Hypermethylated SFRP1, but none of other nine genes "informative" for western countries, is valuable for bladder cancer detection in Mainland China.
OBJECTIVE
A 11-gene set by methylation-specific PCR in urine sediments for sensitive/specific detection of bladder cancer has been identified previously. In this study, we have evaluated 10 DNA methylation biomarkers that have been reported informative in western countries for bladder cancer diagnosis for a better set.


METHODS
The promoter CpG Islands of the following 10 genes: CDH1, FANCF, LOXL1, LOXL4, p16INK4, SFRP1, SOX9, TIG1, TIMP3, and XAF1 have been subjected to methylation-specific PCR analysis in the DNA of 2 bladder cancer cell lines, 2 normal bladder tissues and urine sediments of 82 bladder cancer patients, 15 non-cancerous urogenital patients and 5 healthy volunteers.


RESULTS
Both XAF1 and LOXL1 genes were heterozygously methylated in the normal bladder tissues, showing no cancer state specificity. While the hypermethylated states were detected in urine sediments of bladder cancer at a frequency not less than 2.4% (2/82 cases), nine genes were also methylated in the patients of the non-cancerous urogenital diseases. The methylated SFRP1 was detected in 36.6% (30/82 cases) of bladder cancer and 6.7% (1/15 cases) of non-cancerous urogenital diseases, showing the bladder cancer specificity.


CONCLUSIONS
Inclusion of the SFRP1 gene into a set of 11 genes has improved the bladder cancer detection. The insufficiency of predicting disease onset in this study with the previously recommended targets in western countries suggests a possible disease disparity between these two populations. Alternatively, the tissue-specific methylation might be mistaken as the cancer specific in the studies where no non-cancerous lesion controls were involved.
Sun
Jinfeng
J
School of Medicine, Fudan University, 200032 Shanghai, China.
Chen
Zhou
Z
Zhu
Tongyu
T
Yu
Jian
J
Ma
Kelong
K
Zhang
Hongyu
H
He
Yinghua
Y
Luo
Xiaoying
X
Zhu
Jingde
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000502:physiology; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics; D002681:China; D019175:DNA Methylation; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D011379:Prognosis; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics; D019366:Western World; D055815:Young Adult; D000094742:Secreted Frizzled-Related Proteins
D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins