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基于生物信息学分析LY6D在胰腺癌中的表达、发病机制及预后评估价值
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Abstract:
目的：探究LY6D在胰腺癌中的表达、预后意义，以及致病机制，并构建预后评估模型。方法：Timer2.0在线网站分析LY6D在各种肿瘤中的表达，GEO数据集分析LY6D在胰腺癌中的表达。cbioportal分析LY6D突变对胰腺癌患者预后的影响，Kaplan-Meier Plotter在线网站分析LY6D表达对胰腺癌患者预后的影响，GSEA富集分析探索LY6D在胰腺癌中参与的信号通路，STRING数据库构建PPI网络探究与LY6D关系密切的基因，最后利用与胰腺癌预后显著相关的基因构建预后模型。结果：LY6D在胰腺癌中显著高表达，且LY6D高表达患者具有较差预后，同时LY6D突变胰腺癌患者具有较差预后，LY6D富集到细胞粘附通路中，通过促进癌细胞粘附和扩散促进癌症的进展，基于LY6D、PSCA、MSLN构建的预后模型对胰腺癌患者预后评估具有显著意义。结论：LY6D有望成为胰腺癌早期诊断的重要标志物和作为分子治疗的重要靶点。基于LY6D、MSLN、PSCA构建的预后模型对胰腺癌患者预后具有较好的评估价值。
Object: To investigate the expression, prognostic significance and pathogenesis of LY6D in pancreatic adenocarcinoma, and to establish a prognostic evaluation model. Methods: Timer2 database was used to analyze the expression of LY6D in various tumors and GEO data sets were used to analyze the expression of LY6D in pancreatic adenocarcinoma. Cbioportal website was used to analyze the effect of LY6D mutation on the prognosis of patients with pancreatic adenocarcinoma. The Kaplan-Meier Plotter online website analyzed the effect of LY6D expression on the prognosis of pancreatic adenocarcinoma patients. GSEA enrichment analysis explored the signal pathway of LY6D in pancreatic adenocarcinoma. The PPI network was constructed with string database to explore the genes closely related to LY6D. Finally, a prognostic model was constructed based on the genes associated with the prognosis of pancreatic adenocarcinoma. Results: LY6D was highly expressed in pancreatic adenocarcinoma, and patients with high LY6D expression had poor prognosis. Meanwhile, patients with pancreatic adenocarcinoma with LY6D mutation have poor prognosis. LY6D is enriched into the cell adhesion pathway and promotes the progression of cancer by promoting the adhesion and proliferation of cancer cells. The prognosis model based on LY6D, PSCA and MSLN has significant significance in the prognosis evaluation of pancreatic adenocarcinoma patients. Conclusion: LY6D is expected to be an important marker for early diagnosis of pancreatic adenocarcinoma and an important target for molecular therapy. The prognosis model based on LY6D, MSLN and PSCA has significant value in predicting the prognosis of patients with pancreatic adenocarcinoma.
| [1] | 中国抗癌协会胰腺癌专业委员会. 中国胰腺癌综合诊治指南(2020版) [J]. 中华外科杂志, 2021, 59(2): 81-100. |
| [2] | Sung, H., Jacques, F., 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 |
| [3] | Siegel, R.L., Miller, K.D., Fuchs, H.E. and Jemal, A. (2021) Cancer Statistics, 2021. CA: A Cancer Journal for Clinicians, 71, 7-33. https://doi.org/10.3322/caac.21654 |
| [4] | 蔡洁, 陈宏达, 卢明, 等. 2005-2015年中国胰腺癌发病与死亡趋势分析[J]. 中华流行病学杂志, 2021, 42(5): 794-800. |
| [5] | Brakenhoff, R.-H., Gerretsen, M., Knippels, E.-M., et al. (1995) The Human E48 Antigen, Highly Homologous to the Murine Ly-6 Antigen ThB, Is a GPI-Anchored Molecule Apparently Involved in Keratinocyte Cell-Cell Adhesion. Journal of Cell Biology, 129, 1677-1689. https://doi.org/10.1083/jcb.129.6.1677 |
| [6] | Colnot, D.R., Nieuwenhuis, E.J.C., Kuik, D.J., et al. (2004) Clinical Significance of Micrometastatic Cells Detected by E48 (Ly-6D) Reverse Transcription-Polymerase Chain Reaction in Bone Marrow of Head and Neck Cancer Patients. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 10, 7827-7833.
https://doi.org/10.1158/1078-0432.CCR-04-1090 |
| [7] | Wang, J., Fan, J., Gao, W., et al. (2020) LY6D as a Chemoresistance Marker Gene and Therapeutic Target for Laryngeal Squamous Cell Carcinoma. Stem Cells and Development, 29, 774-785. |
| [8] | Barros-Silva, J.-D., Linn, D.E., Steiner, I., et al. (2018) Single-Cell Analysis Identifies LY6D as a Marker Linking Castration-Resistant Prostate Luminal Cells to Prostate Progenitors and Cancer. Cell Reports, 25, 3504-3518.
