Skip to main content

Advertisement

SpringerLink
Log in

Promising Blood-Based Biomarkers for Melanoma: Recent Progress of Liquid Biopsy and Its Future Perspectives

  • Skin Cancer (T Ito, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Because the recent success of novel therapeutic approaches has dramatically changed the clinical management of melanoma, less invasive and repeatable monitoring tools that can predict the disease status, drug resistance, and the development of side effects are increasingly needed. As liquid biopsy has enabled us to diagnose and monitor disease status less invasively, substantial attention has been directed toward this technique, which is gaining importance as a diagnostic and/or prognostic tool. It is evident that microRNA, cell-free DNA, and circulating tumor cells obtained via liquid biopsy are promising diagnostic and prognostic tools for melanoma, and they also have utility for monitoring the disease status and predicting drug effects. Although current challenges exist for each biomarker, such as poor sensitivity and/or specificity and technical problems, recent technical advances have increasingly improved these aspects. For example, next-generation sequencing technology for detecting microRNAs or cell-free DNA enabled high-throughput analysis and provided significantly higher sensitivity. In particular, cancer personalized profiling by deep sequencing for quantifying cell-free DNA is a promising method for high-throughput analysis that provides real-time comprehensive data for patients at various disease stages. For wide clinical implementation, it is necessary to increase the sensitivity for the markers and standardize the assay procedures to make them reproducible, valid, and inexpensive; however, the broad clinical application of liquid biopsy could occur quickly. This review focuses on the significance of liquid biopsy, particularly related to the use of blood samples from patients with melanoma, and discusses its future perspectives.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Arozarena I, Wellbrock C. Overcoming resistance to BRAF inhibitors. Ann Transl Med. 2017;5(19):387.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Boyer M, Cayrefourcq L, Dereure O, Meunier L, Becquart O, Alix-Panabières C. Clinical relevance of liquid biopsy in melanoma and Merkel cell carcinoma. Cancers. 2020;12(4):960.

    Article  CAS  PubMed Central  Google Scholar 

  3. Wakamatsu K, Fukushima S, Minagawa A, Omodaka T, Hida T, Hatta N, Takata M, Uhara H, Okuyama R, Ihn H. Significance of 5-S-cysteinyldopa as a marker for melanoma. Int J Mol Sci. 2020;21(2):432.

    Article  CAS  PubMed Central  Google Scholar 

  4. Huang SK, Hoon DS. Liquid biopsy utility for the surveillance of cutaneous malignant melanoma patients. Mol Oncol. 2016;10(3):450–63.

    Article  PubMed  Google Scholar 

  5. Ikuta Y, Nakatsura T, Kageshita T, Fukushima S, Ito S, Wakamatsu K, Baba H, Nishimura Y. Highly sensitive detection of melanoma at an early stage based on the increased serum secreted protein acidic and rich in cysteine and glypican-3 levels. Clin Cancer Res. 2005;11(22):8079–88.

    Article  CAS  PubMed  Google Scholar 

  6. Mouawad R, Spano J, Khayat D. Old and new serological biomarkers in melanoma: where we are in 2009. Melanoma Res. 2010;20(2):67–76.

    Article  PubMed  Google Scholar 

  7. Jain KK. Cancer biomarkers: current issues and future directions. Curr Opin Mol Ther. 2007;9(6):563–71.

    CAS  PubMed  Google Scholar 

  8. Calin G, Croce C. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.

    Article  CAS  PubMed  Google Scholar 

  9. Esquela-Kerscher A, Slack F. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69.

    Article  CAS  PubMed  Google Scholar 

  10. Mitchell P, Parkin R, Kroh E, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105(30):10513–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kanemaru H, Fukushima S, Yamashita J, Honda N, Oyama R, Kakimoto A, Masuguchi S, Ishihara T, Inoue Y, Jinnin M, Ihn H. The circulating microRNA-221 level in patients with malignant melanoma as a new tumor marker. J Dermatol Sci. 2011;61(3):187–93.

    Article  CAS  PubMed  Google Scholar 

  12. Li P, He QY, Luo CQ, Qian LY. Circulating miR-221 expression level and prognosis of cutaneous malignant melanoma. Med Sci Monit. 2014;20:2472–7.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Saldanha G, Potter L, Shendge P, Osborne J, Nicholson S, Yii NW, Varma S, Aslam MI, Elshaw S, Papadogeorgakis E, Howard Pringle J. Plasma microRNA-21 is associated with tumor burden in cutaneous melanoma. J Invest Dermatol. 2013;133(5):1381–4.

