Centro de Genética y Biología Molecular, Universidad de San Martín de Porres, Lima, Peru.
Facultad de Medicina Humana, Universidad de San Martín de Porres, Chiclayo, Peru.
Mol Genet Genomic Med. 2023 Dec;11(12):e2260. doi: 10.1002/mgg3.2260. Epub 2023 Aug 7.
Promoter hypermethylation is one of the enabling mechanisms of hallmarks of cancer. Tumor suppressor genes like RARB and GSTP1 have been reported as hypermethylated in breast cancer tumors compared with normal tissues in several populations. This case-control study aimed to determine the association between the promoter methylation ratio (PMR) of RARB and GSTP1 genes (separately and as a group) with breast cancer and its clinical-pathological variables in Peruvian patients, using a liquid biopsy approach.
A total of 58 breast cancer patients and 58 healthy controls, matched by age, participated in the study. We exacted cell-free DNA (cfDNA) from blood plasma and converted it by bisulfite salts. Methylight PCR was performed to obtain the PMR value of the studied genes. We determined the association between PMR and breast cancer, in addition to other clinicopathological variables. The sensitivity and specificity of the PMR of these genes were obtained.
A significant association was not found between breast cancer and the RARB PMR (OR = 1.90; 95% CI [0.62-6.18]; p = 0.210) or the GSTP1 PMR (OR = 6.57; 95% CI [0.75-307.66]; p = 0.114). The combination of the RARB + GSTP1 PMR was associated with breast cancer (OR = 2.81; 95% CI [1.02-8.22]; p = 0.026), controls under 50 years old (p = 0.048), patients older than 50 (p = 0.007), and postmenopausal (p = 0.034). The PMR of both genes showed a specificity of 86.21% and a sensitivity of 31.03%.
Promoter hypermethylation of RARB + GSTP1 genes is associated with breast cancer, older age, and postmenopausal Peruvian patients. The methylated promoter of the RARB + GSTP1 genes needs further validation to be used as a biomarker for liquid biopsy and as a recommendation criterion for additional tests in asymptomatic women younger than 50 years.
启动子超甲基化是癌症特征的一种实现机制。在多个人群中，与正常组织相比，RARB 和 GSTP1 等肿瘤抑制基因在乳腺癌肿瘤中被报告为超甲基化。本病例对照研究旨在使用液体活检方法，确定 RARB 和 GSTP1 基因（分别和作为一组）启动子甲基化比率（PMR）与秘鲁患者乳腺癌及其临床病理变量之间的关联。
共有 58 名乳腺癌患者和 58 名年龄匹配的健康对照者参加了这项研究。我们从血浆中提取无细胞 DNA（cfDNA）并用亚硫酸氢盐盐转化。进行 Methylight PCR 以获得研究基因的 PMR 值。我们确定了 PMR 与乳腺癌以及其他临床病理变量之间的关联。获得了这些基因的 PMR 的敏感性和特异性。
未发现乳腺癌与 RARB PMR（OR=1.90；95%CI [0.62-6.18]；p=0.210）或 GSTP1 PMR（OR=6.57；95%CI [0.75-307.66]；p=0.114）之间存在显著关联。RARB+GSTP1 PMR 的组合与乳腺癌（OR=2.81；95%CI [1.02-8.22]；p=0.026）、50 岁以下的对照组（p=0.048）、50 岁以上的患者（p=0.007）和绝经后（p=0.034）有关。这两个基因的 PMR 特异性为 86.21%，灵敏度为 31.03%。
RARB+GSTP1 基因的启动子超甲基化与秘鲁乳腺癌患者的年龄较大和绝经后状态相关。RARB+GSTP1 基因的甲基化启动子需要进一步验证，以作为液体活检的生物标志物，并作为建议标准，用于对 50 岁以下无症状女性进行额外检查。