https://doi.org/10.1016/j.celrep.2018.11.069 |
| [9] | Mayama, A., Kiyoshi, T., Hiroyoshi, S., et al. (2018) OLFM4, LY6D and S100A7 as Potent Markers for Distant Metastasis in Estrogen Receptor-Positive Breast Carcinoma. Cancer Science, 109, 3350-3359.
https://doi.org/10.1111/cas.13770 |
| [10] | Semba, T., Ryo, S., Akiyoshi, K., et al. (2020) Lung Adenocarcinoma Mouse Models Based on Orthotopic Transplantation of Syngeneic Tumor-Initiating Cells Expressing EpCAM, SCA-1, and Ly6d. Cancers, 12, 3805.
https://doi.org/10.3390/cancers12123805 |
| [11] | Li, T.W., Fu, J.X., Zeng, Z.X., et al. (2020) TIMER2.0 for Analysis of Tumor-Infiltrating Immune Cells. Nucleic Acids Research, 48, W509-W514. https://doi.org/10.1093/nar/gkaa407 |
| [12] | Thul, P.J. and Cecilia, L. (2018) The Human Protein Atlas: A Spatial Map of the Human Proteome. Protein Science, 27, 233-244. https://doi.org/10.1002/pro.3307 |
| [13] | Cerami, E., Gao, J.J., Dogrusoz, U., et al. (2012) The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data: Figure 1. Cancer Discovery, 2, 401-404.
https://doi.org/10.1158/2159-8290.CD-12-0095 |
| [14] | Szklarczyk, D., Gable, A.L., Lyon, D., et al. (2019) STRING v11: Protein-Protein Association Networks with Increased Coverage, Supporting Functional Discovery in Genome-Wide Experimental Datasets. Nucleic Acids Research, 47, D607-D613. https://doi.org/10.1093/nar/gky1131 |
| [15] | Nagy, á., Gy？ngyi, M. and Balázs, G. (2021) Pancancer Survival Analysis of Cancer Hallmark Genes. Scientific Reports, 11, Article No. 6047. |
| [16] | Zhang, Z., Lin, E., Zhuang, H., et al. (2020) Construction of a Novel Gene-Based Model for Prognosis Prediction of Clear Cell Renal Cell Carcinoma. Cancer Cell International, 20, 27. https://doi.org/10.1186/s12935-020-1113-6 |
| [17] | Gupta, N. and Raghav, Y. (2021) Pancreatic Adenocarcinoma: A Review of Recent Paradigms and Advances in Epidemiology, Clinical Diagnosis and Management. World Journal of Gastroenterology, 27, 3158-3181.
https://doi.org/10.3748/wjg.v27.i23.3158 |
| [18] | 范红星, 倪建勋, 薄彪, 等. 术前白蛋白-胆红素评分以及其与CA19-9联合作为胰腺癌患者预后指标的临床价值[J]. 中国普通外科杂志, 2020, 29(3): 310-316. |
| [19] | Nagano, T., Tetsushi, I., Kengo, O., et al. (2021) LY6D-Induced Macropinocytosis as a Survival Mechanism of Senescent Cells. Journal of Biological Chemistry, 296, Article ID: 100049. https://doi.org/10.1074/jbc.RA120.013500 |
| [20] | Wang, J., Fan, J.M., Gao, W., et al. (2020) LY6D as a Chemoresistance Marker Gene and Therapeutic Target for Laryngeal Squamous Cell Carcinoma. Stem Cells and Development, 29, 774-785. https://doi.org/10.1089/scd.2019.0210 |
| [21] | Xiang, Q., Zhu, Z.G., Luo, L.M., et al. (2020) The Correlation between PSCA Expression and Neuroendocrine Differentiation in Prostate Cancer. BioMed Research International, 2020, Article ID: 5395312.
https://doi.org/10.1155/2020/5395312 |
| [22] | Yan, K.P., Kun, W., Chao, L., et al. (2019) Impact of PSCA Gene Polymorphisms in Modulating Gastric Cancer Risk in the Chinese Population. Bioscience Reports, 39, BSR20181025. https://doi.org/10.1042/BSR20181025 |
| [23] | Heinrichs, S.-K-.M., Hess, T., Becker, J., et al. (2018) Evidence for PTGER4, PSCA, and MBOAT7 as Risk Genes for Gastric Cancer on the Genome and Transcriptome Level. Cancer Medicine, 7, 5057-5065. |
| [24] | Kendrick, Z.W., Firpo, M.A., Repko, R.C., et al. (2014) Serum IGFBP2 and MSLN as Diagnostic and Prognostic Biomarkers for Pancreatic Cancer]. HPB: The Official Journal of the International Hepato Pancreato Biliary Association, 16, 670-676. https://doi.org/10.1111/hpb.12199 |
| [25] | Althouse, A.D. (2016) Statistical Graphics in Action: Making Better Sense of the ROC Curve. International Journal of Cardiology, 215, 9-10. |