    Article  CAS  PubMed  Google Scholar 

  14. Xu SJ, Xu WJ, Zeng Z, et al. MiR-424 functions as potential diagnostic and prognostic biomarker in melanoma. Clin Lab. 2020;66(7) https://doi.org/10.7754/Clin.Lab.2019.190917.

  15. Margue C, Reinsbach S, Philippidou D, Beaume N, Walters C, Schneider JG, Nashan D, Behrmann I, Kreis S. Comparison of a healthy miRNome with melanoma patient miRNomes: are microRNAs suitable serum biomarkers for cancer? Oncotarget. 2015;6(14):12110–27.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sahranavardfard P, Firouzi J, Azimi M, Khosravani P, Heydari R, Emami Razavi A, Dorraj M, Keighobadi F, Ebrahimi M. MicroRNA-203 reinforces stemness properties in melanoma and augments tumorigenesis in vivo. J Cell Physiol. 2019;234(11):20193–205.

    Article  CAS  PubMed  Google Scholar 

  17. Bai M, Zhang H, Si L, Yu N, Zeng A, Zhao R. Upregulation of serum miR-10b is associated with poor prognosis in patients with melanoma. J Cancer. 2017;8(13):2487–91.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ono S, Oyama T, Lam S, Chong K, Foshag LJ, Hoon DSB. A direct plasma assay of circulating microRNA-210 of hypoxia can identify early systemic metastasis recurrence in melanoma patients. Oncotarget. 2015;6(9):7053–64.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tengda L, Shuping L, Mingli G, Jie G, Yun L, Weiwei Z, Anmei D. Serum exosomal microRNAs as potent circulating biomarkers for melanoma. Melanoma Res. 2018;28(4):295–303.

    Article  PubMed  Google Scholar 

  20. Tembe V, Schramm SJ, Stark MS, Patrick E, Jayaswal V, Tang YH, Barbour A, Hayward NK, Thompson JF, Scolyer RA, Yang YH, Mann GJ. MicroRNA and mRNA expression profiling in metastatic melanoma reveal associations with BRAF mutation and patient prognosis. Pigment Cell Melanoma Res. 2015;28(3):254–66.

    Article  CAS  PubMed  Google Scholar 

  21. Greenberg E, Besser MJ, Ben-Ami E, Shapira-Frommer R, Itzhaki O, Zikich D, Levy D, Kubi A, Eyal E, Onn A, Cohen Y, Barshack I, Schachter J, Markel G. A comparative analysis of total serum miRNA profiles identifies novel signature that is highly indicative of metastatic melanoma: a pilot study. Biomarkers. 2013;18(6):502–8.

    Article  CAS  PubMed  Google Scholar 

  22. Solé C, Tramonti D, Schramm M, Goicoechea I, Armesto M, Hernandez L, Manterola L, Fernandez-Mercado M, Mujika K, Tuneu A, Jaka A, Tellaetxe M, Friedländer M, Estivill X, Piazza P, Ortiz-Romero P, Middleton M, Lawrie C. The circulating transcriptome as a source of biomarkers for melanoma. Cancers. 2019;11(1):70.

    Article  PubMed Central  Google Scholar 

  23. Fogli S, Polini B, Carpi S, Pardini B, Naccarati A, Dubbini N, Lanza M, Breschi MC, Romanini A, Nieri P. Identification of plasma microRNAs as new potential biomarkers with high diagnostic power in human cutaneous melanoma. Tumour Biol. 2017;39(5):1010428317701646.

    Article  PubMed  Google Scholar 

  24. Tian R, Liu T, Qiao L, Gao M, Li J. Decreased serum microRNA-206 level predicts unfavorable prognosis in patients with melanoma. Int J Clin Exp Pathol. 2015;8(3):3097–103.

