Fujino Shiori, Yamashita Keishi, Okamoto Riku, Shibaki Shumpei, Naito Kanako, Minoura Hiroyuki, Ikemura Kyonosuke, Kuroda Yu, Okuno Kota, Watanabe Akiko, Oki Keiko, Kidachi Mikiko, Nie Yusuke, Tokito Takaaki, Kikuchi Mariko, Kato Hiroshi, Naitoh Takeshi, Hiki Naoki, Kumamoto Yusuke, Sangai Takafumi
Division of Advanced Surgical Oncology, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Department of Breast and Thyroid Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
Ann Surg Oncol. 2025 Aug 5. doi: 10.1245/s10434-025-17944-z.
Breast cancer (BC) is a heterogeneous disease with variable prognosis, highlighting the need for novel biomarkers and therapeutic targets. This study investigates the role of the CDO1 gene, which encodes cysteine dioxygenase 1, in BC progression and its potential impact on patient outcomes.
We performed stable transfection of CDO1 in the MDA-MB231 triple negative BC (TNBC) cell line, followed by analysis of gene expression profiles using microarray technology.
CDO1 is significantly upregulated in transfected cells, leading to the induction of several tumor suppressor genes, including DEFB1, HOPX, and FRMD3. Correlation analysis in clinical BC samples revealed significant associations between CDO1 and other key genes, including SLC1A7 and KITLG, underscoring its relevance in tumor biology. Functional assays demonstrated that CDO1 expression is associated with increased apoptosis and reduced cell viability, suggesting a protective role against tumor progression. Additionally, we observed alterations in oncogenic pathways related to extracellular matrix and protease (SGRN and ADAMTS1), indicating that CDO1 may alleviate metastatic potential putatively via stromal reprogramming.
Our findings establish CDO1 as a significant modulator of BC behavior and highlight its potential as a biomarker for prognosis. Further research is warranted to elucidate the underlying mechanisms and explore the therapeutic implications of targeting CDO1 in TNBC.
乳腺癌（BC）是一种异质性疾病，预后各异，这凸显了对新型生物标志物和治疗靶点的需求。本研究调查了编码半胱氨酸双加氧酶1的CDO1基因在BC进展中的作用及其对患者预后的潜在影响。
我们在MDA-MB231三阴性乳腺癌（TNBC）细胞系中进行了CDO1的稳定转染，随后使用微阵列技术分析基因表达谱。
CDO1在转染细胞中显著上调，导致包括DEFB1、HOPX和FRMD3在内的多个肿瘤抑制基因的诱导。临床BC样本中的相关性分析揭示了CDO1与其他关键基因（包括SLC1A7和KITLG）之间的显著关联，强调了其在肿瘤生物学中的相关性。功能测定表明，CDO1表达与细胞凋亡增加和细胞活力降低相关，表明其对肿瘤进展具有保护作用。此外，我们观察到与细胞外基质和蛋白酶（SGRN和ADAMTS1）相关的致癌途径发生改变，表明CDO1可能通过基质重编程减轻转移潜能。
我们的研究结果确立了CDO1作为BC行为的重要调节因子，并突出了其作为预后生物标志物的潜力。有必要进一步研究以阐明潜在机制，并探索在TNBC中靶向CDO1的治疗意义。
