关键词: Biomarker Breast cancer PALB2 Survival mRNA expression

Mesh : Female Humans Breast Neoplasms / genetics mortality pathology Disease-Free Survival East Asian People Fanconi Anemia Complementation Group N Protein / genetics Prognosis Real-Time Polymerase Chain Reaction

来  源:   DOI:10.1016/j.clbc.2023.03.003

Abstract:
PALB2 plays a crucial role in genome stability and the DNA repair process, and its mutation is associated with a moderate to high risk of breast cancer. However, the status and prognostic role of PALB2 expression in breast cancer are still unclear.
The expression level of PALB2 mRNA was evaluated by using quantitative real-time polymerase chain reaction in core biopsy samples from 563 primary breast cancer tissues.
In the entire cohort, low expression of PALB2 mRNA was significantly associated with poor survival (low vs. intermediate: DFS, adjusted HR = 1.79, 95% CI = 1.21-2.65, P = .003; DDFS, adjusted HR = 2.07, 95% CI = 1.34-3.20, P = .001; DSS, adjusted HR = 2.59, 95% CI = 1.45-4.64, P = .001; OS, adjusted HR = 2.77, 95% CI = 1.56-4.92, P = .001; low vs. high: DFS, adjusted HR = 1.57, 95% CI = 1.06-2.35, P = .026; DDFS, adjusted HR = 1.66, 95% CI = 1.08-2.55, P = .020; DSS, adjusted HR = 1.74, 95% CI = 1.00-3.03, P = .048; OS, adjusted HR = 1.59, 95% CI = 0.95-2.67, P = .08). Notably, among hormone receptor (HR)-positive/HER2-negative subtype, patients with low PALB2 expression also had significantly worse outcomes (low vs. intermediate: DFS, adjusted HR = 2.33, 95% CI = 1.32-4.13, P = .004; DDFS, adjusted HR = 2.78, 95% CI = 1.47-5.27, P < .001; DSS, adjusted HR = 3.08, 95% CI = 1.27-7.43, P = .013; OS, adjusted HR = 3.15, 95% CI = 1.32-7.50, P = .010; low vs. high: DFS, adjusted HR = 1.84, 95% CI = 1.04-3.28, P = .04; DDFS, adjusted HR = 1.82, 95% CI = 0.99-3.36, P = .05; DSS, adjusted HR = 2.06, 95% CI = 0.87-4.86, P = .10; OS, adjusted HR = 1.54, 95% CI = 0.71-3.33, P = .28).
Breast cancer patients with low expression of mRNA have a poor survival, suggesting that patients with PALB2 low expression may be the potential beneficiaries for PARP inhibitors therapy.
摘要:
背景:PALB2在基因组稳定性和DNA修复过程中起着至关重要的作用,其突变与乳腺癌的中度到高度风险有关。然而,PALB2在乳腺癌中的表达状况和预后作用尚不清楚.
方法:使用定量实时聚合酶链反应评估563例原发性乳腺癌组织的核心活检样本中PALB2mRNA的表达水平。
结果:在整个队列中,PALB2mRNA的低表达与低生存率显着相关(低与中间:DFS,调整后的HR=1.79,95%CI=1.21-2.65,P=0.003;DDFS,调整后的HR=2.07,95%CI=1.34-3.20,P=.001;DSS,调整后的HR=2.59,95%CI=1.45-4.64,P=.001;OS,调整后的HR=2.77,95%CI=1.56-4.92,P=.001;低与高:DFS,调整后的HR=1.57,95%CI=1.06-2.35,P=0.026;DDFS,调整后的HR=1.66,95%CI=1.08-2.55,P=0.020;DSS,调整后的HR=1.74,95%CI=1.00-3.03,P=0.048;OS,调整后的HR=1.59,95%CI=0.95-2.67,P=.08)。值得注意的是,在激素受体(HR)阳性/HER2阴性亚型中,PALB2低表达患者的预后也明显较差(低与中间:DFS,调整后的HR=2.33,95%CI=1.32-4.13,P=.004;DDFS,调整后的HR=2.78,95%CI=1.47-5.27,P<.001;DSS,调整后的HR=3.08,95%CI=1.27-7.43,P=0.013;OS,调整后的HR=3.15,95%CI=1.32-7.50,P=.010;低与高:DFS,调整后的HR=1.84,95%CI=1.04-3.28,P=.04;DDFS,调整后的HR=1.82,95%CI=0.99-3.36,P=0.05;DSS,调整后的HR=2.06,95%CI=0.87-4.86,P=.10;OS,调整后的HR=1.54,95%CI=0.71-3.33,P=.28)。
结论:mRNA低表达的乳腺癌患者生存期较差,提示PALB2低表达患者可能是PARP抑制剂治疗的潜在受益者.
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