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Archive > Volume 22 Issue 4 > 2015,22(4):465-471. DOI:10.3872/j.issn.1007-385X.2015.04.010 Prev Next
Clinical Research
Molecular profiling of colorectal cancer with CpG island methylation phenotype (CIMP) by using droplet digital PCR
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Abstract:
Objective:To investigate the clinicopathologic features of colorectal cancers with CpG island methylation phenotype (CIMP) by using droplet digital PCR, and to evaluate the feasibility of determining the CIMP status using plasma free DNA. Methods: Two hundred sixteen tumor and paired plasma samples were collected from patients with colorectal cancer enrolled into Changhai Hospital from 2008 to 2012. DNA was extracted from tumor tissues and plasmas and underwent bisulfate conversion. CIMP was determined by using digital PCR for the five genes CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1. P53 mutation was detected by immunohistochemical analysis. K-RAS and BRAF mutations were assessed by nest PCR. Results: Among the 216 colorectal cancers, 17 (7.9%) had BRAF mutations, 96 (44.4%) contained K-RAS mutations, 112 (51.9%) were P53- IHC (+), and 68 (31.5%) were CIMP positive (≧3 gene loci were hypermethylated). Most of the cancers with BRAF mutation (82.3%, 14/17) were CIMP(+), whereas only 94% (9/96) of the cancer with K-RAS mutations and 7.1% (8/112) of cancers harboring P53 mutations (+) were CIMP(+). Compared to CIMP(-) tumors, the unique clinical pathological features of the CIMP(+) tumors included: (1) more likely to happen in the proximal locations; (2) more likely to be mucinous carcinoma; (3) higher degree of differentiation. The overall survival period of colorectal patients with CIMP(+) was significantly shorter than that with CIMP(-). When plasma free DNA from these patients was used for CIMP analysis, the consistency, sensitivity and specificity were 93.4%, 87.2% and 100% respectively compared with the assay using tumor DNA.Conclusion: Patients with CIMP(+) colorectal cancer have unique clinical pathological characteristics and poor prognosis. When tumor tissues are not available, CIMP analysis with plasma free DNA using digital PCR is a feasible alternative.
Keywords:
droplet digital PCR ; CpG island methylation phenotype（CIMP） ; colorectal cancer ; plasma free DNA
Project Supported:
Project supported by the National Natural Science Foundation of China (No.81472770，81272280)
