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波多黎各裔西班牙裔/拉丁裔转移性去势抵抗性前列腺癌患者的DNA修复能力与临床病理特征

DNA Repair Capacity and Clinicopathological Characteristics in Puerto Rican Hispanic/Latino Patients with Metastatic Castration-Resistant Prostate Cancer.

作者信息

Matta Jaime, Ortiz-Sánchez Carmen, Encarnación-Medina Jarline, Torres-Caraballo Stephanie, Oliveras Jose, Park Jong, Arroyo Monica M, Ruiz-Deya Gilberto

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). 2025 Jan 16;17(2):279. doi: 10.3390/cancers17020279.

Abstract

BACKGROUND

Prostate cancer (PCa) accounts for 22% of the new cases diagnosed in Hispanic/Latino (H/L) men in the US. PCa has the highest incidence (38.3%) and mortality (16.4%) among all types of cancer diagnosed in Puerto Rico. We previously showed that PCa patients ( = 41) have a significant reduction of 59% in their levels of DNA repair capacity (DRC) when compared to controls ( = 14). This study aimed to evaluate DRC levels through the nucleotide excision repair (NER) pathway for the first time in 16 Puerto Rican H/L men with metastatic castration-resistant PCa (mCRPCa) while establishing comparisons with controls and PCa patients with indolent and aggressive disease.

METHODS

Blood samples and clinicopathological data from PCa cases ( = 71) and controls ( = 25) were evaluated. PCa cases were stratified into mCRPCa ( = 16), aggressive ( = 31), and indolent ( = 24). DRC levels through NER were measured in lymphocytes with the CometChip assay. The stratification by Gleason score (GS) was GS6 ( = 7), GS7 ( = 23), GS ≥ 8 ( = 20), and mCRPCa patients ( = 16).

RESULTS

Significant statistical differences were found when comparing the DRC values of the controls with any other of the four PCa patient groups. mCRPCa patients had the lowest mean DRC level of all four patient groups studied. The mean DRC level of mCRPCa patients was 6.65%, and compared to the controls, this represented a statistically significant reduction of 62% ( < 0.0001). Further analysis was performed to evaluate the contributions of age, anthropometric measurements, and prostate-specific antigen (PSA) levels to the DRC. Kaplan-Meier curves of mCRPCa revealed that survival probability decreased by approximately 50% by 30 months. This pilot study uses a blood-based phenotypic assay to present the first report of mCRPCa in Puerto Rican men and at a global level of DRC levels of mCRPCa patients.

CONCLUSIONS

This study evaluated DRC levels through the NER pathway for the first time in 16 Puerto Rican H/L men with mCRPCa. Significant differences in DRC values were found between the controls and the three PCa patient groups. Kaplan-Meier curves revealed that survival probability decreased by approximately 50% by 30 months, and only 20% of the cohort was alive at 50 months, confirming the lethality of mCRPCa in this H/L population. This pilot study represents the first report of metastatic PCa in Puerto Rican men at a global level of DRC levels of mCRPCa patients using a blood-based phenotypic assay.

摘要

背景

前列腺癌(PCa)占美国西班牙裔/拉丁裔(H/L)男性新诊断病例的22%。在波多黎各诊断出的所有类型癌症中,PCa的发病率(38.3%)和死亡率(16.4%)最高。我们之前表明,与对照组(n = 14)相比,PCa患者(n = 41)的DNA修复能力(DRC)水平显著降低了59%。本研究旨在首次通过核苷酸切除修复(NER)途径评估16名患有转移性去势抵抗性PCa(mCRPCa)的波多黎各H/L男性的DRC水平,同时与对照组以及患有惰性和侵袭性疾病的PCa患者进行比较。

方法

评估了PCa病例(n = 71)和对照组(n = 25)的血液样本和临床病理数据。PCa病例被分为mCRPCa(n = 16)、侵袭性(n = 31)和惰性(n = 24)。通过彗星芯片试验在淋巴细胞中测量通过NER的DRC水平。按 Gleason评分(GS)分层为GS6(n = 7)、GS7(n = 23)、GS≥8(n = 20)和mCRPCa患者(n = 16)。

结果

将对照组的DRC值与其他四个PCa患者组中的任何一组进行比较时,发现了显著的统计学差异。mCRPCa患者在所有四个研究的患者组中平均DRC水平最低。mCRPCa患者的平均DRC水平为6.65%,与对照组相比,这在统计学上显著降低了62%(P < 0.0001)。进行了进一步分析以评估年龄、人体测量指标和前列腺特异性抗原(PSA)水平对DRC的影响。mCRPCa的Kaplan-Meier曲线显示,到30个月时生存概率下降了约50%。这项初步研究使用基于血液的表型分析方法,首次报告了波多黎各男性中的mCRPCa以及全球范围内mCRPCa患者的DRC水平。

结论

本研究首次通过NER途径评估了16名患有mCRPCa的波多黎各H/L男性的DRC水平。对照组与三个PCa患者组之间的DRC值存在显著差异。Kaplan-Meier曲线显示,到30个月时生存概率下降了约50%,并且在50个月时该队列中只有20%的人存活,证实了mCRPCa在这个H/L人群中的致死性。这项初步研究代表了在全球范围内使用基于血液的表型分析方法对波多黎各男性转移性PCa患者的DRC水平的首次报告。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0603/11763443/09e90e6d61dd/cancers-17-00279-g004.jpg

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