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Potential diagnostic and prognostic values of detecting promoter hypermethylation in the serum of patients with gastric cancer.

Leung WK, To KF, Chu ES, Chan MW, Bai AH, Ng EK, Chan FK, Sung JJ - Br. J. Cancer (2005)

Bottom Line: DNA was extracted from the pretherapeutic serum of 60 patients with confirmed gastric adenocarcinoma and 22 age-matched noncancer controls.Promoter hypermethylation in 10 tumour-related genes (APC, E-cadherin, GSTP1, hMLH1, MGMT, p15, p16, SOCS1, TIMP3 and TGF-beta RII) was determined by quantitative methylation-specific PCR (MethyLight).Moreover, patients with stages III/IV diseases tended to have higher concentrations of methylated APC (P = 0.08), TIMP3 (P = 0.005) and hMLH1 (P = 0.03) in the serum.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, 30-32 Ngan Sing Street, Shatin, Hong Kong. wkleung@cuhk.edu.hk

ABSTRACT
While there is no reliable serum biomarker for the diagnosis and monitoring of patients with gastric cancer, we tested the potential diagnostic and prognostic values of detecting methylation changes in the serum of gastric cancer patients. DNA was extracted from the pretherapeutic serum of 60 patients with confirmed gastric adenocarcinoma and 22 age-matched noncancer controls. Promoter hypermethylation in 10 tumour-related genes (APC, E-cadherin, GSTP1, hMLH1, MGMT, p15, p16, SOCS1, TIMP3 and TGF-beta RII) was determined by quantitative methylation-specific PCR (MethyLight). Preferential methylation in the serum DNA of gastric cancer patients was noted in APC (17%), E-cadherin (13%), hMLH1 (41%) and TIMP3 (17%) genes. Moreover, patients with stages III/IV diseases tended to have higher concentrations of methylated APC (P = 0.08), TIMP3 (P = 0.005) and hMLH1 (P = 0.03) in the serum. In all, 33 cancers (55%) had methylation detected in the serum in at least one of these four markers, while three normal subjects had methylation detected in the serum (specificity 86%). The combined use of APC and E-cadherin methylation markers identified a subgroup of cancer patients with worse prognosis (median survival 3.3 vs 16.1 months, P = 0.006). These results suggest that the detection of DNA methylation in the serum may carry both diagnostic and therapeutic values in gastric cancer patients.

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Kaplan–Meier analysis of the probability of overall survival in gastric cancer patients according to methylation status. (A) APC (P=0.20); (B) E-cadherin (P=0.09); (C) combined APC and E-cadherin (P=0.006).
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fig4: Kaplan–Meier analysis of the probability of overall survival in gastric cancer patients according to methylation status. (A) APC (P=0.20); (B) E-cadherin (P=0.09); (C) combined APC and E-cadherin (P=0.006).

Mentions: Apart from determining its diagnostic accuracy, we examined the potential prognostic value of detecting DNA methylation in the pretherapeutic serum of gastric cancer patients. Patients with methylated APC DNA in serum tended to have a nonsignificant shorter survival than patients with unmethylated APC. The difference appeared to be more marked in the initial 18 months of diagnosis. The overall median survival of patients with and without methylated APC in serum was 5.5 and 16.1 months, respectively (P=0.20, Figure 4A). Conversely, those with methylated E-cadherin tended to have a longer survival than patients with unmethylated gene (median survival 32.1 vs 14.1 months, P=0.09, Figure 4B). The presence of methylated hMLH1 and TIMP3 DNA in the serum was not associated with overall patients' survival (P=0.40 and 0.58, respectively).


Potential diagnostic and prognostic values of detecting promoter hypermethylation in the serum of patients with gastric cancer.

Leung WK, To KF, Chu ES, Chan MW, Bai AH, Ng EK, Chan FK, Sung JJ - Br. J. Cancer (2005)

Kaplan–Meier analysis of the probability of overall survival in gastric cancer patients according to methylation status. (A) APC (P=0.20); (B) E-cadherin (P=0.09); (C) combined APC and E-cadherin (P=0.006).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361805&req=5

fig4: Kaplan–Meier analysis of the probability of overall survival in gastric cancer patients according to methylation status. (A) APC (P=0.20); (B) E-cadherin (P=0.09); (C) combined APC and E-cadherin (P=0.006).
Mentions: Apart from determining its diagnostic accuracy, we examined the potential prognostic value of detecting DNA methylation in the pretherapeutic serum of gastric cancer patients. Patients with methylated APC DNA in serum tended to have a nonsignificant shorter survival than patients with unmethylated APC. The difference appeared to be more marked in the initial 18 months of diagnosis. The overall median survival of patients with and without methylated APC in serum was 5.5 and 16.1 months, respectively (P=0.20, Figure 4A). Conversely, those with methylated E-cadherin tended to have a longer survival than patients with unmethylated gene (median survival 32.1 vs 14.1 months, P=0.09, Figure 4B). The presence of methylated hMLH1 and TIMP3 DNA in the serum was not associated with overall patients' survival (P=0.40 and 0.58, respectively).

Bottom Line: DNA was extracted from the pretherapeutic serum of 60 patients with confirmed gastric adenocarcinoma and 22 age-matched noncancer controls.Promoter hypermethylation in 10 tumour-related genes (APC, E-cadherin, GSTP1, hMLH1, MGMT, p15, p16, SOCS1, TIMP3 and TGF-beta RII) was determined by quantitative methylation-specific PCR (MethyLight).Moreover, patients with stages III/IV diseases tended to have higher concentrations of methylated APC (P = 0.08), TIMP3 (P = 0.005) and hMLH1 (P = 0.03) in the serum.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, 30-32 Ngan Sing Street, Shatin, Hong Kong. wkleung@cuhk.edu.hk

ABSTRACT
While there is no reliable serum biomarker for the diagnosis and monitoring of patients with gastric cancer, we tested the potential diagnostic and prognostic values of detecting methylation changes in the serum of gastric cancer patients. DNA was extracted from the pretherapeutic serum of 60 patients with confirmed gastric adenocarcinoma and 22 age-matched noncancer controls. Promoter hypermethylation in 10 tumour-related genes (APC, E-cadherin, GSTP1, hMLH1, MGMT, p15, p16, SOCS1, TIMP3 and TGF-beta RII) was determined by quantitative methylation-specific PCR (MethyLight). Preferential methylation in the serum DNA of gastric cancer patients was noted in APC (17%), E-cadherin (13%), hMLH1 (41%) and TIMP3 (17%) genes. Moreover, patients with stages III/IV diseases tended to have higher concentrations of methylated APC (P = 0.08), TIMP3 (P = 0.005) and hMLH1 (P = 0.03) in the serum. In all, 33 cancers (55%) had methylation detected in the serum in at least one of these four markers, while three normal subjects had methylation detected in the serum (specificity 86%). The combined use of APC and E-cadherin methylation markers identified a subgroup of cancer patients with worse prognosis (median survival 3.3 vs 16.1 months, P = 0.006). These results suggest that the detection of DNA methylation in the serum may carry both diagnostic and therapeutic values in gastric cancer patients.

Show MeSH
Related in: MedlinePlus