首页|上皮性卵巢癌化疗耐药组织中PARP1与铁死亡的相关性及临床意义

上皮性卵巢癌化疗耐药组织中PARP1与铁死亡的相关性及临床意义

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目的 研究上皮性卵巢癌化疗耐药组织中聚腺苷二磷酸核糖聚合酶 1(PARP1)与铁死亡的相关性及临床意义.方法 选择 2019 年 2 月至 2023 年 2 月期间在安徽省阜阳市颍上县人民医院经病理诊断为上皮性卵巢癌的 80 例患者,接受铂类为基础的化疗≥4 次并根据化疗效果分为化疗敏感组(n=31)和化疗耐药组(n=49).采用免疫组化检测化疗前上皮性卵巢癌组织中PARP1 的蛋白表达,采用荧光定量PCR检测化疗前上皮性卵巢癌组织中PARP1 及铁死亡标志基因GPX4、SLC7A11、TfR1的mRNA表达,比较两组间PARP1、GPX4、SLC7A11、TfR1表达水平的差异.随访患者的无进展生存期(PFS)和总生存期(OS).结果 化疗前FIGO分期Ⅲ~Ⅳ期、CA125≥35 U/mL的上皮性卵巢癌组织中PARP1 的高表达率高于FIGO分期Ⅰ~Ⅱ期、CA125<35 U/mL的上皮性卵巢癌组织,差异有统计学意义(χ2=4.129、9.095,P<0.05);上皮性卵巢癌化疗耐药组织中PARP1、GPX4、SLC7A11 的mRNA相对表达水平及PARP1 蛋白高表达率均高于上皮性卵巢癌化疗敏感组织,TfR1的mRNA相对表达水平低于上皮性卵巢癌化疗敏感组织,差异有统计学意义(t=23.487、20.030、23.378、22.752,χ2=5.905,P<0.05);上皮性卵巢癌中 PARP1 的 mRNA 相对表达水平与 GPX4、SLC7A11 的mRNA相对表达水平呈正相关(r=0.351、0.394),与TfR1的mRNA相对表达水平呈负相关(r=-0.364);与上皮性卵巢癌中PARP1 低表达患者比较,上皮性卵巢癌中PARP1 高表达患者的OS和PFS缩短,差异有统计学意义(χ2=4.851、5.623,P<0.05).结论 PARP1 高表达与上皮性卵巢癌化疗耐药、铁死亡减弱、生存预后不良相关.
Correlation and clinical significance of PARP1 and ferroptosis in chemotherapy-resistant epithelial ovarian cancer tissues
Objective To investigate the correlation between poly-ADP-ribose polymerase 1(PARP1)and ferroptosis in chemotherapy resistant epithelial ovarian cancer and its clinical significance.Meth-ods A total of 80 patients with epithelial ovarian cancer at Yingshang County People's Hospital in Fuyang City,Anhui Province,from February 2019 to February 2023 were selected for this study.These patients had received platinum-based chemotherapy at least 4 times and were divided into two groups:chemotherapy sensi-tive(n=31)and chemotherapy resistant(n=49)based on their response to treatment.Immunohistochemistry was used to detect the protein expression of PARP1 in epithelial ovarian cancer tissues before chemotherapy.Additionally,fluorescence quantitative PCR was used to measure the mRNA expression of PARP1 and ferrop-tosis marker genes GPX4,SLC7A11 and TfR11 in epithelial ovarian cancer tissues.The levels of PARP1,GPX4,SLC7A11 and TfR1 expression between the two groups were compared.Patients were followed up to assess their progression-free survival(PFS)and overall survival(OS).Results The high expression rate of PARP1 in epithelial ovarian cancer tissues with FIGO stageⅢ~Ⅳand CA125≥35 U/mL was higher than that of epithelial ovarian cancer tissues with FIGO stage Ⅰ~Ⅱand CA125<35 U/mL.The difference was statisti-cally significant(χ2=4.129,9.095,P<0.05).The relative mRNA expression levels of PARP1,GPX4 and SLC7A11 as well as the high expression rate of PARP1 were higher in chemotherapy resistant tissues compared to chemotherapy sensitive tissues.Conversely,the relative mRNA expression level of TfR1 was lower in che-motherapy resistant tissues than in chemotherapy sensitive tissues.The difference was statistically significant(t=23.487,20.030,23.378,22.752,χ2=5.905,P<0.05).The mRNA relative expression level of PARP1 in epi-thelial ovarian cancer was positively correlated with the mRNA relative expression levels of GPX4 and SLC7A11(correlation coefficient 0.351 and 0.394,respectively),and negatively correlated with the mRNA rel-ative expression level of TfR1(correlation coefficient-0.364).Patients with high PARP1 expression in epitheli-al ovarian cancer had shorter OS and PFS compared to patients with low PARP1 expression.The difference was statistically significant(χ2=4.851,5.623,P<0.05).Conclusion The high expression of PARP1 is correlated with chemotherapy resistance,reduced ferroptosis and poor survival prognosis in epithelial ovarian cancer.

Epithelial ovarian cancerChemotherapy resistancePARP1Ferroptosis

罗锐、王利侠、江汝伟

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安徽省阜阳市颍上县人民医院肿瘤内科,安徽,阜阳 236200

上皮性卵巢癌 化疗耐药 PARP1 铁死亡

蚌埠医学院自然科学研究重点项目

BYKY2019099ZD

2024

分子诊断与治疗杂志
中山大学

分子诊断与治疗杂志

CSTPCD
影响因子:0.65
ISSN:1674-6929
年,卷(期):2024.16(1)
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