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NF-κB 信号通路和 DNA 修复基因 PARP1 在预测乳腺癌手术后远处转移中的价值。

Value of the NF-κB signalling pathway and the DNA repair gene PARP1 in predicting distant metastasis after breast cancer surgery.

机构信息

School of Public Health, Southwest Medical University, 1 Xianglin Road, Luzhou, 646000, Sichuan, China.

Department of Pathology, The First Affiliated Hospital of Southwest Medical University, 25 Taiping Road, Luzhou, 646000, Sichuan, China.

出版信息

Sci Rep. 2024 Feb 22;14(1):4402. doi: 10.1038/s41598-023-49156-4.

DOI:10.1038/s41598-023-49156-4
PMID:38388665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10883999/
Abstract

The DNA repair gene PARP1 and NF-κB signalling pathway affect the metastasis of breast cancer by influencing the drug resistance of cancer cells. Therefore, this study focused on the value of the DNA repair gene PARP1 and NF-κB pathway proteins in predicting the postoperative metastasis of breast cancer. A nested case‒control study was performed. Immunohistochemical methods were used to detect the expression of these genes in patients. ROC curves were used to analyse the predictive effect of these factors on distant metastasis. The COX model was used to evaluate the effects of PARP1 and TNF-α on distant metastasis. The results showed that the expression levels of PARP1, IKKβ, p50, p65 and TNF-α were significantly increased in the metastasis group (P < 0.001). PARP1 was correlated with IKKβ, p50, p65 and TNF-α proteins (P < 0.001). There was a correlation between IKKβ, p50, p65 and TNF-α proteins (P < 0.001). ROC curve analysis showed that immunohistochemical scores for PARP1 of > 6, IKKβ of > 4, p65 of > 4, p50 of > 2, and TNF-α of > 4 had value in predicting distant metastasis (Se = 78.35%, Sp = 79.38%, AUC = 0.843; Se = 64.95%, Sp = 70.10%, AUC = 0.709; Se = 60.82%, Sp = 69.07%, AUC = 0.6884). Cox regression analysis showed that high expression levels of PARP1 and TNF-α were a risk factor for distant metastasis after breast cancer surgery (RR = 4.092, 95% CI 2.475-6.766, P < 0.001; RR = 1.825, 95% CI 1.189-2.799, P = 0.006). Taken together, PARP1 > 6, p50 > 2, and TNF-α > 4 have a certain value in predicting breast cancer metastasis, and the predictive value is better when they are combined for diagnosis (Se = 97.94%, Sp = 71.13%).

摘要

DNA 修复基因 PARP1 和 NF-κB 信号通路通过影响癌细胞的耐药性影响乳腺癌的转移。因此,本研究重点探讨 DNA 修复基因 PARP1 和 NF-κB 通路蛋白在预测乳腺癌术后转移中的价值。采用巢式病例对照研究。免疫组织化学方法检测患者基因表达。ROC 曲线分析这些因素对远处转移的预测效果。COX 模型评估 PARP1 和 TNF-α 对远处转移的影响。结果显示,转移组 PARP1、IKKβ、p50、p65 和 TNF-α 蛋白表达水平显著升高(P<0.001)。PARP1 与 IKKβ、p50、p65 和 TNF-α 蛋白呈正相关(P<0.001)。IKKβ、p50、p65 和 TNF-α 蛋白之间存在相关性(P<0.001)。ROC 曲线分析显示,PARP1 免疫组化评分>6、IKKβ>4、p65>4、p50>2、TNF-α>4 对预测远处转移有价值(Se=78.35%,Sp=79.38%,AUC=0.843;Se=64.95%,Sp=70.10%,AUC=0.709;Se=60.82%,Sp=69.07%,AUC=0.6884)。Cox 回归分析显示,PARP1 和 TNF-α 高表达是乳腺癌术后远处转移的危险因素(RR=4.092,95%CI 2.475-6.766,P<0.001;RR=1.825,95%CI 1.189-2.799,P=0.006)。综上所述,PARP1>6、p50>2、TNF-α>4 对预测乳腺癌转移有一定价值,联合诊断时预测价值更高(Se=97.94%,Sp=71.13%)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/87b340e3b3d0/41598_2023_49156_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/4e34481ab6ff/41598_2023_49156_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/3bf01c59b0c7/41598_2023_49156_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/742e83103c1c/41598_2023_49156_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/b5cdc96038cb/41598_2023_49156_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/ea1a26aae2be/41598_2023_49156_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/378e3f224049/41598_2023_49156_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/c484e951f3c2/41598_2023_49156_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/87b340e3b3d0/41598_2023_49156_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/4e34481ab6ff/41598_2023_49156_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/3bf01c59b0c7/41598_2023_49156_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/742e83103c1c/41598_2023_49156_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/b5cdc96038cb/41598_2023_49156_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/ea1a26aae2be/41598_2023_49156_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/378e3f224049/41598_2023_49156_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/c484e951f3c2/41598_2023_49156_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338b/10883999/87b340e3b3d0/41598_2023_49156_Fig8_HTML.jpg

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