2.12-14.79, p = 0.0005) in metastatic CRC after adjusting for clinicopathologic variables and anti-cancer therapies.

Conclusion: Our results revealed that the presence of CIMP independently predicts poor OS in patients with stage IV CRC.

Keywords: CpG island methylator phenotype; Overall survival; Stage IV colorectal cancer.

MeSH terms

Aged
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / mortality
Colorectal Neoplasms / pathology
CpG Islands*
DNA Methylation*
Female
Humans
Male
Microsatellite Instability
Middle Aged
Mutation
Neoplasm Staging
Prognosis
Proto-Oncogene Proteins B-raf / genetics
Proto-Oncogene Proteins p21(ras) / genetics
Survival Rate

Substances

KRAS protein, human
BRAF protein, human
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins p21(ras)