KISS1methylation and expression as predictors of disease progression in colorectal cancer patients

Abstract

These data suggest that KISS1 is down-regulated in cancer tissues via promoter hypermethylation and therefore may represent a candidate target for treating metastatic CRC.

Aberrant methylated EDNRB can act as a potential diagnostic biomarker in sporadic colorectal cancer while KISS1 is controversial

“…14 Moreover, Chen et al declared that there is hypermethylation of this gene in 83.33% of primary CRC vs. 6.30% in normal intestine specimens and also there is an association with the depth of local invasion, tumor differentiation and tumor metastatic features. 15 In contrast, it is interesting that the present study using MS-HRM assay discovered no statistically significant differences between 3 0 flanking region methylation of tumor samples and adjacent tumor-free samples for KISS1; Table 3. The correlations of cilinicopathological characteristics of EDNRB and KISS1 gene methylation status.…”

“…30,31 It has been reported that EDNRB and KISS1 as the tumor suppressor and tumor metastasis suppressor genes, respectively, are silenced in various cancers such as colorectal cancer, which is caused by specific CpG islands' hypermethylation. [13][14][15] Regarding EDNRB, which encodes a G-protein coupled receptor, it is implicated that hypermethylation of CpG dinucleotides in 5 0 flanking region happens during CRC progression. 13 Indeed, this aberrant methylation is associated with the EDNRB downregulation and silencing that may be involved in the cell proliferation, 14,15 In the present study, EDNRB hypermethylation in CRC confirmed quantitatively for the first time by MS-HRM assay, concordant with what previously found in Chen et al study.…”

“…[13][14][15] Regarding EDNRB, which encodes a G-protein coupled receptor, it is implicated that hypermethylation of CpG dinucleotides in 5 0 flanking region happens during CRC progression. 13 Indeed, this aberrant methylation is associated with the EDNRB downregulation and silencing that may be involved in the cell proliferation, 14,15 In the present study, EDNRB hypermethylation in CRC confirmed quantitatively for the first time by MS-HRM assay, concordant with what previously found in Chen et al study. 13 Methylation specific PCR (MSP) results in their study, which is a non-quantitative technique, showed that EDNRB hypermethylation frequency in CRC tumor tissues was higher than adjacent normal samples (92.86 versus 59.52, P D 0.001) and this aberrant methylation was correlated with EDNRB downregulation.…”

“…25 It is demonstrated that KISS1 expression is low or reduced in transcriptional level in bladder cancer and CRC, which may be influenced by hypermethylation of CpG rich regions in 5 0 upstream and 3 0 downstream of KISS1 gene. 14,15,26 It is believed that kisspeptins serve as metastasis suppressors in some cancers, 25 however, this inhibition function is not clearly understood. Nonetheless, KISS1R activation through kisspeptins may lead to suppression of ERK activation, which culminates with a reduction in matrix metalloproteinase 9 (MMP-9) expression and ultimately inhibition of tumor metastasis.…”

“…For this reason, several studies have been performed and some of them non-quantitatively showed that EDNRB and KISS1 genes are subjected to methylation alterations in colorectal cancer. [13][14][15] Endothelin receptor type B (EDNRB) gene, which is mapped to chromosome region 13q22, encodes a receptor which is a member of the G-protein coupled receptor superfamily and involves normally in the development of embryonic and enteric ganglia. 13,16,17 The interaction of this receptor with endothelins leads to the releasing of InsP 3 and Ca 2C as second messengers.…”