Skip to main content
Top

17-01-2018 | Melanoma | Article

Liquid biomarkers in melanoma: detection and discovery

Journal: Molecular Cancer

Authors: Su Yin Lim, Jenny H. Lee, Russell J. Diefenbach, Richard F. Kefford, Helen Rizos

Publisher: BioMed Central

Abstract

A vast array of tumor-derived genetic, proteomic and cellular components are constantly released into the circulation of cancer patients. These molecules including circulating tumor DNA and RNA, proteins, tumor and immune cells are emerging as convenient and accurate liquid biomarkers of cancer. Circulating cancer biomarkers provide invaluable information on cancer detection and diagnosis, prognosticate patient outcomes, and predict treatment response. In this era of effective molecular targeted treatments and immunotherapies, there is now an urgent need to implement use of these circulating biomarkers in the clinic to facilitate personalized therapy. In this review, we present recent findings in circulating melanoma biomarkers, examine the challenges and promise of evolving technologies used for liquid biomarker discovery, and discuss future directions and perspectives in melanoma biomarker research.
Literature
1.
Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, Hamid O, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367:1694–703.PubMedPubMedCentralCrossRef
2.
Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, Hodi FS, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16:908–18.PubMedCrossRef
3.
Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.PubMedPubMedCentralCrossRef
4.
Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, Patt D, et al. Pooled analysis of long-term survival data from phase II and phase III trials of Ipilimumab in Unresectable or metastatic melanoma. J Clin Oncol. 2015;33:1889–94.PubMedPubMedCentralCrossRef
5.
Long GV, Weber JS, Infante JR, Kim KB, Daud A, Gonzalez R, Sosman JA, et al. Overall survival and durable responses in patients with BRAF V600-mutant metastatic melanoma receiving Dabrafenib combined with Trametinib. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34:871–8.CrossRef
6.
Schachter J, Ribas A, Long GV, Arance A, Grob JJ, Mortier L, Daud A, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet. 2017;
7.
Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:1270–1.PubMedCrossRef
8.
Hodi FS, Chesney J, Pavlick AC, Robert C, Grossmann KF, McDermott DF, Linette GP, et al. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2016;17:1558–68.PubMedPubMedCentralCrossRef
9.
Hodi FS, Hwu WJ, Kefford R, Weber JS, Daud A, Hamid O, Patnaik A, et al. Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with Pembrolizumab. J Clin Oncol. 2016;34:1510–7.PubMedPubMedCentralCrossRef
10.
Pennock GK, Waterfield W, Wolchok JD. Patient responses to ipilimumab, a novel immunopotentiator for metastatic melanoma: how different are these from conventional treatment responses? Am J Clin Oncol. 2012;35:606–11.PubMedCrossRef
11.
Long GV, Hauschild A, Santinami M, Atkinson V, Mandala M, Chiarion-Sileni V, Larkin J, et al. Adjuvant Dabrafenib plus Trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;
12.
Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, et al. Prolonged survival in stage III melanoma with Ipilimumab adjuvant therapy. N Engl J Med. 2016;375:1845–55.PubMedPubMedCentralCrossRef
13.
Kulasingam V, Diamandis EP. Strategies for discovering novel cancer biomarkers through utilization of emerging technologies. Nat Clin Pract Oncol. 2008;5:588–99.PubMedCrossRef
14.
Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer. 2005;5:845–56.PubMedCrossRef
15.
Weinstein D, Leininger J, Hamby C, Safai B. Diagnostic and prognostic biomarkers in melanoma. J Clin Aesthet Dermatol. 2014;7:13–24.PubMedPubMedCentral
