Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors and has a poor prognosis. Kelch repeat and BTB domain-containing protein 6 (KBTBD6) regulates the cytoskeleton, cell proliferation, and cell migration as part of the CUL3 (KBTBD6/7) E3 ubiquitin ligase complex, and has been associated with the development of pituitary adenomas. Here, a bioinformatics analysis was conducted using data from OSCC patients in The Cancer Genome Atlas database. Results indicate that KBTBD6 levels in OSCC patient tissues were significantly higher than in normal tissues. Additionally, high KBTBD6 expression correlated with poor prognosis. Functional annotation of differentially expressed genes associated with KBTBD6 in the OSCC cohort revealed significant enrichment of the interleukin-17 signaling pathway. Furthermore, KBTBD6 expression also correlated significantly with immune cell subset infiltration and immune checkpoint gene expression. These findings suggest that KBTBD6 is a promising therapeutic target and prognostic indicator in OSCC.
口腔鳞状细胞癌(Oral squamous cell carcinoma,OSCC)是最常见的恶性肿瘤之一,预后差。Kelch重复序列和含BTB结构域的蛋白6(KBTBD 6)作为CUL 3(KBTBD 6/7)E3泛素连接酶复合物的一部分调节细胞骨架、细胞增殖和细胞迁移,并且与垂体腺瘤的发展相关。在这里,我们进行了生物信息学分析的数据,口腔鳞癌患者在癌症基因组图谱(TCGA)数据库。我们发现KBTBD 6在口腔鳞癌患者组织中的表达水平显著高于正常组织。此外,KBTBD 6的高表达与不良预后相关。在OSCC组群中与KBTBD 6相关的差异表达基因的功能注释揭示了IL-17信号通路的显著富集。此外,KBTBD 6表达还与免疫细胞亚群和免疫检查点基因的浸润显着相关。研究结果表明,KBTBD 6可作为口腔鳞癌的一个非常有前途的作用靶点和预后指标。
Chen TW, Lee CC, Liu H, et al., 2017, APOBEC3A is an Oral Cancer Prognostic Biomarker in Taiwanese Carriers of an APOBEC Deletion Polymorphism. Nat Commun, 8(1): 465. https://doi.org/10.1038/s41467-017-00493-9
Tan Y, Wang Z, Xu M, et al., 2023, Oral Squamous Cell Carcinomas: State of the Field and Emerging Directions. Int J Oral Sci, 15(1): 44. https://doi.org/10.1038/s41368-023-00249-w
Eslami A, Miyaguchi K, Mogushi K, et al., 2015, PARVB Overexpression Increases Cell Migration Capability and Defines High Risk for Endophytic Growth and Metastasis in Tongue Squamous Cell Carcinoma. Br J Cancer, 112(2): 338-44. https://doi.org/10.1038/bjc.2014.590
Cassidy RJ, Switchenko JM, Jegadeesh N, et al., 2017, Association of Lymphovascular Space Invasion With Locoregional Failure and Survival in Patients With Node-Negative Oral Tongue Cancers. JAMA Otolaryngol Head Neck Surg, 143(4): 382–388. https://doi.org/10.1001/jamaoto.2016.3795
Zhu Y, Zhou C, He Q, 2018, Radiation Therapy’s Efficacy on Tongue Cancer: A Population-Based Survival Analysis. Onco Targets Ther, 11: 7271–7276. https://doi.org/10.2147/OTT.S169231
Genau HM, Huber J, Baschieri F, et al., 2015, CUL3-KBTBD6/KBTBD7 Ubiquitin Ligase Cooperates with GABARAP Proteins to Spatially Restrict TIAM1-RAC1 Signaling. Mol Cell, 57(6): 995–1010. https://doi.org/10.1016/j.molcel.2014.12.040
Zou Z, Zhang B, Li Z, et al., 2022, KBTBD7 Promotes Non-Small Cell Lung Carcinoma Progression by Enhancing Ubiquitin-Dependent Degradation of PTEN. Cancer Med, 11(23): 4544–4554. https://doi.org/10.1002/cam4.4794. Erratum in Cancer Med, 13(17): e7462. https://doi.org/10.1002/cam4.7462
