Co-expression of PKCζ and ALDH1A3 Is Associated With Poor Chemotherapeutic Responses in Basal-like Breast Cancer.

IF 2.6 4区医学 Q2 GENETICS & HEREDITY

Cancer Genomics & Proteomics Pub Date : 2026-03-01 DOI:10.21873/cgp.20579

Yuka Nagashima, Megumi Ogino, Ranman Okiyama, Ryosuke Chiwaki, Hayato Ishii, Kana Nohata, Ayaka Nakahara, Ayaka Ozaki, Takahiro Kasai, Shoma Tamori, Shigeo Ohno, Kazunori Sasaki, Kazunori Akimoto

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引用次数: 0

Abstract

Background/aim: The association between the expression of protein kinase C zeta (PKCζ) and chemotherapeutic responses among different subtypes of breast cancer has yet to be fully elucidated. The present study aimed to investigate the association between PKCζ expression and disease-specific survival (DSS) rates, with a particular focus on the influence of chemotherapy and cancer stem cell (CSC)-associated ALDH1A3 expression.

Materials and methods: Clinical and gene expression data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (n=2,509) were analyzed using Kaplan-Meier and Cox proportional hazards models. The findings were validated using The Cancer Genome Atlas (TCGA) Pan-Cancer Atlas dataset (n=1,084).

Results: In the METABRIC dataset, high PKCζ expression (PKCζ ^high) was associated with poor DSS rates in patients with the normal-like, claudin-low and basal-like subtypes treated with chemotherapy. Consistent results were obtained in TCGA dataset, where PKCζ ^high expression in basal-like breast cancer predicted poor prognosis, especially among patients treated with cyclophosphamide, an alkylating agent. Combined analysis further revealed that patients with high expression of both PKCζ and ALDH1A3 (PKCζ ^high/ALDH1A3 ^high) basal-like tumors treated with cyclophosphamide, doxorubicin, or fluorouracil had the worst DSS rates compared with other groups. In addition, PKCζ ^high/ALDH1A3 ^high basal-like tumors treated with anthracycline- or taxane-based regimens also exhibited poorer prognoses compared with other groups.

Conclusion: PKCζ contributes to chemotherapeutic resistance, especially in patients with ALDH1A3-positive basal-like breast cancer, possibly through the regulation of CSC survival and proliferation. Moreover, PKCζ, either alone or in combination with ALDH1A3 expression, may serve as a prognostic biomarker for predicting the therapeutic efficacy of chemotherapy in basal-like breast cancer.

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PKCζ和ALDH1A3的共表达与基底样乳腺癌不良化疗反应相关

背景/目的：蛋白激酶Cζ (PKCζ)的表达与不同亚型乳腺癌化疗反应之间的关系尚未完全阐明。本研究旨在探讨PKCζ表达与疾病特异性生存（DSS）率之间的关系，特别关注化疗和癌症干细胞（CSC）相关的ALDH1A3表达的影响。材料和方法：采用Kaplan-Meier和Cox比例风险模型分析来自国际乳腺癌分子分类协会（METABRIC）数据集（n= 2509）的临床和基因表达数据。研究结果使用癌症基因组图谱（TCGA）泛癌症图谱数据集（n=1,084）进行验证。结果：在METABRIC数据集中，PKCζ高表达（PKCζ高）与接受化疗的正常样，低claudin和基底样亚型患者的低DSS率相关。在TCGA数据集中获得了一致的结果，PKCζ在基底样乳腺癌中的高表达预示着不良预后，特别是在接受烷基化剂环磷酰胺治疗的患者中。联合分析进一步发现，与其他组相比，使用环磷酰胺、阿霉素或氟尿嘧啶治疗的PKCζ和ALDH1A3 （PKCζ高/ALDH1A3高）基底样肿瘤患者的DSS率最差。此外，PKCζ高/ALDH1A3高基底样肿瘤用蒽环类或紫杉醇为基础的方案治疗也表现出较差的预后。结论：PKCζ参与化疗耐药，特别是在aldh1a3阳性基底样乳腺癌患者中，可能通过调节CSC的存活和增殖。此外，PKCζ，无论是单独表达还是与ALDH1A3联合表达，都可能作为预测基底样乳腺癌化疗疗效的预后生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Genomics & Proteomics ONCOLOGY-GENETICS & HEREDITY

CiteScore

5.00

自引率

8.00%

发文量

期刊介绍： Cancer Genomics & Proteomics (CGP) is an international peer-reviewed journal designed to publish rapidly high quality articles and reviews on the application of genomic and proteomic technology to basic, experimental and clinical cancer research. In this site you may find information concerning the editorial board, editorial policy, issue contents, subscriptions, submission of manuscripts and advertising. The first issue of CGP circulated in January 2004. Cancer Genomics & Proteomics is a journal of the International Institute of Anticancer Research. From January 2013 CGP is converted to an online-only open access journal. Cancer Genomics & Proteomics supports (a) the aims and the research projects of the INTERNATIONAL INSTITUTE OF ANTICANCER RESEARCH and (b) the organization of the INTERNATIONAL CONFERENCES OF ANTICANCER RESEARCH.