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前列腺癌患者DNA修复能力降低:使用彗星芯片的表型研究方法

Reduced DNA Repair Capacity in Prostate Cancer Patients: A Phenotypic Approach Using the CometChip.

作者信息

Ortiz-Sánchez Carmen, Encarnación-Medina Jarline, Park Jong Y, Moreno Natasha, Ruiz-Deya Gilberto, Matta Jaime

机构信息

Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR 00716-2347, Puerto Rico.

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.

出版信息

Cancers (Basel). 2022 Jun 25;14(13):3117. doi: 10.3390/cancers14133117.

DOI:10.3390/cancers14133117
PMID:35804887
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9264934/
Abstract

Prostate cancer (PCa) accounts for 22% of the new cases diagnosed in Hispanic men in the US. Among Hispanics, Puerto Rican (PR) men show the highest PCa-specific mortality. Epidemiological studies using functional assays in lymphocytes have demonstrated that having low DRC is a significant risk factor for cancer development. The aim of this study was to evaluate variations in DRC in PR men with PCa. Lymphocytes were isolated from blood samples from PCa cases (n = 41) and controls (n = 14) recruited at a hospital setting. DRC levels through the nucleotide excision repair (NER) pathway were measured with the CometChip using UVC as a NER inductor. The mean DRC for controls and PCa cases were 20.66% (±7.96) and 8.41 (±4.88), respectively (p < 0.001). The relationship between DRC and tumor aggressiveness was also evaluated. Additional comparisons were performed to evaluate the contributions of age, anthropometric measurements, and prostate-specific antigen levels to the DRC. This is the first study to apply the CometChip in a clinical cancer study. Our results represent an innovative step in the development of a blood-based screening test for PCa based on DRC levels. Our data also suggest that DRC levels may have the potential to discriminate between aggressive and indolent cases.

摘要

前列腺癌(PCa)占美国西班牙裔男性新诊断病例的22%。在西班牙裔人群中,波多黎各(PR)男性的前列腺癌特异性死亡率最高。利用淋巴细胞功能测定的流行病学研究表明,DNA修复能力(DRC)低是癌症发生的一个重要危险因素。本研究的目的是评估患有前列腺癌的PR男性的DRC变化。从医院招募的前列腺癌病例(n = 41)和对照组(n = 14)的血液样本中分离淋巴细胞。使用CometChip以紫外线(UVC)作为核苷酸切除修复(NER)诱导剂来测量通过NER途径的DRC水平。对照组和前列腺癌病例组的平均DRC分别为20.66%(±7.96)和8.41(±4.88)(p < 0.001)。还评估了DRC与肿瘤侵袭性之间的关系。进行了额外的比较,以评估年龄、人体测量指标和前列腺特异性抗原水平对DRC的影响。这是第一项将CometChip应用于临床癌症研究的研究。我们的结果代表了基于DRC水平开发前列腺癌血液筛查试验的一个创新步骤。我们的数据还表明,DRC水平可能有潜力区分侵袭性和惰性病例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf5/9264934/fdb0904fac8d/cancers-14-03117-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf5/9264934/d165f2f8736a/cancers-14-03117-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf5/9264934/18bdde493f7c/cancers-14-03117-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf5/9264934/fdb0904fac8d/cancers-14-03117-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf5/9264934/d165f2f8736a/cancers-14-03117-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf5/9264934/18bdde493f7c/cancers-14-03117-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf5/9264934/fdb0904fac8d/cancers-14-03117-g003.jpg

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Targeting DNA Damage Response in Prostate and Breast Cancer.针对前列腺癌和乳腺癌中的DNA损伤反应
Int J Mol Sci. 2020 Nov 4;21(21):8273. doi: 10.3390/ijms21218273.
3
DNA Damage Repair Deficiency in Prostate Cancer.
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Mutat Res. 2023 Jan-Jun;826:111813. doi: 10.1016/j.mrfmmm.2022.111813. Epub 2022 Dec 31.
4
Novel In Vivo CometChip Reveals NDMA-Induced DNA Damage and Repair in Multiple Mouse Tissues.新型体内彗星芯片揭示了 NDMA 诱导的多种小鼠组织中的 DNA 损伤和修复。
Int J Mol Sci. 2022 Oct 4;23(19):11776. doi: 10.3390/ijms231911776.
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Trends Cancer. 2020 Nov;6(11):974-984. doi: 10.1016/j.trecan.2020.05.011. Epub 2020 Jun 6.
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