Shi Y, Xiao Q, Huang S, et al., 2023, Poor Prognostic Biomarker KIAA1522 Is Associated with Immune Infiltrates in Hepatocellular Carcinoma. J Oncol, 2023: 3538928. https://doi.org/10.1155/2023/3538928
Du L, Li CR, He QF, et al., 2020, Downregulation of the Ubiquitin Ligase KBTBD8 Prevented Epithelial Ovarian Cancer Progression. Mol Med, 26: 96. https://doi.org/10.1186/s10020-020-00226-7
Ai F, Wang W, Liu S, et al., 2022, Integrative Proteo-Genomic Analysis for Recurrent Survival Prognosis in Colon Adenocarcinoma. Front Oncol, 12: 871568. https://doi.org/10.3389/fonc.2022.871568
Li T, Fu J, Zeng Z, et al., 2020, TIMER2.0 for Analysis of Tumor-Infiltrating Immune Cells. Nucleic Acids Res, 48(W1): W509–W514. https://doi.org/10.1093/nar/gkaa407
Vivian J, Rao AA, Nothaft FA, et al., 2017, Toil Enables Reproducible, Open Source, Big Biomedical Data Analyses. Nat Biotechnol, 35(4): 314–316. https://doi.org/10.1038/nbt.3772
Bindea G, Mlecnik B, Tosolini M, et al., 2013, Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer. Immunity, 39(4): 782–795. https://doi.org/10.1016/j.immuni.2013.10.003
Franz M, Rodriguez H, Lopes C, et al., 2018, GeneMANIA Update 2018. Nucleic Acids Res, 46(W1): W60–W64. https://doi.org/10.1093/nar/gky311
Han Y, Wang Y, Dong X, et al., 2023, TISCH2: Expanded Datasets and New Tools for Single-Cell Transcriptome Analyses of the Tumor Microenvironment. Nucleic Acids Res, 51(D1): D1425–D1431. https://doi.org/10.1093/nar/gkac959
Liu XY, Zheng CB, Wang T, et al., 2020, SPZ1 Promotes Deregulation of Bim to Boost Apoptosis Resistance in Colorectal Cancer. Clin Sci (Lond), 134(2): 155–167. https://doi.org/10.1042/CS20190865
Gharat SA, Momin M, Bhavsar C, 2016, Oral Squamous Cell Carcinoma: Current Treatment Strategies and Nanotechnology-Based Approaches for Prevention and Therapy. Crit Rev Ther Drug Carrier Syst, 33(4): 363–400. https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2016016272
Giannos P, Kechagias KS, Gal A, 2021, Identification of Prognostic Gene Biomarkers in Non-Small Cell Lung Cancer Progression by Integrated Bioinformatics Analysis. Biology (Basel), 10(11): 1200. https://doi.org/10.3390/biology10111200
Chen HM, MacDonald JA, 2022, Network Analysis of TCGA and GTEx Gene Expression Datasets for Identification of Trait-Associated Biomarkers in Human Cancer. STAR Protoc, 3(1): 101168. https://doi.org/10.1016/j.xpro.2022.101168
Chen Y, Feng Y, Yan F, et al., 2022, A Novel Immune-Related Gene Signature to Identify the Tumor Microenvironment and Prognose Disease Among Patients With Oral Squamous Cell Carcinoma Patients Using ssGSEA: A Bioinformatics and Biological Validation Study. Front Immunol, 13: 922195. https://doi.org/10.3389/fimmu.2022.922195
Blum A, Wang P, Zenklusen JC, 2018, SnapShot: TCGA-Analyzed Tumors. Cell, 173(2): 530. https://doi.org/10.1016/j.cell.2018.03.059
