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LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis.

Shigaki H, Baba Y, Watanabe M, Murata A, Iwagami S, Miyake K, Ishimoto T, Iwatsuki M, Baba H - Gastric Cancer (2012)

Bottom Line: Tumoral LINE-1 methylation range was 11.6-97.5 on a 0-100 scale (n = 203; mean 71.4, median 74.4, standard deviation 12.9).LINE-1 hypomethylation was significantly associated with shorter overall survival [log-rank p = 0.029; univariate HR 2.01, 95 % confidence interval (CI) 1.09-3.99, p = 0.023; stage-matched HR 1.88, 95 % CI 1.02-3.74, p = 0.041; multivariate HR 1.98, 95 % CI 1.04-4.04, p = 0.036].No significant effect modification was observed by any of the covariates in survival analysis (all p interaction >0.25).

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, Kumamoto, 860-8556, Japan.

ABSTRACT

Background: Genome-wide DNA hypomethylation plays an important role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level. In some types of human neoplasms, LINE-1 methylation level is attracting interest as a predictive marker for patient prognosis. However, the prognostic significance of LINE-1 hypomethylation in gastric cancer remains unclear.

Methods: Using 203 resected gastric cancer specimens, we quantified LINE-1 methylation using bisulfite-pyrosequencing technology. A Cox proportional hazards model was used to calculate the hazard ratio (HR), adjusted for the clinical and pathological variables.

Results: Gastric cancers showed significantly lower LINE-1 methylation levels compared to matched normal gastric mucosa (p < 0.0001; n = 74). Tumoral LINE-1 methylation range was 11.6-97.5 on a 0-100 scale (n = 203; mean 71.4, median 74.4, standard deviation 12.9). LINE-1 hypomethylation was significantly associated with shorter overall survival [log-rank p = 0.029; univariate HR 2.01, 95 % confidence interval (CI) 1.09-3.99, p = 0.023; stage-matched HR 1.88, 95 % CI 1.02-3.74, p = 0.041; multivariate HR 1.98, 95 % CI 1.04-4.04, p = 0.036]. No significant effect modification was observed by any of the covariates in survival analysis (all p interaction >0.25).

Conclusions: LINE-1 hypomethylation in gastric cancer is associated with shorter survival, suggesting that it has potential for use as a prognostic biomarker.

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Related in: MedlinePlus

Analysis with LINE-1 methylation as a continuous variable showed no significant relationship between LINE-1 methylation level and tumor stage (p = 0.64)
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Fig3: Analysis with LINE-1 methylation as a continuous variable showed no significant relationship between LINE-1 methylation level and tumor stage (p = 0.64)

Mentions: Next, we quantified the LINE-1 methylation in 206 cancer specimens and obtained valid results in 203 (99 %) of cases. LINE-1 methylation levels in the 203 cancers (Fig. 2b) were approximately normally distributed: mean 71.4, median 74.4, SD 12.9, range 11.6–97.5; inter-tertile range 70.0–77.4 (all in 0–100 scale). The LINE-1 methylation level was then divided into tertiles [Ter1 (77.4–97.5, n = 68), Ter2 (70.1–77.3, n = 66), Ter3 (11.6–70.0, n = 69)] for further analyses. We found that the LINE-1 methylation level was associated with tumor stage (p = 0.039; Table 1). However, in the analysis with LINE-1 methylation as a continuous variable, there was no significant relationship between LINE-1 methylation level and tumor stage (p = 0.64, Fig. 3). LINE-1 methylation was not significantly associated with other clinical or pathological variables.Table 1


LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis.

Shigaki H, Baba Y, Watanabe M, Murata A, Iwagami S, Miyake K, Ishimoto T, Iwatsuki M, Baba H - Gastric Cancer (2012)

Analysis with LINE-1 methylation as a continuous variable showed no significant relationship between LINE-1 methylation level and tumor stage (p = 0.64)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824342&req=5

Fig3: Analysis with LINE-1 methylation as a continuous variable showed no significant relationship between LINE-1 methylation level and tumor stage (p = 0.64)
Mentions: Next, we quantified the LINE-1 methylation in 206 cancer specimens and obtained valid results in 203 (99 %) of cases. LINE-1 methylation levels in the 203 cancers (Fig. 2b) were approximately normally distributed: mean 71.4, median 74.4, SD 12.9, range 11.6–97.5; inter-tertile range 70.0–77.4 (all in 0–100 scale). The LINE-1 methylation level was then divided into tertiles [Ter1 (77.4–97.5, n = 68), Ter2 (70.1–77.3, n = 66), Ter3 (11.6–70.0, n = 69)] for further analyses. We found that the LINE-1 methylation level was associated with tumor stage (p = 0.039; Table 1). However, in the analysis with LINE-1 methylation as a continuous variable, there was no significant relationship between LINE-1 methylation level and tumor stage (p = 0.64, Fig. 3). LINE-1 methylation was not significantly associated with other clinical or pathological variables.Table 1

Bottom Line: Tumoral LINE-1 methylation range was 11.6-97.5 on a 0-100 scale (n = 203; mean 71.4, median 74.4, standard deviation 12.9).LINE-1 hypomethylation was significantly associated with shorter overall survival [log-rank p = 0.029; univariate HR 2.01, 95 % confidence interval (CI) 1.09-3.99, p = 0.023; stage-matched HR 1.88, 95 % CI 1.02-3.74, p = 0.041; multivariate HR 1.98, 95 % CI 1.04-4.04, p = 0.036].No significant effect modification was observed by any of the covariates in survival analysis (all p interaction >0.25).

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, Kumamoto, 860-8556, Japan.

ABSTRACT

Background: Genome-wide DNA hypomethylation plays an important role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level. In some types of human neoplasms, LINE-1 methylation level is attracting interest as a predictive marker for patient prognosis. However, the prognostic significance of LINE-1 hypomethylation in gastric cancer remains unclear.

Methods: Using 203 resected gastric cancer specimens, we quantified LINE-1 methylation using bisulfite-pyrosequencing technology. A Cox proportional hazards model was used to calculate the hazard ratio (HR), adjusted for the clinical and pathological variables.

Results: Gastric cancers showed significantly lower LINE-1 methylation levels compared to matched normal gastric mucosa (p < 0.0001; n = 74). Tumoral LINE-1 methylation range was 11.6-97.5 on a 0-100 scale (n = 203; mean 71.4, median 74.4, standard deviation 12.9). LINE-1 hypomethylation was significantly associated with shorter overall survival [log-rank p = 0.029; univariate HR 2.01, 95 % confidence interval (CI) 1.09-3.99, p = 0.023; stage-matched HR 1.88, 95 % CI 1.02-3.74, p = 0.041; multivariate HR 1.98, 95 % CI 1.04-4.04, p = 0.036]. No significant effect modification was observed by any of the covariates in survival analysis (all p interaction >0.25).

Conclusions: LINE-1 hypomethylation in gastric cancer is associated with shorter survival, suggesting that it has potential for use as a prognostic biomarker.

Show MeSH
Related in: MedlinePlus