    PubMed  PubMed Central  Google Scholar 

  25. Van Laar R, Lincoln M, Van Laar B. Development and validation of a plasma-based melanoma biomarker suitable for clinical use. Br J Cancer. 2018;118(6):857–66.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Guo W, Wang H, Yang Y, Guo S, Zhang W, Liu Y, Yi X, Ma J, Zhao T, Liu L, Jian Z, Liu L, Wang G, Gao T, Shi Q, Li C. Down-regulated miR-23a contributes to the metastasis of cutaneous melanoma by promoting autophagy. Theranostics. 2017;7(8):2231–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Leidinger P, Keller A, Borries A, Reichrath J, Rass K, Jager SU, Lenhof HP, Meese E. High-throughput miRNA profiling of human melanoma blood samples. BMC Cancer. 2010;10:262.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Shiiyama R, Fukushima S, Jinnin M, Yamashita J, Miyashita A, Nakahara S, Kogi A, Aoi J, Masuguchi S, Inoue Y, Ihn H. Sensitive detection of melanoma metastasis using circulating microRNA expression profiles. Melanoma Res. 2013;23(5):366–72.

    Article  CAS  PubMed  Google Scholar 

  29. Fleming NH, Zhong J, da Silva IP, Vega-Saenz de Miera E, Brady B, Han SW, Hanniford D, Wang J, Shapiro RL, Hernando E, Osman I. Serum-based miRNAs in the prediction and detection of recurrence in melanoma patients. Cancer. 2015;121(1):51–9.

    Article  CAS  PubMed  Google Scholar 

  30. Armand-Labit V, Meyer N, Casanova A, Bonnabau H, Platzer V, Tournier E, Sansas B, Verdun S, Thouvenot B, Hilselberger B, Doncescu A, Lamant L, Lacroix-Triki M, Favre G, Pradines A. Identification of a circulating microRNA profile as a biomarker of metastatic cutaneous melanoma. Acta Derm Venereol. 2016;96(1):29–34.

    Article  CAS  PubMed  Google Scholar 

  31. Friedman EB, Shang S, de Miera EV, et al. Serum microRNAs as biomarkers for recurrence in melanoma. J Transl Med. 2012;10:155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Stark MS, Klein K, Weide B, Haydu LE, Pflugfelder A, Tang YH, Palmer JM, Whiteman DC, Scolyer RA, Mann GJ, Thompson JF, Long GV, Barbour AP, Soyer HP, Garbe C, Herington A, Pollock PM, Hayward NK. The prognostic and predictive value of melanoma-related microRNAs using tissue and serum: a microRNA expression analysis. EBioMedicine. 2015;2(7):671–80.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Nakahara S, Fukushima S, Okada E, Morinaga J, Kubo Y, Tokuzumi A, Matsumoto S, Tsuruta-Kadohisa M, Kimura T, Kuriyama H, Miyashita A, Kajihara I, Jinnin M, Ihn H. MicroRNAs that predict the effectiveness of anti-PD-1 therapies in patients with advanced melanoma. J Dermatol Sci. 2020;97(1):77–9.

    Article  CAS  PubMed  Google Scholar 

  34. Bustos MA, Gross R, Rahimzadeh N, Cole H, Tran LT, Tran KD, Takeshima L, Stern SL, O’Day S, Hoon DSB. 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. 2020;12(11):3361.

    Article  CAS  PubMed Central  Google Scholar 

  35. Bustos MA, Tran KD, Rahimzadeh N, Gross R, Lin SY, Shoji Y, Murakami T, Boley CL, Tran LT, Cole H, Kelly DF, O’Day S, Hoon DSB. Integrated assessment of circulating cell-free microRNA signatures in plasma of patients with melanoma brain metastasis. Cancers. 2020;12(6):1692.

    Article  CAS  PubMed Central  Google Scholar 

  36. Ragusa M, Barbagallo C, Statello L, Caltabiano R, Russo A, Puzzo L, Avitabile T, Longo A, Toro MD, Barbagallo D, Valadi H, di Pietro C, Purrello M, Reibaldi M. miRNA profiling in vitreous humor, vitreal exosomes and serum from uveal melanoma patients: pathological and diagnostic implications. Cancer Biol Ther. 2015;16(9):1387–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Stark MS, Gray ES, Isaacs T, Chen FK, Millward M, McEvoy A, Zaenker P, Ziman M, Soyer HP, Glasson WJ, Warrier SK, Stark AL, Rolfe OJ, Palmer JM, Hayward NK. A panel of circulating microRNAs detects uveal melanoma with high precision. Transl Vis Sci Technol. 2019;8(6):12.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Cui M, Wang H, Yao X, Zhang D, Xie Y, Cui R, Zhang X. Circulating microRNAs in cancer: potential and challenge. Front Genet. 2019;10:626.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. •• Carpi S, Polini B, Fogli S, Podestà A, Ylösmäki E, Cerullo V, Romanini A, Nieri P. Circulating microRNAs as biomarkers for early diagnosis of cutaneous melanoma. Expert Rev Mol Diagn. 2020;20(1):19–30. This review has summarized the previously reported circulating miRNAs as biomarkers for early diagnosis of melanoma

