An inverse correlation between Interleukin-6 and select gene promoter methylation in patients with gastric cancer.
BACKGROUND
Both serum IL-6 levels and CpG island methylation have been shown to have prognostic significance in gastric cancer, it was suggested that an important link existed between IL-6 and methylation of cancers.


OBJECTIVE
To investigate the prognostic value of IL-6 serum level and the association between serum IL-6 levels and CpG island methylation at p16, DAPK, MGMT and E-cadherin in patients with gastric cancer.


METHODS
Methylation status was assessed by MSP in 75 surgical specimens of gastric adenocarcinoma. IL-6 serum levels were measured by chemiluminescent enzyme immunoassay (CLEIA).


RESULTS
Methylation of p16, DAPK, MGMT, and E-cadherin were present in 53, 48, 32, and 59% of patients. Patients with tumors methylated at p16 and DAPK had lower serum levels of IL-6 compared to unmethylated tumors (1.8 vs. 4.8 pg/ml, p = 0.01 for p16; 1.5 vs. 6.2 pg/ml, p = 0.0001 for DAPK). But there was no difference with MGMT and E-cadherin methylation status. Serum IL-6 levels were also associated with TNM stage (p = 0.001), depth of tumor invasion (p = 0.002), lymphatic invasion (p = 0.01), vascular invasion (p = 0.008), metastasis (p = 0.002) and signet cell histology (p = 0.001).


CONCLUSIONS
IL-6 is of prognostic value for patients of gastric cancer. Low serum IL-6 levels were associated with p16 or DAPK gene methylation in patients with gastric cancer.
Tang
Li Ping
LP
Department of Medicine, University of Hong Kong, Hong Kong, SAR, China.
Cho
Chi Hin
CH
Hui
Wai Mo
WM
Huang
Camy
C
Chu
Kent Man
KM
Xia
Harry H X
HH
Lam
Shiu Kum
SK
Rashid
Asif
A
Wong
Benjamin C Y
BC
Chan
Annie On On
AO
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D015254:DNA Modification Methylases; D045643:DNA Repair Enzymes; D064550:Death-Associated Protein Kinases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics; D025521:Tumor Suppressor Proteins
D051017:Apoptosis Regulatory Proteins; D015820:Cadherins; D015850:Interleukin-6; D025803:Tumor Suppressor Protein p14ARF; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D045643:DNA Repair Enzymes