Background: Uveal melanoma (UVM) is the most common primary intraocular tumor in adults. However, identification of the effective biomarker for the diagnosis and treatment of UVM remains to be explored. Calcium and integrin-binding protein 1 (CIB1) is emerging as an important factor in tumor progression. Purpose: To determine the contribution of CIB1 in the diagnosis of UVM. Method: Immunohistochemical staining is used to detect the CIB1 expression level, while Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and UALCAN online tools were used to analyze patient survival and CIB1 correlation genes in UVM. Integrative analysis using STRING and GeneMANIA predicted the correlated genes with CIB1 in UVM. Results: CIB1 expression level in UVM was significantly enhanced when compared with that in paracancerous tissues. A higher CIB1 expression level resulted in a significantly worse disease-free survival as well as overall survival. Moreover, the survival probability of patients was associated with body weight and gender of the patients with UVM. The correlated genes with CIB1 in UVM, and the similarity of the genes in UVM expression and survival heatmap were verified. Furthermore, Gene ontology enrichment analysis revealed that CIB1 and its correlated genes are significantly enriched in ITGA2B-ITGB3-CIB1 complex, regulation of intracellular protein transport and regulation of ion transport. Conclusions: Our novel findings suggested that CIB1 might be a potential diagnostic predictor for UVM, and might contribute to the potential strategy for UVM treatment by targeting CIB1
References
[1]
Shain, A.H., Bagger, M.M., Yu, R., Chang, D., Liu, S., Vemula, S., et al. (2019) The Genetic Evolution of Metastatic Uveal Melanoma. Nature Genetics, 51, 1123-1130. https://doi.org/10.1038/s41588-019-0440-9
[2]
Carvajal, R.D., Schwartz, G.K., Tezel, T., Marr, B., Francis, J.H. and Nathan, P.D. (2017) Metastatic Disease from Uveal Melanoma: Treatment Options and Future Prospects. British Journal of Ophthalmology, 101, 38-44. https://doi.org/10.1136/bjophthalmol-2016-309034
[3]
Vasalaki, M., Fabian, I.D., Reddy, M.A., Cohen, V.M. and Sagoo, M.S. (2017) Ocular Oncology: Advances in Retinoblastoma, Uveal Melanoma and Conjunctival Melanoma. British Medical Bulletin, 121, 107-119. https://doi.org/10.1093/bmb/ldw053
[4]
Komatsubara, K.M. and Carvajal, R.D. (2017) Immunotherapy for the Treatment of Uveal Melanoma: Current Status and Emerging Therapies. Current Oncology Reports, 19, Article No. 45. https://doi.org/10.1007/s11912-017-0606-5
[5]
Pham, C.M., Custer, P.L. and Couch, S.M. (2017) Comparison of Primary and Secondary Enucleation for Uveal Melanoma. Orbit (Amsterdam, Netherlands), 36, 422-427. https://doi.org/10.1080/01676830.2017.1337183
[6]
Hager, A., Meissner, F., Riechardt, A.I., Bonaventura, T., Lowen, J. and Heufelder, J. (2019) Breakdown of the Blood-Eye Barrier in Choroidal Melanoma after Proton Beam Radiotherapy. Graefe’s Archive for Clinical and Experimental Ophthalmology, 257, 2323-2328. https://doi.org/10.1007/s00417-019-04413-z
[7]
Li, Y., Xu, Y., Peng, X., Huang, J., Yang, M. and Wang, X. (2019) A Novel Photosensitizer Znln2S4 Mediated Photodynamic Therapy Induced-HepG2 Cell Apoptosis. Radiation Research, 192, 422-430. https://doi.org/10.1667/RR15389.1
[8]
Castet F., Garcia-Mulero, S., Sanz-Pamplona, R., Cuellar, A., Casanovas, O., Caminal, J.M., et al. (2019) Uveal Melanoma, Angiogenesis and Immunotherapy, Is There Any Hope? Cancers, 11, Article No. 834. https://doi.org/10.3390/cancers11060834
[9]
