Our previous study reported that the DNA methylation of
growth hormone secretagogue receptor (GHSR) was significantly higher in
thymoma or
thymic carcinoma (TC) than in normal thymic tissue samples. Thymic epithelial
tumors (TETs) with higher GHSR DNA methylation were associated with significantly worse prognosis than those with lower levels of DNA methylation. Diversified components of the
ghrelin-GHSR axis may exert opposing effects in
cancer progression, depending on the
cancer type in question. However, the precise function of the axis remains unclear. In the present study, the
mRNA expression of five key components of the
ghrelin system [native
ligand ghrelin, variant
ligand In-1
ghrelin, native receptor GHSR1a, variant receptor GHSR1b and acylation
enzyme ghrelin O-
acyltransferase (GOAT)] were examined in 58 TET samples by reverse transcription-quantitative PCR, and
protein expression of GHSR1a and GHSR1b was assessed in 20 TETs using immunohistochemistry. The results revealed that In-1
ghrelin, GHSR1b (variant forms) and GOAT were more strongly expressed in
thymoma compared with thymic-adjacent tissue. By contrast, no significant differences were observed in the expression of
ghrelin and GHSR1a (native forms) between
thymoma and thymic tissue. The
mRNA expression of In-1
ghrelin and GHSR1b (variant forms) was positively associated with GHSR methylation in
thymoma tissue samples. However, a relationship was not found between
ghrelin, GHSR1a or GOAT expression (native forms) and GHSR methylation in
thymoma. Immunohistochemical analysis revealed that
mRNA expression of GHSR1a and GHSR1b generally correlated with expression of the corresponding
protein, and that the expression of GHSR1b was increased in advanced-stage TETs. These results indicate that the DNA methylation of GHSR is associated with a shift from native expression (
ghrelin and GHSR1a) to variant expression (In-1
ghrelin and GHSR1b), which induces the
tumorigenesis of
thymoma, but not TC.