    Article  CAS  PubMed  Google Scholar 

  40. •• Sacco A, Forgione L, Carotenuto M, de Luca A, Ascierto PA, Botti G, Normanno N. Circulating tumor DNA testing opens new perspectives in melanoma management. Cancers. 2020;12(10):2914. This review has summarized the application of cell free DNA from melanoma patients

    Article  CAS  PubMed Central  Google Scholar 

  41. Cabel L, Proudhon C, Romano E, Girard N, Lantz O, Stern MH, Pierga JY, Bidard FC. Clinical potential of circulating tumour DNA in patients receiving anticancer immunotherapy. Nat Rev Clin Oncol. 2018;15(10):639–50.

    Article  CAS  PubMed  Google Scholar 

  42. Calapre L, Warburton L, Millward M, Ziman M, Gray ES. Circulating tumour DNA (ctDNA) as a liquid biopsy for melanoma. Cancer Lett. 2017;404:62–9.

    Article  CAS  PubMed  Google Scholar 

  43. Dawson SJ, Tsui DW, Murtaza M, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368(13):1199–209.

    Article  CAS  PubMed  Google Scholar 

  44. Crowley E, Di Nicolantonio F, Loupakis F, et al. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol. 2013;10(8):472–84.

    Article  CAS  PubMed  Google Scholar 

  45. Gray ES, Rizos H, Reid AL, Boyd SC, Pereira MR, Lo J, Tembe V, Freeman J, Lee JHJ, Scolyer RA, Siew K, Lomma C, Cooper A, Khattak MA, Meniawy TM, Long GV, Carlino MS, Millward M, Ziman M. Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma. Oncotarget. 2015;6(39):42008–18.

    Article  PubMed  Google Scholar 

  46. Cheng F, Su L, Qian C. Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer. Oncotarget. 2016;7(30):48832–41.

    Article  PubMed  Google Scholar 

  47. Newman AM, Bratman SV, To J, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014;20(5):548–54.

    Article  CAS  PubMed  Google Scholar 

  48. Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Thornton K, Agrawal N, Sokoll L, Szabo SA, Kinzler KW, Vogelstein B, Diaz Jr LA. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008;14(9):985–90.

    Article  CAS  PubMed  Google Scholar 

  49. Iwahashi N, Sakai K, Noguchi T, Yahata T, Matsukawa H, Toujima S, Nishio K, Ino K. Liquid biopsy-based comprehensive gene mutation profiling for gynecological cancer using CAncer Personalized Profiling by deep Sequencing. Sci Rep. 2019;9(1):10426.

    Article  PubMed  Google Scholar 

  50. Ascierto PA, Minor D, Ribas A, Lebbe C, O'Hagan A, Arya N, Guckert M, Schadendorf D, Kefford RF, Grob JJ, Hamid O, Amaravadi R, Simeone E, Wilhelm T, Kim KB, Long GV, Martin AM, Mazumdar J, Goodman VL, Trefzer U. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol. 2013;31(26):3205–11.

    Article  CAS  PubMed  Google Scholar 

  51. Sanmamed MF, Fernandez-Landazuri S, Rodriguez C, et al. Quantitative cell-free circulating BRAFV600E mutation analysis by use of droplet digital PCR in the follow-up of patients with melanoma being treated with BRAF inhibitors. Clin Chem. 2015;61(1):297–304.

    Article  CAS  PubMed  Google Scholar 

  52. Emelyanova MA, Telysheva EN, Orlova KV, Ryabaya OO, Snigiryova GP, Abramov IS, Mikhailovich VM. Microarray-based analysis of the BRAF V600 mutations in circulating tumor DNA in melanoma patients. Cancer Genet. 2021;250–251:25–35.

