Otani Yusuke, Tanaka Atsushi, Maekawa Masaki, Peña Tirso, Rogachevskaya Anna, Ando Teruhiko, Itano Takuto, Katayama Haruyoshi, Nakata Eiji, Ozaki Toshifumi, Toyooka Shinichi, Doihara Hiroyoshi, Roehrl Michael H, Fujimura Atsushi
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Breast Cancer. 2025 Mar;32(2):292-305. doi: 10.1007/s12282-024-01653-8. Epub 2024 Nov 28.
Although the prognosis of breast cancer has significantly improved compared to other types of cancer, there are still some patients who expire due to recurrence or metastasis. Therefore, it is necessary to develop a method to identify patients with poor prognosis at the early stages of cancer. In the process of discovering new prognostic markers from genes of unknown function, we found that the expression of C1orf50 determines the prognosis of breast cancer patients, especially for those with Luminal A breast cancer. This study aims to elucidate the molecular role of C1orf50 in breast cancer progression. Bioinformatic analyses of the breast cancer dataset of TCGA, and in vitro analyses, reveal the molecular pathways influenced by C1orf50 expression. C1orf50 knockdown suppressed the cell cycle of breast cancer cells and weakened their ability to maintain the undifferentiated state and self-renewal capacity. Interestingly, upregulation of C1orf50 increased sensitivity to CDK4/6 inhibition. In addition, C1orf50 was found to be more abundant in breast cancer cells than in normal breast epithelium, suggesting C1orf50's involvement in breast cancer pathogenesis. Furthermore, the mRNA expression level of C1orf50 was positively correlated with the expression of PD-L1 and its related factors. These results suggest that C1orf50 promotes breast cancer progression through cell cycle upregulation, maintenance of cancer stemness, and immune evasion mechanisms. Our study uncovers the biological functions of C1orf50 in Luminal breast cancer progression, a finding not previously reported in any type of cancer.
尽管与其他类型的癌症相比，乳腺癌的预后有了显著改善，但仍有一些患者因复发或转移而死亡。因此，有必要开发一种方法来在癌症早期识别预后不良的患者。在从功能未知的基因中发现新的预后标志物的过程中，我们发现C1orf50的表达决定了乳腺癌患者的预后，尤其是对于那些患有Luminal A型乳腺癌的患者。本研究旨在阐明C1orf50在乳腺癌进展中的分子作用。对TCGA乳腺癌数据集的生物信息学分析以及体外分析揭示了受C1orf50表达影响的分子途径。C1orf50基因敲低抑制了乳腺癌细胞的细胞周期，并削弱了它们维持未分化状态和自我更新能力。有趣的是，C1orf50的上调增加了对CDK4/6抑制的敏感性。此外，发现C1orf50在乳腺癌细胞中比在正常乳腺上皮中更丰富，这表明C1orf50参与了乳腺癌的发病机制。此外，C1orf50的mRNA表达水平与PD-L1及其相关因子的表达呈正相关。这些结果表明，C1orf50通过上调细胞周期、维持癌症干性和免疫逃逸机制促进乳腺癌进展。我们的研究揭示了C1orf50在Luminal型乳腺癌进展中的生物学功能，这一发现在任何类型的癌症中都未曾报道过。
