{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T22:32:37Z","timestamp":1783031557550,"version":"3.54.6"},"reference-count":101,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The diagnostic and prognostic value of miRNAs in cutaneous melanoma (CM) has been broadly studied and supported by advanced bioinformatics tools. From early studies using miRNA arrays with several limitations, to the recent NGS-derived miRNA expression profiles, an accurate diagnostic panel of a comprehensive pre-specified set of miRNAs that could aid timely identification of specific cancer stages is still elusive, mainly because of the heterogeneity of the approaches and the samples. Herein, we summarize the existing studies that report several miRNAs as important diagnostic and prognostic biomarkers in CM. Using publicly available NGS data, we analyzed the correlation of specific miRNA expression profiles with the expression signatures of known gene targets. Combining network analytics with machine learning, we developed specific non-linear classification models that could successfully predict CM recurrence and metastasis, based on two newly identified miRNA signatures. Subsequent unbiased analyses and independent test sets (i.e., a dataset not used for training, as a validation cohort) using our prediction models resulted in 73.85% and 82.09% accuracy in predicting CM recurrence and metastasis, respectively. Overall, our approach combines detailed analysis of miRNA profiles with heuristic optimization and machine learning, which facilitates dimensionality reduction and optimization of the prediction models. Our approach provides an improved prediction strategy that could serve as an auxiliary tool towards precision treatment.<\/jats:p>","DOI":"10.3390\/ijms23031299","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T20:38:58Z","timestamp":1643143138000},"page":"1299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Revisiting miRNA Association with Melanoma Recurrence and Metastasis from a Machine Learning Point of View"],"prefix":"10.3390","volume":"23","author":[{"given":"Aigli","family":"Korfiati","sequence":"first","affiliation":[{"name":"Department of Medical Physics, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Grafanaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5628-6138","authenticated-orcid":false,"given":"George C.","family":"Kyriakopoulos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1188-529X","authenticated-orcid":false,"given":"Ilias","family":"Skeparnias","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Georgiou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Sakellaropoulos","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5699-4118","authenticated-orcid":false,"given":"Constantinos","family":"Stathopoulos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1080\/14737140.2018.1489246","article-title":"The eighth edition American Joint Committee on Cancer (AJCC) melanoma staging system: Implications for melanoma treatment and care","volume":"18","author":"Keung","year":"2018","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrc.2016.37","article-title":"From melanocytes to melanomas","volume":"16","author":"Shain","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2858","DOI":"10.1038\/s41467-020-15546-9","article-title":"Pre-clinical modeling of cutaneous melanoma","volume":"11","author":"Rebecca","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s11912-018-0732-8","article-title":"The World of Melanoma: Epidemiologic, Genetic, and Anatomic Differences of Melanoma Across the Globe","volume":"20","author":"Dimitriou","year":"2018","journal-title":"Curr. Oncol. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.immuni.2016.06.001","article-title":"Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and\u2014Extrinsic Factors","volume":"44","author":"Pitt","year":"2016","journal-title":"Immunity"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1016\/j.cell.2015.05.044","article-title":"Genomic Classification of Cutaneous Melanoma","volume":"161","author":"Akbani","year":"2015","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1016\/j.jid.2016.05.119","article-title":"Consensus of Melanoma Gene Expression Subtypes Converges on Biological Entities","volume":"136","author":"Lauss","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15790","DOI":"10.1038\/s41598-019-52134-4","article-title":"Prediction and Analysis of Skin Cancer Progression using Genomics Profiles of Patients","volume":"9","author":"Bhalla","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41467-019-14085-2","article-title":"Melanoblast transcriptome analysis reveals pathways promoting melanoma