    Article  PubMed  Google Scholar 

  53. Gonzalez-Cao M, Mayo-de-Las-Casas C, Molina-Vila MA, et al. BRAF mutation analysis in circulating free tumor DNA of melanoma patients treated with BRAF inhibitors. Melanoma Res. 2015;25(6):486–95.

    Article  CAS  PubMed  Google Scholar 

  54. Knol AC, Vallée A, Herbreteau G, Nguyen JM, Varey E, Gaultier A, Théoleyre S, Saint-Jean M, Peuvrel L, Brocard A, Quéreux G, Khammari A, Denis MG, Dréno B. Clinical significance of BRAF mutation status in circulating tumor DNA of metastatic melanoma patients at baseline. Exp Dermatol. 2016;25(10):783–8.

    Article  CAS  PubMed  Google Scholar 

  55. Marczynski GT, Laus AC, Dos Reis MB, et al. Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients. Sci Rep. 2020;10(1):18682.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Seremet T, Jansen Y, Planken S, Njimi H, Delaunoy M, el Housni H, Awada G, Schwarze JK, Keyaerts M, Everaert H, Lienard D, del Marmol V, Heimann P, Neyns B. Undetectable circulating tumor DNA (ctDNA) levels correlate with favorable outcome in metastatic melanoma patients treated with anti-PD1 therapy. J Transl Med. 2019;17(1):303.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Váraljai R, Elouali S, Lueong SS, Wistuba-Hamprecht K, Seremet T, Siveke JT, Becker JC, Sucker A, Paschen A, Horn PA, Neyns B, Weide B, Schadendorf D, Roesch A. The predictive and prognostic significance of cell-free DNA concentration in melanoma. J Eur Acad Dermatol Venereol. 2021;35(2):387–95.

    Article  PubMed  Google Scholar 

  58. Chang GA, Tadepalli JS, Shao Y, Zhang Y, Weiss S, Robinson E, Spittle C, Furtado M, Shelton DN, Karlin-Neumann G, Pavlick A, Osman I, Polsky D. Sensitivity of plasma BRAFmutant and NRASmutant cell-free DNA assays to detect metastatic melanoma in patients with low RECIST scores and non-RECIST disease progression. Mol Oncol. 2016;10(1):157–65.

    Article  CAS  PubMed  Google Scholar 

  59. Ashida A, Sakaizawa K, Mikoshiba A, Uhara H, Okuyama R. Quantitative analysis of the BRAF (V600E) mutation in circulating tumor-derived DNA in melanoma patients using competitive allele-specific TaqMan PCR. Int J Clin Oncol. 2016;21(5):981–8.

    Article  CAS  PubMed  Google Scholar 

  60. Knuever J, Weiss J, Persa OD, Kreuzer K, Mauch C, Hallek M, Schlaak M. The use of circulating cell-free tumor DNA in routine diagnostics of metastatic melanoma patients. Sci Rep. 2020;10(1):4940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Schreuer M, Meersseman G, Van Den Herrewegen S, et al. Quantitative assessment of BRAF V600 mutant circulating cell-free tumor DNA as a tool for therapeutic monitoring in metastatic melanoma patients treated with BRAF/MEK inhibitors. J Transl Med. 2016;14:95.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Di Guardo L, Randon G, Corti F, et al. Liquid biopsy and radiological response predict outcomes following discontinuation of targeted therapy in patients with BRAF mutated melanoma. Oncologist. 2021;in press;26:1079–84.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Herbreteau G, Vallée A, Knol AC, Théoleyre S, Quéreux G, Varey E, Khammari A, Dréno B, Denis MG. Quantitative monitoring of circulating tumor DNA predicts response of cutaneous metastatic melanoma to anti-PD1 immunotherapy. Oncotarget. 2018;9(38):25265–76.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Forthun RB, Hovland R, Schuster C, et al. ctDNA detected by ddPCR reveals changes in tumour load in metastatic malignant melanoma treated with bevacizumab. Sci Rep. 2019;9(1):17471.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Tsao SC, Weiss J, Hudson C, et al. Monitoring response to therapy in melanoma by quantifying circulating tumour DNA with droplet digital PCR for BRAF and NRAS mutations. Sci Rep. 2015;5:11198.

    Article  PubMed  Google Scholar 

  66. Lee RJ, Gremel G, Marshall A, Myers KA, Fisher N, Dunn JA, Dhomen N, Corrie PG, Middleton MR, Lorigan P, Marais R. Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma. Ann Oncol. 2018;29(2):490–6.

