Hao Junmei, Zhang Wenfeng, Lyu Yan, Zou Jiarui, Zhang Yunyun, Lyu Jiahong, Zhang Jianbo, Xie Shuishan, Zhang Cuiping, Zhang Jiandi, Tang Fangrong
Department of Pathology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China.
Yantai Quanticision Diagnostics, Inc., Yantai, China.
Front Oncol. 2021 Nov 9;11:737794. doi: 10.3389/fonc.2021.737794. eCollection 2021.
Ki67 is a biomarker of proliferation to be used in immunohistochemistry (IHC)-based surrogate assay to determine the necessity of cytotoxic therapy for Luminal-like breast cancer patients. cyclinD1 is another frequently used biomarker of proliferation. A retrospective study was performed here to investigate if these two biomarkers may be combined to improve the prognosis of Luminal-like patients.
Both Ki67 and cyclinD1 protein levels were measured absolutely and quantitatively using Quantitative Dot Blot method in 143 Luminal-like specimens. Optimized cutoffs for these two biomarkers were developed to evaluate their prognostic roles using Kaplan-Meier overall survival (OS) analysis.
cyclinD1 was found as an independent prognostic factor from Ki67 in univariate and multivariate OS analyses. At optimized cutoffs (cyclinD1 at 0.44 μmol/g and Ki67 at 2.31 nmol/g), the subgroup with both biomarkers below the cutoffs ( = 65) had 10-year survival probability at 90% in comparison to those with both biomarkers above the cutoffs ( = 18) with 8-year survival probability at 26% (log-rank test, 0.0001). This finding was used to modify the surrogate assay using IHC-based cyclinD1 scores, with -value decreased from 0.031 to 0.00061 or from 0.1 to 0.02, when the Ki67 score of 14 or 20% was used as cutoff, respectively, in the surrogate assay.
The current study supports the prospective investigation of cyclinD1 relevance in the clinic.
Ki67是一种增殖生物标志物,用于基于免疫组织化学(IHC)的替代检测,以确定管腔样乳腺癌患者进行细胞毒性治疗的必要性。细胞周期蛋白D1是另一种常用的增殖生物标志物。本研究进行了一项回顾性研究,以调查这两种生物标志物是否可以联合使用以改善管腔样患者的预后。
使用定量点杂交法在143例管腔样标本中绝对定量地测量Ki67和细胞周期蛋白D1的蛋白水平。通过Kaplan-Meier总生存(OS)分析确定这两种生物标志物的最佳临界值,以评估它们的预后作用。
在单变量和多变量OS分析中,细胞周期蛋白D1被发现是与Ki67独立的预后因素。在最佳临界值(细胞周期蛋白D1为0.44 μmol/g,Ki67为2.31 nmol/g)下,两种生物标志物均低于临界值的亚组(n = 65)10年生存概率为90%,而两种生物标志物均高于临界值的亚组(n = 18)8年生存概率为26%(对数秩检验,P = 0.0001)。这一发现被用于改进基于IHC的细胞周期蛋白D1评分的替代检测,当在替代检测中分别使用14%或20%的Ki67评分作为临界值时,P值从0.031降至0.00061或从0.1降至0.02。
本研究支持对细胞周期蛋白D1在临床中的相关性进行前瞻性研究。