metastasis","volume":"11","author":"Marie","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Varrone, F., and Caputo, E. (2020). The miRNAs Role in Melanoma and in Its Resistance to Therapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030878"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ygeno.2016.04.005","article-title":"Integrated analysis of multidimensional omics data on cutaneous melanoma prognosis","volume":"107","author":"Jiang","year":"2016","journal-title":"Genomics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12703","DOI":"10.18632\/aging.103115","article-title":"Epigenomic and genomic analysis of transcriptome modulation in skin cutaneous melanoma","volume":"12","author":"Chen","year":"2020","journal-title":"Aging"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"BSR20201704","DOI":"10.1042\/BSR20201704","article-title":"Data mining of immune-related prognostic genes in metastatic melanoma microenvironment","volume":"40","author":"Han","year":"2020","journal-title":"Biosci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Meng, L., He, X., Zhang, X., Zhang, X., Wei, Y., Wu, B., Li, W., Li, J., and Xiao, Y. (2020). Predicting the clinical outcome of melanoma using an immune-related gene pairs signature. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0240331"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1158\/1541-7786.MCR-18-0173","article-title":"A Leukocyte Infiltration Score Defined by a Gene Signature Predicts Melanoma Patient Prognosis","volume":"17","author":"Zhao","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.18632\/aging.202279","article-title":"Exploration of the immune cell infiltration-related gene signature in the prognosis of melanoma","volume":"13","author":"Zeng","year":"2021","journal-title":"Aging"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"106921","DOI":"10.1016\/j.intimp.2020.106921","article-title":"An immune risk score with potential implications in prognosis and immunotherapy of metastatic melanoma","volume":"88","author":"Sheng","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Emran, A.A., Nsengimana, J., Punnia-Moorthy, G., Schmitz, U., Gallagher, S.J., Newton-Bishop, J., Tiffen, J.C., and Hersey, P. (2020). Study of the Female Sex Survival Advantage in Melanoma\u2014A Focus on X-Linked Epigenetic Regulators and Immune Responses in Two Cohorts. Cancers, 12.","DOI":"10.3390\/cancers12082082"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/s43018-020-0077-8","article-title":"Multi-omic analysis reveals significantly mutated genes and DDX3X as a sex-specific tumor suppressor in cutaneous melanoma","volume":"1","author":"Alkallas","year":"2020","journal-title":"Nat. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1021\/acs.jproteome.8b00110","article-title":"An Adaptive Pipeline to Maximize Isobaric Tagging Data in Large-Scale MS-Based Proteomics","volume":"17","author":"Theofilatos","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3389\/fcell.2020.00071","article-title":"miRNAs in the Diagnosis and Prognosis of Skin Cancer","volume":"8","author":"Neagu","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5133","DOI":"10.1002\/jcp.26395","article-title":"MicroRNAs in cutaneous melanoma: Role as diagnostic and prognostic biomarkers","volume":"233","author":"Ross","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mione, M., Liebig, J., Munoz, L., and Bosserhoff, A. (2017). MiRNAs in Malignant Melanoma. Melanoma Development, Springer International Publishing.","DOI":"10.1007\/978-3-319-41319-8_6"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.semcancer.2019.05.021","article-title":"MicroRNA heterogeneity in melanoma progression","volume":"59","author":"Thyagarajan","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"22262","DOI":"10.18632\/oncotarget.14763","article-title":"MicroRNAs in melanoma development and resistance to target therapy","volume":"8","author":"Fattore","year":"2017","journal-title":"Oncotarget"},{"key":"ref_26","first-page":"8987","article-title":"MicroRNA Signature in Melanoma: Biomarkers and Therapeutic Targets","volume":"11","author":"Gholipour","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lorusso, C., De Summa, S., Pinto, R., Danza, K., and Tommasi, S. (2020). miRNAs as Key Players in the Management of Cutaneous Melanoma. Cells, 9.","DOI":"10.3390\/cells9020415"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mumford, S., Towler, B., Pashler, A., Gilleard, O., Martin, Y., and Newbury, S. (2018). Circulating MicroRNA Biomarkers in Melanoma: Tools and Challenges in Personalised Medicine. Biomolecules, 8.","DOI":"10.3390\/biom8020021"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/pcmr.12544","article-title":"Metastatic pathways in patients with cutaneous