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The prognostic value of DNA damage level in peripheral blood lymphocytes of chemotherapy-naïve patients with germ cell cancer

机译:未接受过化疗的生殖细胞癌患者外周血淋巴细胞DNA损伤水平的预后价值

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摘要

Germ cell tumors (GCTs) are extraordinarily sensitive to cisplatin (CDDP)-based chemotherapy. DNA damage represents one of the most important factors contributing to toxic effects of CDDP-based chemotherapy. This study was aimed to evaluate the prognostic value of DNA damage level in peripheral blood lymphocytes (PBLs) from chemo-naïve GCT patients. PBLs isolated from 59 chemotherapy-naïve GCT patients were included into this prospective study. DNA damage levels in PBLs were evaluated by the Comet assay and scored as percentage tail DNA by the Metafer-MetaCyte analyzing software. The mean ± SEM (standard error of the mean) of endogenous DNA damage level was 5.25 ± 0.64. Patients with DNA damage levels lower than mean had significantly better progression free survival (hazard ratio [HR] = 0.19, 95% CI (0.04 – 0.96), P = 0.01) and overall survival (HR = 0.00, 95% CI (0.00 – 0.0), P < 0.001) compared to patients with DNA damage levels higher than mean. Moreover, there was significant correlation between the DNA damage level and presence of mediastinal lymph nodes metastases, IGCCCG (International Germ Cell Cancer Collaborative Group) risk group, and serum tumor markers level. These data suggest that DNA damage levels in PBLs of GCT patients may serve as an important prognostic marker early identifying patients with poor outcome.
机译:生殖细胞肿瘤(GCT)对基于顺铂(CDDP)的化疗极为敏感。 DNA损伤代表导致基于CDDP的化学疗法的毒性作用的最重要因素之一。这项研究的目的是评估未经化学治疗的GCT患者外周血淋巴细胞(PBL)中DNA损伤水平的预后价值。从59名未接受过化疗的GCT患者中分离出的PBL被纳入这项前瞻性研究。通过彗星分析评估PBL中的DNA损伤水平,并通过Metafer-MetaCyte分析软件将其定为尾巴DNA百分比。内源性DNA损伤水平的平均值±SEM(平均值的标准误)为5.25±0.64。 DNA损伤水平低于平均水平的患者的无进展生存期(危险比[HR] = 0.19,95%CI(0.04 – 0.96),P = 0.01)和整体生存率(HR = 0.00,95%CI(0.00 – 0.0),P <0.001)与DNA损伤水平高于平均值的患者相比。此外,DNA损伤水平与纵隔淋巴结转移的存在,IGCCCG(国际生殖细胞癌协作组)风险组和血清肿瘤标志物水平之间存在显着相关性。这些数据表明,GCT患者的PBL中的DNA损伤水平可能是早期识别预后不良的重要预后标志物。

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