Hughes, S., Damato, B.E., Giddings, I., Hiscott, P.S., Humphreys, J. and Houlston, R.S. (2005) Microarray Comparative Genomic Hybridisation Analysis of Intraocular Uveal Melanomas Identifies Distinctive Imbalances Associated with Loss of Chromosome 3. British Journal of Cancer, 93, 1191-1196. https://doi.org/10.1038/sj.bjc.6602834
[10]
Minca, E.C., Tubbs, R.R., Portier, B.P., Wang, Z., Lanigan, C., Aronow, M.E., et al. (2014) Genomic Microarray Analysis on Formalin-Fixed Paraffin-Embedded Material for Uveal Melanoma Prognostication. Cancer Genetics, 207, 306-315. https://doi.org/10.1016/j.cancergen.2014.08.005
[11]
Wang, X., Peng, X., Zhang, X., Xu, H., Lu, C., Liu, L., et al. (2017) The Emerging Roles of CIB1 in Cancer. Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 43, 1413-1424. https://doi.org/10.1159/000481873
[12]
Zayed, M.A., Yuan, W., Chalothorn, D., Faber, J.E. and Parise, L.V. (2010) Tumor Growth and Angiogenesis Is Impaired in CIB1 Knockout Mice. Journal of Angiogenesis Research, 2, Article No. 17. https://doi.org/10.1186/2040-2384-2-17
[13]
Zayed, M.A., Yuan, W., Leisner, T.M., Chalothorn, D., McFadden, A.W., Schaller, M.D., et al. (2007) CIB1 Regulates Endothelial Cells and Ischemia-Induced Pathological and Adaptive Angiogenesis. Circulation Research, 101, 1185-1193. https://doi.org/10.1161/CIRCRESAHA.107.157586
[14]
Zhu, W., Gliddon, B.L., Jarman, K.E., Moretti, P.A.B., Tin, T., Parise, L.V., et al. (2017) CIB1 Contributes to Oncogenic Signalling by Ras via Modulating the Subcellular Localisation of Sphingosine Kinase 1. Oncogene, 36, 2619-2627. https://doi.org/10.1038/onc.2016.428
[15]
Chung, A.H., Leisner, T.M., Dardis, G.J., Bivins, M.M., Keller, A.L. and Parise, L.V. (2019) CIB1 Depletion with Docetaxel or TRAIL Enhances Triple-Negative Breast Cancer Cell Death. Cancer Cell International, 19, Article No. 26. https://doi.org/10.1186/s12935-019-0740-2
[16]
Chandrashekar D.S., Bashel, B., Balasubramanya, S.A.H., Creighton, C.J., Ponce-Rodriguez, I., Chakravarthi, B., et al. (2017) UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia (New York, N.Y.), 19, 649-658. https://doi.org/10.1016/j.neo.2017.05.002
[17]
Tang, Z., Li, C., Kang, B., Gao, G., Li, C. and Zhang, Z. (2017) GEPIA: A Web Server for Cancer and Normal Gene Expression Profiling and Interactive Analyses. Nucleic Acids Research, 45, W98-W102. https://doi.org/10.1093/nar/gkx247
[18]
Szklarczyk, D., Franceschini, A., Wyder, S., Forslund, K., Heller, D., Huerta-Cepas, J., et al. (2015) STRING v10: Protein-Protein Interaction Networks, Integrated over the Tree of Life. Nucleic Acids Research, 43, D447-D452. https://doi.org/10.1093/nar/gku1003
[19]
Franz, M., Rodriguez, H., Lopes, C., Zuberi, K., Montojo, J., Bader, G.D., et al. (2018) GeneMANIA Update 2018. Nucleic Acids Research, 46, W60-W64. https://doi.org/10.1093/nar/gky311
[20]
Zhou, Y., Zhou, B., Pache, L., Chang, M., Khodabakhshi, A.H., Tanaseichuk, O., et al. (2019) Metascape Provides a Biologist-Oriented Resource for the Analysis of Systems-Level Datasets. Nature Communications, 10, Article No. 1523. https://doi.org/10.1038/s41467-019-09234-6
[21]
Gao, J., Aksoy, B.A., Dogrusoz, U., Dresdner, G., Gross, B., Sumer, S.O., et al. (2013) Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal. Science Signaling, 6, pl1. https://doi.org/10.1126/scisignal.2004088
[22]
Ehrlich, M. and Lacey, M. (2013) DNA Methylation and Differentiation: Silencing, Upregulation and Modulation of Gene Expression. Epigenomics, 5, 553-568. https://doi.org/10.2217/epi.13.43
[23]
Bauerschmitt, H., Funes, S. and Herrmann, J.M. (2008) The Membrane-Bound GTPase Guf1 Promotes Mitochondrial Protein Synthesis under Suboptimal Conditions. The Journal of Biological Chemistry, 283, 17139-17146. https://doi.org/10.1074/jbc.M710037200