melanoma","volume":"30","author":"Adler","year":"2017","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gajos-Michniewicz, A., and Czyz, M. (2019). Role of miRNAs in Melanoma Metastasis. Cancers, 11.","DOI":"10.3390\/cancers11030326"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bustos, M.A., Gross, R., Rahimzadeh, N., Cole, H., Tran, L.T., Tran, K.D., Takeshima, L., Stern, S.L., O\u2019Day, S., and Hoon, D.S.B. (2020). A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients. Cancers, 12.","DOI":"10.3390\/cancers12113361"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bustos, M.A., Tran, K.D., Rahimzadeh, N., Gross, R., Lin, S.Y., Shoji, Y., Murakami, T., Boley, C.L., Tran, L.T., and Cole, H. (2020). Integrated Assessment of Circulating Cell-Free MicroRNA Signatures in Plasma of Patients with Melanoma Brain Metastasis. Cancers, 12.","DOI":"10.3390\/cancers12061692"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/1878-0261.12669","article-title":"Pre-analytical factors affecting the establishment of a single tube assay for multiparameter liquid biopsy detection in melanoma patients","volume":"14","author":"Schneegans","year":"2020","journal-title":"Mol. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"289548","DOI":"10.1155\/2014\/289548","article-title":"Characterization of the Merkel Cell Carcinoma miRNome","volume":"2014","author":"Ning","year":"2014","journal-title":"J. Skin Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Meng, W., McElroy, J.P., Volinia, S., Palatini, J., Warner, S., Ayers, L.W., Palanichamy, K., Chakravarti, A., and Lautenschlaeger, T. (2013). Comparison of MicroRNA Deep Sequencing of Matched Formalin-Fixed Paraffin-Embedded and Fresh Frozen Cancer Tissues. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064393"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Babapoor, S., Fleming, E., Wu, R., and Dadras, S.S. (2014). A Novel miR-451a isomiR, Associated with Amelanotypic Phenotype, Acts as a Tumor Suppressor in Melanoma by Retarding Cell Migration and Invasion. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107502"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jid.2019.06.126","article-title":"MicroRNA Ratios Distinguish Melanomas from Nevi","volume":"140","author":"Torres","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_38","first-page":"197","article-title":"A preliminary study of microRNA expression in different types of primary melanoma","volume":"20","author":"Gencia","year":"2019","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1089\/cmb.2019.0198","article-title":"Novel MicroRNA Biomarkers, miR-142-5p, miR-550a, miR-1826, and miR-1201, Were Identified for Primary Melanoma","volume":"27","author":"Xu","year":"2020","journal-title":"J. Comput. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"100802","DOI":"10.1016\/j.tranon.2020.100802","article-title":"Distinguishing Tumor and Stromal Sources of MicroRNAs Linked to Metastasis in Cutaneous Melanoma","volume":"13","author":"Watt","year":"2020","journal-title":"Transl. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4903","DOI":"10.1158\/1078-0432.CCR-14-2566","article-title":"A miRNA-Based Signature Detected in Primary Melanoma Tissue Predicts Development of Brain Metastasis","volume":"21","author":"Hanniford","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_42","first-page":"9525","article-title":"MiR-155 inhibits proliferation, invasion and migration of melanoma via targeting CBL","volume":"23","author":"Li","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.1038\/s41598-020-61637-4","article-title":"Transcriptomic identification of miR-205 target genes potentially involved in metastasis and survival of cutaneous malignant melanoma","volume":"10","author":"Serna","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"84924","DOI":"10.18632\/oncotarget.12913","article-title":"Ultraviolet radiation-induced differential microRNA expression in the skin of hairless SKH1 mice, a widely used mouse model for dermatology research","volume":"7","author":"Singh","year":"2016","journal-title":"Oncotarget"},{"key":"ref_45","first-page":"13249","article-title":"Expression of miR-203 is decreased and associated with the prognosis of melanoma patients","volume":"8","author":"Wang","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.jid.2017.09.049","article-title":"Genome-Wide Screen for MicroRNAs Reveals a Role for miR-203 in Melanoma Metastasis","volume":"138","author":"Lohcharoenkal","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1002\/2211-5463.12819","article-title":"miR-21-5p promotes cell proliferation and G1\/S transition in melanoma by targeting CDKN2C","volume":"10","author":"Yang","year":"2020","journal-title":"FEBS Open