Shigeyasu K, Okugawa Y, Toden S, et al., 2017, Exportin-5 Functions as an Oncogene and a Potential Therapeutic Target in Colorectal Cancer. Clin Cancer Res, 23(5): 1312–1322. https://doi.org/10.1158/1078-0432.CCR-16-1023
Zhu S, Xu Z, Zeng Y, et al., 2020, ADNP Upregulation Promotes Bladder Cancer Cell Proliferation via the AKT Pathway. Front Oncol, 10: 491129. https://doi.org/10.3389/fonc.2020.491129
Saleem M, Ghazali MB, Wahab MAMA, et al., 2020, The BRCA1 and BRCA2 Genes in Early-Onset Breast Cancer Patients. Adv Exp Med Biol, 1292: 1–12. https://doi.org/10.1007/5584_2018_147
Yuan M, Tu B, Li H, et al., 2022, Cancer-Associated Fibroblasts Employ NUFIP1-Dependent Autophagy to Secrete Nucleosides and Support Pancreatic Tumor Growth. Nat Cancer, 3(8): 945–960. https://doi.org/10.1038/s43018-022-00426-6
Li X, Bechara R, Zhao J, et al., 2019, IL-17 Receptor-Based Signaling and Implications for Disease. Nat Immunol, 20(12): 1594–1602. https://doi.org/10.1038/s41590-019-0514-y
Thomas GJ, Speight PM, 2001, Cell Adhesion Molecules and Oral Cancer. Crit Rev Oral Biol Med, 12(6): 479–498. https://doi.org/10.1177/10454411010120060301
Li R, Zhou Y, Zhang M, et al., 2023, Oral Squamous Cell Carcinoma-Derived EVs Promote Tumor Progression by Regulating Inflammatory Cytokines and the IL-17A-Induced Signaling Pathway. Int Immunopharmacol, 118: 110094. https://doi.org/10.1016/j.intimp.2023.110094
Lu D, Gao Y, 2022, Immune Checkpoint Inhibitor-related Endocrinopathies. J Transl Int Med, 10(1): 9–14. https://doi.org/10.2478/jtim-2022-0009
Sen S, Carnelio S, 2016, Expression of Epithelial Cell Adhesion Molecule (EpCAM) in Oral Squamous Cell Carcinoma. Histopathology, 68(6): 897–904. https://doi.org/10.1111/his.12870
Xie L, Fang J, Yu J, et al., 2023, The Role of CD4+ T Cells in Tumor and Chronic Viral Immune Responses. MedComm (2020), 4(5): e390. https://doi.org/10.1002/mco2.390
Chen X, Wang M, Yu K, et al., 2022, Chronic Stress-Induced Immune Dysregulation in Breast Cancer: Implications of Psychosocial Factors. J Transl Int Med, 11(3): 226–233. https://doi.org/10.2478/jtim-2021-0050
Duraiswamy J, Freeman GJ, Coukos G, 2013, Therapeutic PD-1 Pathway Blockade Augments with Other Modalities of Immunotherapy T-Cell Function to Prevent Immune Decline in Ovarian Cancer. Cancer Res, 73(23): 6900–6912. https://doi.org/10.1158/0008-5472.CAN-13-1550
Van der Leun AM, Thommen DS, Schumacher TN, 2020, CD8+ T Cell States in Human Cancer: Insights from Single-Cell Analysis. Nat Rev Cancer, 20(4): 218–232. https://doi.org/10.1038/s41568-019-0235-4
Tian Z, Ou G, Su M, et al., 2022, TIMP1 Derived from Pancreatic Cancer Cells Stimulates Schwann Cells and Promotes the Occurrence of Perineural Invasion. Cancer Lett, 546: 215863. https://doi.org/10.1016/j.canlet.2022.215863
Kang JH, Zappasodi R, 2023, Modulating Treg Stability to Improve Cancer Immunotherapy. Trends Cancer, 9(11): 911–927. https://doi.org/10.1016/j.trecan.2023.07.015