|
|
基于COMMD10基因在三阴性乳腺癌中构建CD8+T细胞相关的预后模型
|
Abstract:
目的：为探索COMMD10基因在三阴性乳腺癌(TNBC)治疗与预后中的作用，我们构建了一个基于COMMD10相关基因的预后模型。该模型旨在帮助评估患者的生存情况并制定治疗方案。方法：研究数据来自GEO和TCGA数据库，纳入TNBC患者的基因表达数据及临床信息。我们首先通过Spearman相关性分析筛选出78个与COMMD10表达相关的基因，通过LASSO多因素COX回归分析识别独立预后基因并构建风险评分。结果：筛选了5个关键基因用于构建风险评分模型，根据这些基因构建的风险评分模型，能将患者分为高风险组和低风险组。通过生存曲线和ROC曲线验证发现，该模型在训练集和验证集中均表现良好。进一步分析显示，高低风险组患者的免疫细胞浸润程度、免疫检查点分子表达以及化疗药物敏感性存在显著差异。结论：这些发现表明，COMMD10相关模型不仅能预测TNBC患者的预后，还能为个性化治疗提供依据。
Objective: To explore the role of COMMD10 gene in the treatment and prognosis of triple-negative breast cancer (TNBC), we constructed a prognostic model based on COMMD10-related genes. The model was designed to help assess patient survival and develop a treatment plan. Methods: Data were obtained from the GEO and TCGA databases, which contain gene expression data and clinical information of TNBC patients. We first screened 78 genes associated with COMMD10 expression by Spearman correlation analysis, identified independent prognostic genes, and constructed risk scores by LASSO multifactorial COX regression analysis. Results: Five key genes were selected for risk score model construction, and the risk score models constructed based on these genes were able to classify patients into high-risk and low-risk groups. The model was validated using survival curves and ROC curves and was found to perform well in both the training and validation sets. Further analysis revealed significant differences in the degree of immune cell infiltration, expression of immune checkpoint molecules, and chemotherapeutic drug sensitivity between patients in the high-risk and low-risk groups. Conclusion: These results suggest that the COMMD10-related model can not only predict the prognosis of TNBC patients, but also provide a basis for personalized treatment.
| [1] | Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. https://doi.org/10.3322/caac.21660 |
| [2] | Ferrari, P., Scatena, C., Ghilli, M., Bargagna, I., Lorenzini, G. and Nicolini, A. (2022) Molecular Mechanisms, Biomarkers and Emerging Therapies for Chemotherapy Resistant TNBC. International Journal of Molecular Sciences, 23, Article 1665. https://doi.org/10.3390/ijms23031665 |
| [3] | Maine, G.N. and Burstein, E. (2007) COMMD Proteins: COMMing to the Scene. Cellular and Molecular Life Sciences, 64, 1997-2005. https://doi.org/10.1007/s00018-007-7078-y |
| [4] | Shirai, T., Nakai, A., Ando, E., Fujimoto, J., Leach, S., Arimori, T., et al. (2023) Celastrol Suppresses Humoral Immune Responses and Autoimmunity by Targeting the COMMD3/8 Complex. Science Immunology, 8, eadc9324. https://doi.org/10.1126/sciimmunol.adc9324 |
| [5] | Corbee, R.J. and Penning, L.C. (2021) COMMD1 Exemplifies the Power of Inbred Dogs to Dissect Genetic Causes of Rare Copper-Related Disorders. Animals, 11, Article 601. https://doi.org/10.3390/ani11030601 |
| [6] | Healy, M.D., McNally, K.E., Butkovič, R., Chilton, M., Kato, K., Sacharz, J., et al. (2023) Structure of the Endosomal Commander Complex Linked to Ritscher-Schinzel Syndrome. Cell, 186, 2219-2237.e29. |
| [7] | Yang, S.S., Li, X.M., Yang, M., Ren, X.L., Hu, J.L., Zhu, X.H., et al. (2017) FMNL2 Destabilises COMMD10 to Activate NF-κB Pathway in Invasion and Metastasis of Colorectal Cancer. British Journal of Cancer, 117, 1164-1175. https://doi.org/10.1038/bjc.2017.260 |
| [8] | Yang, M., Wu, X., Hu, J., Wang, Y., Wang, Y., Zhang, L., et al. (2022) COMMD10 Inhibits HiF1α/CP Loop to Enhance Ferroptosis and Radiosensitivity by Disrupting Cu-Fe Balance in Hepatocellular Carcinoma. Journal of Hepatology, 76, 1138-1150. https://doi.org/10.1016/j.jhep.2022.01.009 |