Bio"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1158\/0008-5472.CAN-17-1318","article-title":"miR-204-5p and miR-211-5p Contribute to BRAF Inhibitor Resistance in Melanoma","volume":"78","author":"Alonso","year":"2018","journal-title":"Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Nyholm, A.M., Lerche, C.M., Manf\u00e9, V., Biskup, E., Johansen, P., Morling, N., Thomsen, B.M., Glud, M., and Gniadecki, R. (2014). miR-125b induces cellular senescence in malignant melanoma. BMC Dermatol., 14.","DOI":"10.1186\/1471-5945-14-8"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3727\/096504018X15228863026239","article-title":"miR-150 Suppresses Tumor Growth in Melanoma Through Downregulation of MYB","volume":"27","author":"Sun","year":"2019","journal-title":"Oncol. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17076","DOI":"10.1038\/s41598-018-35317-3","article-title":"Downregulation of intratumoral expression of miR-205, miR-200c and miR-125b in primary human cutaneous melanomas predicts shorter survival","volume":"8","author":"Murgui","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_52","first-page":"28","article-title":"A panel of miRNAs as prognostic indicators for clinical outcome of skin cutaneous melanoma","volume":"9","author":"Guo","year":"2016","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ebiom.2015.05.011","article-title":"The Prognostic and Predictive Value of Melanoma-related MicroRNAs Using Tissue and Serum: A MicroRNA Expression Analysis","volume":"2","author":"Stark","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1158\/1078-0432.CCR-09-2721","article-title":"Melanoma MicroRNA Signature Predicts Post-Recurrence Survival","volume":"16","author":"Segura","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e7831","DOI":"10.7717\/peerj.7831","article-title":"Identification of a five-miRNA signature predicting survival in cutaneous melanoma cancer patients","volume":"7","author":"Lu","year":"2019","journal-title":"PeerJ"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/modpathol.2015.149","article-title":"microRNA-10b is a prognostic biomarker for melanoma","volume":"29","author":"Saldanha","year":"2016","journal-title":"Mod. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1038\/jid.2010.63","article-title":"MicroRNA Expression Profiles Associated with Mutational Status and Survival in Malignant Melanoma","volume":"130","author":"Caramuta","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/pcmr.12343","article-title":"MicroRNA and mRNA expression profiling in metastatic melanoma reveal associations with BRAF mutation and patient prognosis","volume":"28","author":"Tembe","year":"2015","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/labinvest.2017.5","article-title":"Identification of microRNAs associated with invasive and aggressive phenotype in cutaneous melanoma by next-generation sequencing","volume":"97","author":"Babapoor","year":"2017","journal-title":"Lab. Investig."},{"key":"ref_60","first-page":"5243","article-title":"Identification of prognostic biomarkers for malignant melanoma using microarray datasets","volume":"18","author":"Lin","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_61","first-page":"6066","article-title":"Prognostic genes of melanoma identified by weighted gene co-expression network analysis and drug repositioning using a network-based method","volume":"18","author":"Wang","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1097\/CMR.0000000000000697","article-title":"Identification of prognostic mRNAs in metastatic cutaneous melanoma","volume":"30","author":"Lee","year":"2020","journal-title":"Melanoma Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e26017","DOI":"10.1097\/MD.0000000000026017","article-title":"Identification of prognostic genes and construction of a novel gene signature in the skin melanoma based on the tumor microenvironment","volume":"100","author":"Yingjuan","year":"2021","journal-title":"Medicine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9874","DOI":"10.3389\/fonc.2021.639874","article-title":"A Four-Gene-Based Prognostic Model Predicts Overall Survival in Patients with Cutaneous Melanoma","volume":"11","author":"Tong","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Yang, L., Xu, Y., Yan, Y., Luo, P., Chen, S., Zheng, B., Yan, W., Chen, Y., and Wang, C. (2019). Common Nevus and Skin Cutaneous Melanoma: Prognostic Genes Identified by Gene Co-Expression Network Analysis. Genes, 10.","DOI":"10.3390\/genes10100747"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00432-012-1322-z","article-title":"A nine-gene signature predicting clinical outcome in cutaneous melanoma","volume":"139","author":"Brunner","year":"2013","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1158\/1078-0432.CCR-13-3316","article-title":"Development