R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
Exp Oncol. 2021 Dec;43(4):298-305. doi: 10.32471/exp-oncology.2312-8852.vol-43-no-4.17067.
Classification of breast cancer (BC) in the molecular subtypes had the enormous impact on the development of the individualized therapy. Nevertheless, there is a need for additional biomarkers that would help to refine molecular subtypes of BC and propose the therapeutic approach for each patient.
To study differential expression patterns of AIP, UCKL1, and PKN1 genes in blood sera and tumor tissue of patients with BC of different molecular subtypes.
The total extracellular RNA was isolated from serum of 26 BC patients. cDNAs was synthesized and quantitative polymerase chain reaction was performed. Also, immunohistochemical studies of UCKL, AIP and PKN1 were performed on deparaffined tissue sections. The study was supplemented by a bioinformatic analysis of the publicly available databases.
AIP and UCKL-1 extracellular mRNA levels were 100-1000-fold increased in blood sera of all BC patients, compared to the healthy donors. The highest levels were detected in the luminal A and HER2 (ERRB2) BC subtypes. The highest levels of PKN1 were detected blood sera of the patients with luminal B and basal subtypes; its expression levels were just 10-100-fold higher in BC samples compared to healthy donors.
The UCKL1, AIP, PKN1 genes are overexpressed at the mRNA level in blood sera of BC patients compared to the sera of healthy individuals. Among three genes under study, only for the AIP gene, the pattern of extracellular mRNA expression in sera paralleled to protein expression in BC tissues of each specified molecular subtype.
乳腺癌(BC)的分子亚型分类对个体化治疗的发展产生了巨大影响。然而,还需要额外的生物标志物来帮助细化 BC 的分子亚型,并为每位患者提出治疗方法。
研究 AIP、UCKL1 和 PKN1 基因在不同分子亚型 BC 患者血液血清和肿瘤组织中的差异表达模式。
从 26 名 BC 患者的血清中分离总细胞外 RNA。合成 cDNA 并进行定量聚合酶链反应。还对 UCKL、AIP 和 PKN1 进行了石蜡包埋组织切片的免疫组织化学研究。该研究还补充了对公共可用数据库的生物信息学分析。
与健康供体相比,所有 BC 患者的血液血清中 AIP 和 UCKL-1 细胞外 mRNA 水平增加了 100-1000 倍。在 luminal A 和 HER2(ERRB2)BC 亚型中检测到最高水平。在 luminal B 和基础亚型的患者血液血清中检测到最高水平的 PKN1;与健康供体相比,其表达水平仅高出 10-100 倍。
与健康个体的血清相比,BC 患者的血液血清中 UCKL1、AIP、PKN1 基因在 mRNA 水平上过度表达。在所研究的三个基因中,只有 AIP 基因,血清中细胞外 mRNA 表达模式与每个指定分子亚型的 BC 组织中的蛋白表达模式相平行。