| [9] | Liu, X., Mao, X., Zhu, C., Liu, H., Fang, Y., Fu, T., et al. (2024) COMMD10 Inhibited DNA Damage to Promote the Progression of Gastric Cancer. Journal of Cancer Research and Clinical Oncology, 150, Article No. 305. https://doi.org/10.1007/s00432-024-05817-z |
| [10] | Fan, Y., Zhang, L., Sun, Y., Yang, M., Wang, X., Wu, X., et al. (2019) Expression Profile and Bioinformatics Analysis of COMMD10 in BALB/C Mice and Human. Cancer Gene Therapy, 27, 216-225. https://doi.org/10.1038/s41417-019-0087-9 |
| [11] | 张思维, 郑荣寿, 孙可欣, 等. 2016年中国恶性肿瘤分地区发病和死亡估计: 基于人群的肿瘤登记数据分析[J].中国肿瘤, 2023, 32(5): 321-332. |
| [12] | Rakha, E.A. and Ellis, I.O. (2011) Modern Classification of Breast Cancer: Should We Stick with Morphology or Convert to Molecular Profile Characteristics. Advances in Anatomic Pathology, 18, 255-267. https://doi.org/10.1097/pap.0b013e318220f5d1 |
| [13] | Diaz, L.K., Cryns, V.L., Symmans, W.F. and Sneige, N. (2007) Triple Negative Breast Carcinoma and the Basal Phenotype: From Expression Profiling to Clinical Practice. Advances in Anatomic Pathology, 14, 419-430. https://doi.org/10.1097/pap.0b013e3181594733 |
| [14] | Taylor, C., Dodwell, D., McGale, P., Hills, R.K., Berry, R., Bradley, R., et al. (2023) Radiotherapy to Regional Nodes in Early Breast Cancer: An Individual Patient Data Meta-Analysis of 14 324 Women in 16 Trials. The Lancet, 402, 1991-2003. https://doi.org/10.1016/s0140-6736(23)01082-6 |
| [15] | Chang, C.A., Jen, J., Jiang, S., Sayad, A., Mer, A.S., Brown, K.R., et al. (2021) Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer. Cancer Discovery, 12, 1022-1045. https://doi.org/10.1158/2159-8290.cd-20-1265 |
| [16] | Sikov, W.M., Berry, D.A., Perou, C.M., Singh, B., Cirrincione, C.T., Tolaney, S.M., et al. (2015) Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-Per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance). Journal of Clinical Oncology, 33, 13-21. https://doi.org/10.1200/jco.2014.57.0572 |
| [17] | Zhao, Z., Li, Y., Liu, H., Jain, A., Patel, P.V. and Cheng, K. (2020) Co-Delivery of IKBKE siRNA and Cabazitaxel by Hybrid Nanocomplex Inhibits Invasiveness and Growth of Triple-Negative Breast Cancer. Science Advances, 6, eabb0616. https://doi.org/10.1126/sciadv.abb0616 |
| [18] | Ni, Y., Schmidt, K.R., Werner, B.A., Koenig, J.K., Guldner, I.H., Schnepp, P.M., et al. (2019) Death Effector Domain-Containing Protein Induces Vulnerability to Cell Cycle Inhibition in Triple-Negative Breast Cancer. Nature Communications, 10, Article No. 2860. https://doi.org/10.1038/s41467-019-10743-7 |
| [19] | Xu, J., Sun, J., Ho, P.Y., Luo, Z., Ma, W., Zhao, W., et al. (2019) Creatine Based Polymer for Codelivery of Bioengineered Microrna and Chemodrugs against Breast Cancer Lung Metastasis. Biomaterials, 210, 25-40. https://doi.org/10.1016/j.biomaterials.2019.04.025 |
| [20] | Wang, N., Gu, Y., Chi, J., Liu, X., Xiong, Y., Zhong, C., et al. (2021) Screening of DNA Damage Repair Genes Involved in the Prognosis of Triple-Negative Breast Cancer Patients Based on Bioinformatics. Frontiers in Genetics, 12, Article 721873. https://doi.org/10.3389/fgene.2021.721873 |
| [21] | Peng, W., Lin, C., Jing, S., Su, G., Jin, X., Di, G., et al. (2021) A Novel Seven Gene Signature-Based Prognostic Model to Predict Distant Metastasis of Lymph Node-Negative Triple-Negative Breast Cancer. Frontiers in Oncology, 11, Article 746763. https://doi.org/10.3389/fonc.2021.746763 |
| [22] | Kim, E., Kim, Y., Ji, Z., Kang, J.M., Wirianto, M., Paudel, K.R., et al. (2022) ROR Activation by Nobiletin Enhances Antitumor Efficacy via Suppression of IκB/NF-κB Signaling in Triple-Negative Breast Cancer. Cell Death & Disease, 13, Article No. 374. https://doi.org/10.1038/s41419-022-04826-5 |