of a Prognostic Genetic Signature to Predict the Metastatic Risk Associated with Cutaneous Melanoma","volume":"21","author":"Gerami","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"11613","DOI":"10.1111\/jcmm.15822","article-title":"Screening and identification of potential prognostic biomarkers in metastatic skin cutaneous melanoma by bioinformatics analysis","volume":"24","author":"Sheng","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"17314","DOI":"10.1038\/s41598-017-17330-0","article-title":"Identification of a gene signature for discriminating metastatic from primary melanoma using a molecular interaction network approach","volume":"7","author":"Metri","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7424","DOI":"10.1158\/1078-0432.CCR-18-3659","article-title":"Transcriptomic Analysis Reveals Prognostic Molecular Signatures of Stage I Melanoma","volume":"25","author":"Thakur","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_71","first-page":"2161","article-title":"A four-gene expression-based signature predicts the clinical outcome of melanoma","volume":"24","author":"Sun","year":"2019","journal-title":"J. BUON"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Wan, Q., Liu, C., Liu, C., Liu, W., Wang, X., and Wang, Z. (2020). Discovery and Validation of a Metastasis-Related Prognostic and Diagnostic Biomarker for Melanoma Based on Single Cell and Gene Expression Datasets. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.585980"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5323614","DOI":"10.1155\/2020\/5323614","article-title":"Identification and Validation of Prognostically Relevant Gene Signature in Melanoma","volume":"2020","author":"Gao","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.12659\/MSM.913881","article-title":"Integrative Analysis of Long Noncoding RNA (lncRNA), microRNA (miRNA) and mRNA Expression and Construction of a Competing Endogenous RNA (ceRNA) Network in Metastatic Melanoma","volume":"25","author":"Wang","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"143","DOI":"10.21873\/anticanres.11299","article-title":"Potential Prognostic Molecular Signatures in a Preclinical Model of Melanoma","volume":"37","author":"Fortis","year":"2017","journal-title":"Anticancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.neo.2021.03.007","article-title":"Transcriptional signatures underlying dynamic phenotypic switching and novel disease biomarkers in a linear cellular model of melanoma progression","volume":"23","author":"Rius","year":"2021","journal-title":"Neoplasia"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/s41591-020-0818-3","article-title":"Multimodel preclinical platform predicts clinical response of melanoma to immunotherapy","volume":"26","author":"Yang","year":"2020","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/JID.2015.355","article-title":"Identification, Review, and Systematic Cross-Validation of microRNA Prognostic Signatures in Metastatic Melanoma","volume":"136","author":"Jayawardana","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Xiong, J., Bing, Z., and Guo, S. (2019). Observed Survival Interval: A Supplement to TCGA Pan-Cancer Clinical Data Resource. Cancers, 11.","DOI":"10.3390\/cancers11030280"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"165","DOI":"10.4161\/auto.8.2.18351","article-title":"miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1","volume":"8","author":"Korkmaz","year":"2012","journal-title":"Autophagy"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.yexmp.2018.11.001","article-title":"MicroRNA-sequencing data analyzing melanoma development and progression","volume":"105","author":"Linck","year":"2018","journal-title":"Exp. Mol. Pathol."},{"key":"ref_82","first-page":"61","article-title":"miR-1226 targets expression of the mucin 1 oncoprotein and induces cell death","volume":"37","author":"Jin","year":"2010","journal-title":"Int. J. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Yang, L., Du, X., Liu, L., Cao, Q., Pan, Z., and Li, Q. (2019). miR-1306 Mediates the Feedback Regulation of the TGF-\u03b2\/SMAD Signaling Pathway in Granulosa Cells. Cells, 8.","DOI":"10.3390\/cells8040298"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1002\/cam4.1315","article-title":"Integrative analysis of competing endogenous RNA network focusing on long noncoding RNA associated with progression of cutaneous melanoma","volume":"7","author":"Xu","year":"2018","journal-title":"Cancer Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1515\/hsz-2019-0407","article-title":"Hsa-miR-186-5p regulates TGF\u03b2 signaling pathway through expression suppression of SMAD6 and SMAD7 genes in colorectal cancer","volume":"402","author":"Bayat","year":"2021","journal-title":"Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"60","DOI":"10.4103\/0973-1482.157340","article-title":"MiR-186 inhibits cell proliferation and invasion in human cutaneous malignant melanoma","volume":"14","author":"Su","year":"2018","journal-title":"J. Cancer Res. