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Thomas Flaig, MD


Methylation of PENK: Potential Biomarker for Early Detection of Bladder Cancer?

By: Joshua D. Madera, MS
Posted: Wednesday, January 11, 2023

For patients with bladder carcinoma, methylation of the proenkephalin (PENK) gene may serve as a biomarker for early urine-based detection, according to a study published in BMC Cancer. However, additional investigative efforts are necessary to confirm its efficacy and accuracy in the noninvasive detection of bladder carcinoma, explained Jae Sung Lim, MD, of Chungnam National University College of Medicine, Daejeon, Korea, and colleagues.

A total of 169 urine sediments were collected for analysis from patients with bladder carcinoma (n = 55), benign urologic diseases (n = 25), other urologic cancers (n = 8), and healthy controls (n = 81). All samples were collected before any surgical intervention was completed. Samples subsequently underwent quantitative methylation-specific real-time polymerase chain reaction. Primary tumors from nine patients underwent CpG methylation microarray analysis, and methylation status was confirmed using bisulfite pyrosequencing.

The study findings revealed that the ability of the quantitative methylation-specific real-time polymerase chain reaction to detect Ta high-grade and advanced tumor stages (T1–T4) in patients with bladder carcinoma had an overall specificity of 92.5% and a sensitivity of 86.5%. In addition, sensitivities of 100%, 88.5%, 83.3%, and 55.6% were identified for T2 to T4, T1, Ta high-grade, and Ta low-grade tumors, respectively. Moreover, the methylation status of the PENK gene was positively associated with bladder carcinoma tumor grade. However, no significant association was revealed between the methylation status of the PENK gene and independent patient factors including sex, age, and tumor stage. No significant associations were identified for the SIM2 or DMC1 genes.

Disclosure: For full disclosures of the study authors, visit

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