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谷胱甘肽S-转移酶P1(GSTP1)和腺瘤性息肉病蛋白(APC)启动子基因的甲基化状态作为前列腺癌早期检测和肿瘤侵袭性的潜在生物标志物:来自摩洛哥队列的见解

Methylation status of GSTP1 and APC promoter genes as potential biomarkers for early detection and tumor aggressiveness in prostate cancer: insights from a Moroccan cohort.

作者信息

Mharrach Imane, Aqerrout Mouna, Tadlaoui Kaoutar Anouar, Laraqui Abdelilah, Ghazzaly Anouar El, Ennaji Moulay Mustapha

机构信息

Team of Virology, Oncology and Biotechnologies. Laboratory of Virology, Oncology, Biosciences, Environment and New Energies, Faculty of Sciences and Techniques - Mohammedia, University Hassan II of Casablanca, PO BOX 146, Casablanca, 20650, Morocco.

Royal School of Military Health Service, Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious, and Tropical Diseases, Mohammed V Military Teaching Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, 10000, Morocco.

出版信息

Mol Biol Rep. 2025 Jul 15;52(1):711. doi: 10.1007/s11033-025-10812-9.

DOI:10.1007/s11033-025-10812-9
PMID:40663294
Abstract

BACKGROUND

Prostate cancer (PCa) is one of the leading causes of morbidity and mortality among men worldwide. While age, race and family history are established risk factors, their molecular underpinning remain poorly understood. Aberrant promoter methylation is a well-known mechanism for silencing tumor suppressor genes in PCa. This study evaluates the methylation status of glutathione-S-transferase-P1 (GSTP1) and adenomatous polyposis coli (APC) genes in Moroccan men with PCa, assessing their potential as biomarkers for early detection and tumor characterization.

METHODS

A total of 70 prostate cancer tissue samples and 50 control tissues were analyzed. Methylation specific PCR (MSP) was used to evaluate the promoter methylation status of GSTP1 and APC, The results were correlated with age, PSA levels, Gleason score, tumor stage, and life style factors.

RESULTS

GSTP1 promoter methylation was observed in 79% of PCa cases and was significantly associated with lower Gleason scores (= 6: 64%, P = 0.006) and early T-stages tumors (T1 and T2, P = 0.002). APC methylation was found in 63% of cases and showed a significant association with higher Gleason scores (> 6: 59%, P = 0.007). Although APC methylation did not significantly correlate with pathological T-stage, it was more frequent in early stages (T1: 45%, T2: 34%). No significant associations were observed between GSTP1 or APC methylation and age, PSA levels, smoking, or alcohol consumption.

CONCLUSION

promoter methylation of GSTP1 and APC is frequent in Moroccan prostate cancer patients. GSTP1 methylation appears to be associated with early stage disease, Whereas APC methylation is linked to tumor aggressiveness. These findings suggest the potential utility of GSTP1 and APC promoter methylation as biomarkers for prostate cancer detection and characterization, further validation with larger cohorts and gene expression analysis is needed to confirm their clinical relevance.

摘要

背景

前列腺癌(PCa)是全球男性发病和死亡的主要原因之一。虽然年龄、种族和家族史是公认的风险因素,但其分子基础仍知之甚少。异常的启动子甲基化是前列腺癌中使肿瘤抑制基因沉默的一种众所周知的机制。本研究评估了摩洛哥前列腺癌男性患者中谷胱甘肽 - S - 转移酶 - P1(GSTP1)和腺瘤性息肉病基因(APC)的甲基化状态,评估它们作为早期检测和肿瘤特征生物标志物的潜力。

方法

共分析了70份前列腺癌组织样本和50份对照组织。采用甲基化特异性PCR(MSP)评估GSTP1和APC的启动子甲基化状态,结果与年龄、前列腺特异性抗原(PSA)水平、 Gleason评分、肿瘤分期和生活方式因素相关。

结果

79%的前列腺癌病例中观察到GSTP1启动子甲基化,且与较低的Gleason评分(≤6:64%,P = 0.006)和早期T分期肿瘤(T1和T2,P = 0.002)显著相关。63%的病例中发现APC甲基化,且与较高的Gleason评分(>6:59%,P = 0.007)显著相关。虽然APC甲基化与病理T分期无显著相关性,但在早期阶段(T1:45%,T2:34%)更常见。未观察到GSTP1或APC甲基化与年龄、PSA水平、吸烟或饮酒之间存在显著关联。

结论

GSTP1和APC的启动子甲基化在摩洛哥前列腺癌患者中很常见。GSTP1甲基化似乎与早期疾病相关,而APC甲基化与肿瘤侵袭性有关。这些发现表明GSTP1和APC启动子甲基化作为前列腺癌检测和特征生物标志物的潜在效用,需要更大规模的队列研究和基因表达分析进一步验证以确认其临床相关性。

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