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4972","DOI":"10.1158\/0008-5472.CAN-20-1162","article-title":"A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking","volume":"80","author":"Harrison","year":"2020","journal-title":"Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"148","DOI":"10.14715\/cmb\/2020.66.5.26","article-title":"Guizhi Fuling pills inhibit the proliferation, migration and invasion of human cutaneous malignant melanoma cells by regulating the molecular axis of LncRNA TPT1-AS1\/miR-671-5p","volume":"66","author":"Zhang","year":"2020","journal-title":"Cell. Mol. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"144648","DOI":"10.1016\/j.gene.2020.144648","article-title":"Association of miR-760 with cancer: An overview","volume":"747","author":"Manvati","year":"2020","journal-title":"Gene"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.2147\/OTT.S290567","article-title":"miR-944 Suppresses EGF-Induced EMT in Colorectal Cancer Cells by Directly Targeting GATA6","volume":"14","author":"Tang","year":"2021","journal-title":"OncoTargets Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.2147\/CMAR.S199818","article-title":"microRNA-944 inhibits the malignancy of hepatocellular carcinoma by directly targeting IGF-1R and deactivating the PI3K\/Akt signaling pathway","volume":"11","author":"Lv","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Park, S., Kim, J., Eom, K., Oh, S., Kim, S., Kim, G., Ahn, S., Park, K.H., Chung, D., and Lee, H. (2019). microRNA-944 overexpression is a biomarker for poor prognosis of advanced cervical cancer. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5620-6"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.bbrc.2016.04.030","article-title":"MicroRNA-1976 functions as a tumor suppressor and serves as a prognostic indicator in non-small cell lung cancer by directly targeting PLCE1","volume":"473","author":"Chen","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/s41419-020-2711-x","article-title":"MiR-1976 knockdown promotes epithelial\u2013mesenchymal transition and cancer stem cell properties inducing triple-negative breast cancer metastasis","volume":"11","author":"Wang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1089\/omi.2018.0048","article-title":"Drug Targeting and Biomarkers in Head and Neck Cancers: Insights from Systems Biology Analyses","volume":"22","author":"Islam","year":"2018","journal-title":"Omics J. Integr. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"030006052098154","DOI":"10.1177\/0300060520981547","article-title":"Expression and clinical significance of miR-3615 in hepatocellular carcinoma","volume":"49","author":"Yuan","year":"2021","journal-title":"J. Int. Med. Res."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Theofilatos, K., Korfiati, A., Mavroudi, S., Cowperthwaite, M.C., and Shpak, M. (2019). Discovery of stroke-related blood biomarkers from gene expression network models. BMC Med. Genom., 12.","DOI":"10.1186\/s12920-019-0566-8"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1097\/CMR.0b013e328363e485","article-title":"Sensitive detection of melanoma metastasis using circulating microRNA expression profiles","volume":"23","author":"Shiiyama","year":"2013","journal-title":"Melanoma Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jid.2019.07.688","article-title":"Human against Machine? Machine Learning Identifies MicroRNA Ratios as Biomarkers for Melanoma","volume":"140","author":"Shellman","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ejca.2021.02.032","article-title":"Combining CNN-based histologic whole slide image analysis and patient data to improve skin cancer classification","volume":"149","author":"Jutzi","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/s41419-019-2048-5","article-title":"Single cell analysis to dissect molecular heterogeneity and disease evolution in metastatic melanoma","volume":"10","author":"Fattore","year":"2019","journal-title":"Cell Death Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1299\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:06:52Z","timestamp":1760134012000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,24]]},"references-count":101,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23031299"],"URL":"https:\/\/doi.org\/10.3390\/ijms23031299","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,24]]}}}