[24]
Kriebs, A., Jordan, S.D., Soto, E., Henriksson, E., Sandate, C.R., Vaughan, M.E., et al. (2017) Circadian Repressors CRY1 and CRY2 Broadly Interact with Nuclear Receptors and Modulate Transcriptional Activity. Proceedings of the National Academy of Sciences of the United States of America, 114, 8776-8781. https://doi.org/10.1073/pnas.1704955114
[25]
Seban, R.D., Nemer, J.S., Marabelle, A., Yeh, R., Deutsch, E., Ammari, S., et al. (2019) Prognostic and Theranostic 18F-FDG PET Biomarkers for Anti-PD1 Immunotherapy in Metastatic Melanoma: Association with Outcome and Transcriptomics. European Journal of Nuclear Medicine and Molecular Imaging, 46, 2298-2310. https://doi.org/10.1007/s00259-019-04411-7
[26]
Xu, Y., Han, W., Xu, W.H., Wang, Y., Yang, X.L., Nie, H.L., et al. (2019) Identification of Differentially Expressed Genes and Functional Annotations Associated with Metastases of the Uveal Melanoma. Journal of Cellular Biochemistry, 120, 19202-19214. https://doi.org/10.1002/jcb.29250
[27]
Londin, E., Magee, R., Shields, C.L., Lally, S.E., Sato, T. and Rigoutsos, I. (2019) IsomiRs and tRNA-Derived Fragments Are Associated with Metastasis and Patient Survival in Uveal Melanoma. Pigment Cell & Melanoma Research, 33, 52-62. https://doi.org/10.1111/pcmr.12810
[28]
Wan, Q., Tang, J., Han, Y. and Wang, D. (2018) Co-Expression Modules Construction by WGCNA and Identify Potential Prognostic Markers of Uveal Melanoma. Experimental Eye Research, 166, 13-20. https://doi.org/10.1016/j.exer.2017.10.007
[29]
Iyengar, N.M., Gucalp, A., Dannenberg, A.J. and Hudis, C.A. (2016) Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 34, 4270-4276. https://doi.org/10.1200/JCO.2016.67.4283
[30]
Kim, Y.J., Bond, G.J., Tsang, T., Posimo, J.M., Busino, L. and Brady, D.C. (2019) Copper Chaperone ATOX1 Is Required for MAPK Signaling and Growth in BRAF Mutation-Positive Melanoma. Metallomics, 11, 1430-1440. https://doi.org/10.1039/c9mt00042a
[31]
Richman, T.R., Ermer, J.A., Davies, S.M., Perks, K.L., Viola, H.M., Shearwood, A.M., et al. (2015) Mutation in MRPS34 Compromises Protein Synthesis and Causes Mitochondrial Dysfunction. PLOS Genetics, 11, e1005089. https://doi.org/10.1371/journal.pgen.1005089
[32]
Stabler, S.M., Ostrowski, L.L., Janicki, S.M. and Monteiro, M.J. (1999) A Myristoylated Calcium-Binding Protein That Preferentially Interacts with the Alzheimer’s Disease Presenilin 2 Protein. The Journal of Cell Biology, 145, 1277-1292. https://doi.org/10.1083/jcb.145.6.1277
[33]
Clark, O., Yen, K. and Mellinghoff, I.K. (2016) Molecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 22, 1837-1842. https://doi.org/10.1158/1078-0432.CCR-13-1333
[34]
Fomchenko, E.I., Erson-Omay, E.Z. and Moliterno, J. (2019) A Novel Finding of an IDH2 Mutation in an Interesting Adult Sonic Hedgehog Mutated Medulloblastoma. Journal of Neuro-Oncology, 144, 231-233. https://doi.org/10.1007/s11060-019-03207-x
[35]
Largeaud, L., Berard, E., Bertoli, S., Dufrechou, S., Prade, N., Gadaud, N., et al. (2019) Outcome of AML Patients with IDH2 Mutations in Real World before the Era of IDH2 Inhibitors. Leukemia Research, 81, 82-87. https://doi.org/10.1016/j.leukres.2019.04.010
[36]
Pollyea, D.A., Tallman, M.S., de Botton, S., Kantarjian, H.M., Collins, R., Stein, A.S., et al. (2019) Enasidenib, an Inhibitor of Mutant IDH2 Proteins, Induces Durable Remissions in Older Patients with Newly Diagnosed Acute Myeloid Leukemia. Leukemia, 33, 2575-2584. https://doi.org/10.1038/s41375-019-0472-2