    Article  CAS  PubMed  Google Scholar 

  67. Long-Mira E, Ilie M, Chamorey E, Leduff-Blanc F, Montaudié H, Tanga V, Allégra M, Lespinet-Fabre V, Bordone O, Bonnetaud C, Schiappa R, Butori C, Bence C, Lacour JP, Hofman V, Hofman P. Monitoring BRAF and NRAS mutations with cell-free circulating tumor DNA from metastatic melanoma patients. Oncotarget. 2018;9(90):36238–49.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Lipson EJ, Velculescu VE, Pritchard TS, Sausen M, Pardoll DM, Topalian SL, Diaz LA. Circulating tumor DNA analysis as a real-time method for monitoring tumor burden in melanoma patients undergoing treatment with immune checkpoint blockade. J Immunother Cancer. 2014;2(1):42.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Girotti MR, Gremel G, Lee R, Galvani E, Rothwell D, Viros A, Mandal AK, Lim KHJ, Saturno G, Furney SJ, Baenke F, Pedersen M, Rogan J, Swan J, Smith M, Fusi A, Oudit D, Dhomen N, Brady G, et al. Application of sequencing, liquid biopsies, and patient-derived xenografts for personalized medicine in melanoma. Cancer Discov. 2016;6(3):286–99.

    Article  CAS  PubMed  Google Scholar 

  70. Lin SY, Huang SK, Huynh KT, et al. Multiplex gene profiling of cell-free DNA in patients with metastatic melanoma for monitoring disease. JCO Precis Oncol. 2018;2 PO.17.00225

  71. Forschner A, Battke F, Hadaschik D, Schulze M, Weißgraeber S, Han CT, Kopp M, Frick M, Klumpp B, Tietze N, Amaral T, Martus P, Sinnberg T, Eigentler T, Keim U, Garbe C, Döcker D, Biskup S. Tumor mutation burden and circulating tumor DNA in combined CTLA-4 and PD-1 antibody therapy in metastatic melanoma - results of a prospective biomarker study. J Immunother Cancer. 2019;7(1):180.

    Article  PubMed  PubMed Central  Google Scholar 

  72. • Diefenbach RJ, Lee JH, Menzies AM, Carlino MS, Long GV, Saw RPM, Howle JR, Spillane AJ, Scolyer RA, Kefford RF, Rizos H. Design and testing of a custom melanoma next generation sequencing panel for analysis of circulating tumor DNA. Cancers. 2020;12(8):2228. This paper has shown comprehensive cfDNA analysis of melanoma using a next-generation sequencing panel based on 30 genes covering driver and targetable mutations

    Article  CAS  PubMed Central  Google Scholar 

  73. Olbryt M, Rajczykowski M, Bal W, Fiszer-Kierzkowska A, Cortez AJ, Mazur M, Suwiński R, Widłak W. NGS analysis of liquid biopsy (LB) and formalin-fixed paraffin-embedded (FFPE) melanoma samples using Oncomine™ Pan-Cancer Cell-Free Assay. Genes (Basel). 2021;12(7):1080.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Gangadhar TC, Savitch SL, Yee SS, Xu W, Huang AC, Harmon S, Lieberman DB, Soucier D, Fan R, Black TA, Morrissette JJD, Salathia N, Waters J, Zhang S, Toung J, van Hummelen P, Fan JB, Xu X, Amaravadi RK, et al. Feasibility of monitoring advanced melanoma patients using cell-free DNA from plasma. Pigment Cell Melanoma Res. 2018;31(1):73–81.

    Article  CAS  PubMed  Google Scholar 

  75. • Kaneko A, Kanemaru H, Kajihara I, Mijiddorj T, Miyauchi H, Kuriyama H, Kimura T, Sawamura S, Makino K, Miyashita A, Aoi J, Makino T, Masuguchi S, Fukushima S, Ihn H. Liquid biopsy-based analysis by ddPCR and CAPP-Seq in melanoma patients. J Dermatol Sci. 2021;102(3):158–66. This paper has shown the utility of CAPP-Seq analyses in melanoma patients and suggested that MET may be a promising biomarker to monitor the disease status in melanoma patients when treated with BRAF/MEK inhibitor

    Article  CAS  PubMed  Google Scholar 

  76. Greenberg ES, Chong KK, Huynh KT, Tanaka R, Hoon DSB. Epigenetic biomarkers in skin cancer. Cancer Lett. 2014;342(2):170–7.

