High Expression of p62 and ALDH1A3 Is Associated With Poor Prognosis in Luminal B Breast Cancer
High Expression of p62 and ALDH1A3 Is Associated With Poor Prognosis in Luminal B Breast Cancer
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DOI：
10.21873/anticanres.15818
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发表时间：
2022-07-01
影响因子：
2
通讯作者：
Akimoto, Kazunori
中科院分区：
文献类型：
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作者：
Ozaki, Ayaka;Motomura, Hitomi;Akimoto, Kazunori
背景/目的：p62（也称为隔离体1）参与癌症进展，并且p62的高表达表明在几种癌症类型中的不良临床结果。然而，乳腺癌亚型中p62基因表达与癌症干细胞（CSC）之间的关联仍不清楚。材料与方法：在本研究中，下载了原发性乳腺癌的基因组数据集（癌症基因组图谱，n=593;乳腺癌国际联盟的分子分类学，n= 2，509）。然后在来自相同患者的正常和乳腺癌组织中检测p62表达。Kaplan-Meier和多变量考克斯回归分析用于评估疾病特异性生存率。接下来，通过使用具有高活性的醛脱氢酶1（ALDH 1（高））的细胞来评估使用靶向小干扰RNA敲低p62对细胞活力和体外肿瘤球形成的影响。结果：正常样、管腔型A或管腔型B乳腺癌p62（高表达）患者预后差。此外，p62（高）ALDH 1A 3（高）管腔B型患者也表现出较差的预后。p62的敲低抑制了管腔B型细胞系BT-474和MDA-MB-361的ALDH 1（高）细胞的活力和肿瘤球形成。这些结果表明，p62对于ALDH 1阳性管腔型B乳腺CSC的癌性进展是必需的，并且有助于管腔型B乳腺癌的不良预后。结论：p62是ALDH 1阳性管腔型B乳腺CSC的潜在预后标志物和治疗靶点。
Background/Aim: p62 (also known as sequestosome 1) is involved in cancer progression, and high expression of p62 indicates poor clinical outcome in several cancer types. However, the association between p62 gene expression and cancer stem cells (CSCs) in breast cancer subtypes remains unclear. Materials and Methods: In the present study, genomic datasets of primary breast cancer (The Cancer Genome Atlas, n=593; and Molecular Taxonomy of Breast Cancer International Consortium, n=2,509) were downloaded. p62 Expression was then examined in normal and breast cancer tissues derived from the same patients. Kaplan-Meier and multivariate Cox regression analyses were employed to evaluate disease-specific survival. Next, the effect on cell viability and in vitro tumor-sphere formation of p62 knockdown using targeted small interfering RNA was assessed by using cells with high activity of aldehyde dehydrogenase 1 (ALDH1(high)). Results: Patients with normal-like, luminal A or luminal B breast cancer with p62(high) had poor prognosis. Furthermore, patients with p62(high) ALDH1A3(high) luminal B type also exhibited poor prognoses. Knockdown of p62 suppressed viability and tumor-sphere formation by ALDH1(high) cells of the luminal B-type cell lines BT-474 and MDA-MB-361. These results suggest that p62 is essential for cancerous progression of ALDH1-positive luminal B breast CSCs, and contributes to poor prognosis of luminal B breast cancer. Conclusion: p62 is potentially a prognostic marker and therapeutic target for ALDH1-positive luminal B breast CSCs.