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Methylation of p14ARF and abnormal expression of p53 and
mdm2 in colorectal cancer: Role and correlation
Chaoliang Xiong, Jun Li, Lingxian Yan,
Yuan Huang*
Department of Gastroenterology, The Second Affiliated
Hospital of Nanchang University, Nanchang 330006, China.
*Corresponding author. E-mail:
huang9815@yahoo.com,
doc1998@yeah.net.
Accepted 14 June, 2010 |
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Methylation of p14ARF in 42 samples of colorectal cancer and
matched adjacent normal tissues was evaluated by methylation-specific
PCR (MSP) method. Expressions of p53 and mdm2 were detected
by using the semi-quantitative RT-PCR. Protein expressions
of p14ARF, p53 and mdm2 in the two groups were assessed with
immunohistochemical staining. Research data were analyzed
with Student’s t-test, chi-square test and Spearman rank
correlation. p14ARF methylation was identified in 19 (45.2%)
of 42 samples of colorectal cancer tissues and none of the
42 (0%) samples of normal adjacent tissues, indicating a
statistically significant difference between the two groups
(p <0.05). Positive protein expression rates of p14ARF, p53
and mdm2 in 42 samples of colorectal cancer tissues were
16.7, 73.8 and 54.5%, respectively, while were 95.2, 11.9
and 28.6% in normal adjacent tissues. A statistically
significant difference was noted between the two groups (p
<0.05) regarding protein expression of three genes. Protein
expressions of mdm2 and p53 were positively correlated (r =
0.423; p <0.05), and protein expression of both was
negatively correlated with p14ARF protein expression. p14ARF
methylation or protein expressions of p53 plus mdm2 were not
correlated with the age, sex or tumor size in patients with
colorectal cancer, but were positively correlated with tumor
differentiation and lymph node metastasis. p14ARF
methylation is closely correlated with colorectal cancer and
may be an early event in its occurrence; p14ARF methylation
and abnormal expression of mdm2 plus p53 play a major role
in occurrence and development of colorectal cancer. As the
p53-dependent pathway is one of the major regulation
channels for growth of colorectal epithelial cells,
simultaneous assessment of p14ARF methylation and abnormal
expression of MDM2 plus p53 may work as a biological
indicator for early diagnosis of colorectal cancer.
Key words:
Colorectal cancer, p14ARF, methylation, p53, mdm2, p53
protein, mdm2 protein, immunohistochemistry.
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