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KiSS-1 methylation and protein expression patterns contribute to diagnostic and prognostic assessments in tissue specimens for colorectal cancer
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KiSS-1 methylation and protein expression patterns contribute to diagnostic and prognostic assessments in tissue specimens for colorectal cancer
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Journal Article
KiSS-1 methylation and protein expression patterns contribute to diagnostic and prognostic assessments in tissue specimens for colorectal cancer
2013
Overview
KISS1
is a metastasis suppressor lost in several solid malignancies. We evaluated the clinical relevance of KiSS-1 methylation and its protein expression in colorectal cancer. The epigenetic silencing of KiSS-1 by hypermethylation was tested in colon cancer cells (
n
= 5) before and after azacytidine treatment. KiSS-1 methylation was evaluated by methylation-specific PCR in colorectal cancer cells, and normal, benign, and tumor tissues (
n
= 352) were grouped in a training set (
n
= 62) and two independent validation cohorts (
n
= 100 and
n
= 190). KiSS-1 protein expression was analyzed by immunohistochemistry on tissue arrays. KiSS-1 hypermethylation correlated with transcript and protein expression loss, being increased in vitro by azacytidine. Methylation rates were 53.1, 70.0, and 80.0 % in the training and validation sets, respectively. In the training set, KiSS-1 methylation rendered a diagnostic accuracy of 72.7 % (
p
= 0.002). Combination of KiSS-1 methylation and serum CEA (
p
= 0.001) increased the prognostic utility of CEA alone (
p
= 0.022). In the first validation set, KiSS-1 methylation correlated with tumor grade (
p
= 0.011), predicted recurrence (
p
= 0.009), metastasis (
p
= 0.004), disease-free (
p
= 0.034), and overall survival (
p
= 0.015). In the second validation cohort, KiSS-1 methylation predicted disease-specific survival (
p
= 0.030). In the training set, cytoplasmic KiSS-1 expression was significantly higher in nonneoplastic biopsies as compared to colorectal tumors (
p
< 0.0005). In the validation set, loss of cytoplasmic expression correlated with tumor stage (
p
= 0.007), grade (
p
= 0.035), recurrence (
p
= 0.017), and disease-specific survival (
p
= 0.022). KiSS-1 was revealed epigenetically modified in colorectal cancer. The diagnostic and prognostic utility of KiSS-1 methylation and expression patterns suggests their assessment for the clinical management of colorectal cancer patients.
Publisher
Springer Netherlands,Springer Nature B.V