    Article  CAS  PubMed  Google Scholar 

  77. Marini A, Mirmohammadsadegh A, Nambiar S, Gustrau A, Ruzicka T, Hengge UR. Epigenetic inactivation of tumor suppressor genes in serum of patients with cutaneous melanoma. J Invest Dermatol. 2006;126(2):422–31.

    Article  CAS  PubMed  Google Scholar 

  78. Mori T, O’Day SJ, Umetani N, Martinez SR, Kitago M, Koyanagi K, Kuo C, Takeshima TL, Milford R, Wang HJ, Vu VD, Nguyen SL, Hoon DSB. Predictive utility of circulating methylated DNA in serum of melanoma patients receiving biochemotherapy. J Clin Oncol. 2005;23(36):9351–8.

    Article  CAS  PubMed  Google Scholar 

  79. Mori T, Martinez SR, O’Day SJ, et al. Estrogen receptor-alpha methylation predicts melanoma progression. Cancer Res. 2006;66(13):6692–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Hofman V, Ilie M, Long-Mira E, Giacchero D, Butori C, Dadone B, Selva E, Tanga V, Passeron T, Poissonnet G, Emile JF, Lacour JP, Bahadoran P, Hofman P. Usefulness of immunocytochemistry for the detection of the BRAF(V600E) mutation in circulating tumor cells from metastatic melanoma patients. J Invest Dermatol. 2013;133(5):1378–81.

    Article  CAS  PubMed  Google Scholar 

  81. Aya-Bonilla CA, Marsavela G, Freeman JB, Lomma C, Frank MH, Khattak MA, Meniawy TM, Millward M, Warkiani ME, Gray ES, Ziman M. Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device. Oncotarget. 2017;8(40):67355–68.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Gray ES, Reid AL, Bowyer S, Calapre L, Siew K, Pearce R, Cowell L, Frank MH, Millward M, Ziman M. Circulating melanoma cell subpopulations: their heterogeneity and differential responses to treatment. J Invest Dermatol. 2015;135(8):2040–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Khoja L, Shenjere P, Hodgson C, Hodgetts J, Clack G, Hughes A, Lorigan P, Dive C. Prevalence and heterogeneity of circulating tumour cells in metastatic cutaneous melanoma. Melanoma Res. 2014;24(1):40–6.

    Article  CAS  PubMed  Google Scholar 

  84. Khoja L, Lorigan P, Zhou C, Lancashire M, Booth J, Cummings J, Califano R, Clack G, Hughes A, Dive C. Biomarker utility of circulating tumor cells in metastatic cutaneous melanoma. J Invest Dermatol. 2013;133(6):1582–90.

    Article  CAS  PubMed  Google Scholar 

  85. Salvianti F, Costanza F, Sonnati G, et al. Detection and characterization of circulating tumor cells by quantitative real-time PCR. Methods Mol Biol. 2020;2065:139–51.

    Article  CAS  PubMed  Google Scholar 

  86. Xi L, Nicastri DG, El-Hefnawy T, et al. Optimal markers for real-time quantitative reverse transcription PCR detection of circulating tumor cells from melanoma, breast, colon, esophageal, head and neck, and lung cancers. Clin Chem. 2007;53(7):1206–15.

    Article  CAS  PubMed  Google Scholar 

  87. Reynolds SR, Albrecht J, Shapiro RL, Roses DF, Harris MN, Conrad A, Zeleniuch-Jacquotte A, Bystryn JC. Changes in the presence of multiple markers of circulating melanoma cells correlate with clinical outcome in patients with melanoma. Clin Cancer Res. 2003;9(4):1497–502.

    CAS  PubMed  Google Scholar 

  88. Samija I, Lukac J, Marić-Brozić J, et al. Prognostic value of microphthalmia-associated transcription factor and tyrosinase as markers for circulating tumor cells detection in patients with melanoma. Melanoma Res. 2010;20(4):293–302.

    Article  CAS  PubMed  Google Scholar 

  89. Onstenk W, Gratama JW, Foekens JA, Sleijfer S. Towards a personalized breast cancer treatment approach guided by circulating tumor cell (CTC) characteristics. Cancer Treat Rev. 2013;39(7):691–700.

