C1orf50 在乳腺癌进展和预后中的作用。

IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Breast Cancer Pub Date : 2024-11-28 DOI:10.1007/s12282-024-01653-8
Yusuke Otani, Atsushi Tanaka, Masaki Maekawa, Tirso Peña, Anna Rogachevskaya, Teruhiko Ando, Takuto Itano, Haruyoshi Katayama, Eiji Nakata, Toshifumi Ozaki, Shinichi Toyooka, Hiroyoshi Doihara, Michael H Roehrl, Atsushi Fujimura
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引用次数: 0

摘要

尽管与其他癌症相比,乳腺癌的预后已明显改善,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,以便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,尤其是那些 Luminal A 型乳腺癌患者。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和体外分析揭示了受C1orf50表达影响的分子通路。C1orf50敲除抑制了乳腺癌细胞的细胞周期,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,研究还发现 C1orf50 在乳腺癌细胞中的含量高于正常乳腺上皮细胞,这表明 C1orf50 与乳腺癌的发病机制有关。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通过细胞周期上调、维持癌症干性和免疫逃避机制促进乳腺癌的进展。我们的研究揭示了C1orf50在腔隙型乳腺癌进展过程中的生物学功能,这是以前在任何类型的癌症中都没有报道过的发现。
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The role of C1orf50 in breast cancer progression and prognosis.

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.

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来源期刊
Breast Cancer
Breast Cancer ONCOLOGY-OBSTETRICS & GYNECOLOGY
CiteScore
6.70
自引率
2.50%
发文量
105
审稿时长
6-12 weeks
期刊介绍: Breast Cancer, the official journal of the Japanese Breast Cancer Society, publishes articles that contribute to progress in the field, in basic or translational research and also in clinical research, seeking to develop a new focus and new perspectives for all who are concerned with breast cancer. The journal welcomes all original articles describing clinical and epidemiological studies and laboratory investigations regarding breast cancer and related diseases. The journal will consider five types of articles: editorials, review articles, original articles, case reports, and rapid communications. Although editorials and review articles will principally be solicited by the editors, they can also be submitted for peer review, as in the case of original articles. The journal provides the best of up-to-date information on breast cancer, presenting readers with high-impact, original work focusing on pivotal issues.
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