    Article  CAS  PubMed  Google Scholar 

  90. Morimoto A, Mogami T, Watanabe M, Iijima K, Akiyama Y, Katayama K, Futami T, Yamamoto N, Sawada T, Koizumi F, Koh Y. High-density dielectrophoretic microwell array for detection, capture, and single-cell analysis of rare tumor cells in peripheral blood. PLoS One. 2015;10(6):e0130418.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Kiniwa Y, Nakamura K, Mikoshiba A, Akiyama Y, Morimoto A, Okuyama R. Diversity of circulating tumor cells in peripheral blood: detection of heterogeneous BRAF mutations in a patient with advanced melanoma by single-cell analysis. J Dermatol Sci. 2018;90(2):211–3.

    Article  CAS  PubMed  Google Scholar 

  92. Tsao H, Nadiminti U, Sober AJ, Bigby M. A meta-analysis of reverse transcriptase-polymerase chain reaction for tyrosinase mRNA as a marker for circulating tumor cells in cutaneous melanoma. Arch Dermatol. 2001;137(3):325–30.

    CAS  PubMed  Google Scholar 

  93. Hoon DS, Bostick P, Kuo C, Okamoto T, Wang HJ, Elashoff R, Morton DL. Molecular markers in blood as surrogate prognostic indicators of melanoma recurrence. Cancer Res. 2000;60(8):2253–7.

    CAS  PubMed  Google Scholar 

  94. Klinac D, Gray ES, Freeman JB, Reid A, Bowyer S, Millward M, Ziman M. Monitoring changes in circulating tumour cells as a prognostic indicator of overall survival and treatment response in patients with metastatic melanoma. BMC Cancer. 2014;14:423.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Aya-Bonilla CA, Morici M, Hong X, McEvoy AC, Sullivan RJ, Freeman J, Calapre L, Khattak MA, Meniawy T, Millward M, Ziman M, Gray ES. Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells. Br J Cancer. 2020;122(7):1059–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Lucci A, Hall CS, Patel SP, Narendran B, Bauldry JB, Royal RE, Karhade M, Upshaw JR, Wargo JA, Glitza IC, Wong MKK, Amaria RN, Tawbi HA, Diab A, Davies MA, Gershenwald JE, Lee JE, Hwu P, Ross MI. Circulating tumor cells and early relapse in node-positive melanoma. Clin Cancer Res. 2020;26(8):1886–95.

    Article  CAS  PubMed  Google Scholar 

  97. Hong X, Sullivan RJ, Kalinich M, Kwan TT, Giobbie-Hurder A, Pan S, LiCausi JA, Milner JD, Nieman LT, Wittner BS, Ho U, Chen T, Kapur R, Lawrence DP, Flaherty KT, Sequist LV, Ramaswamy S, Miyamoto DT, Lawrence M, et al. Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy. Proc Natl Acad Sci USA. 2018;115(10):2467–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Santiago-Walker A, Gagnon R, Mazumdar J, Casey M, Long GV, Schadendorf D, Flaherty K, Kefford R, Hauschild A, Hwu P, Haney P, O'Hagan A, Carver J, Goodman V, Legos J, Martin AM. Correlation of BRAF mutation status in circulating-free DNA and tumor and association with clinical outcome across four BRAFi and MEKi clinical trials. Clin Cancer Res. 2016;22(3):567–74.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Joe Barber Jr., PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Author information

Authors and Affiliations

  1. Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, Japan

    Hisashi Kanemaru MD, PhD, Yukari Mizukami MD, PhD, Akira Kaneko MD, Ikko Kajihara MD, PhD & Satoshi Fukushima MD, PhD

Authors
  1. Hisashi Kanemaru MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yukari Mizukami MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akira Kaneko MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ikko Kajihara MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Satoshi Fukushima MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hisashi Kanemaru MD, PhD.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Skin Cancer

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kanemaru, H., Mizukami, Y., Kaneko, A. et al. Promising Blood-Based Biomarkers for Melanoma: Recent Progress of Liquid Biopsy and Its Future Perspectives. Curr. Treat. Options in Oncol. 23, 562–577 (2022). https://doi.org/10.1007/s11864-022-00948-2

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-022-00948-2

Keywords

Search

Navigation