16.
Pantel K, Alix-Panabieres C. Real-time liquid biopsy in cancer patients: fact or fiction? Cancer Res. 2013;73:6384–8.PubMedCrossRef
17.
Balch CM, Gershenwald JE, Soong S-J, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27:6199–206.CrossRef
18.
Agarwala SS, Keilholz U, Gilles E, Bedikian AY, Wu J, Kay R, Stein CA, et al. LDH correlation with survival in advanced melanoma from two large, randomised trials (Oblimersen GM301 and EORTC 18951). European journal of cancer (Oxford, England: 1990). 2009;45:1807–14.CrossRef
19.
Long GV, Grob JJ, Nathan P, Ribas A, Robert C, Schadendorf D, Lane SR, et al. Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomised trials. Lancet Oncol. 2016;17:1743–54.PubMedCrossRef
20.
Diem S, Kasenda B, Martin-Liberal J, Lee A, Chauhan D, Gore M, Larkin J. Prognostic score for patients with advanced melanoma treated with ipilimumab. Eur J Cancer. 2015;51:2785–91.PubMedCrossRef
21.
Vereecken P, Cornelis F, Van Baren N, Vandersleyen V, Baurain JFA. Synopsis of serum biomarkers in cutaneous melanoma patients. Dermatol Res Pract. 2012;2012:260643.PubMedPubMedCentral
22.
Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366:883–92.PubMedPubMedCentralCrossRef
23.
Couraud S, Vaca-Paniagua F, Villar S, Oliver J, Schuster T, Blanche H, Girard N, et al. Noninvasive diagnosis of actionable mutations by deep sequencing of circulating free DNA in lung cancer from never-smokers: a proof-of-concept study from BioCAST/IFCT-1002. Clin Cancer Res. 2014;20:4613–24.PubMedCrossRef
24.
Andersson AK, Ma J, Wang J, Chen X, Gedman AL, Dang J, Nakitandwe J, et al. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. Nat Genet. 2015;47:330–7.PubMedPubMedCentralCrossRef
25.
Anderson NL, Anderson NG. The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics. 2002;1:845–67.PubMedCrossRef
26.
Khan A. Detection and quantitation of forty eight cytokines, chemokines, growth factors and nine acute phase proteins in healthy human plasma, saliva and urine. J Proteome. 2012;75:4802–19.CrossRef
27.
Hsieh SY, Chen RK, Pan YH, Lee HL. Systematical evaluation of the effects of sample collection procedures on low-molecular-weight serum/plasma proteome profiling. Proteomics. 2006;6:3189–98.PubMedCrossRef
28.
Banks RE, Stanley AJ, Cairns DA, Barrett JH, Clarke P, Thompson D, Selby PJ. Influences of blood sample processing on low-molecular-weight proteome identified by surface-enhanced laser desorption/ionization mass spectrometry. Clin Chem. 2005;51:1637–49.PubMedCrossRef
29.
Lum G, Gambino SRA. Comparison of serum versus heparinized plasma for routine chemistry tests. Am J Clin Pathol. 1974;61:108–13.PubMedCrossRef
30.
Ladenson JH, Tsai LM, Michael JM, Kessler G, Joist JH. Serum versus heparinized plasma for eighteen common chemistry tests: is serum the appropriate specimen? Am J Clin Pathol. 1974;62:545–52.PubMedCrossRef
31.
Yu Z, Kastenmuller G, He Y, Belcredi P, Moller G, Prehn C, Mendes J, et al. Differences between human plasma and serum metabolite profiles. PLoS One. 2011;6:e21230.PubMedPubMedCentralCrossRef
32.
Luque-Garcia JL, Neubert TA. Sample preparation for serum/plasma profiling and biomarker identification by mass spectrometry. J Chromatogr A. 2007;1153:259–76.PubMedCrossRef
33.
Parker CE, Borchers CH. Mass spectrometry based biomarker discovery, verification, and validation--quality assurance and control of protein biomarker assays. Mol Oncol. 2014;8:840–58.PubMedPubMedCentralCrossRef
34.
Chen YT, Chen HW, Domanski D, Smith DS, Liang KH, CC W, Chen CL, et al. Multiplexed quantification of 63 proteins in human urine by multiple reaction monitoring-based mass spectrometry for discovery of potential bladder cancer biomarkers. J Proteome. 2012;75:3529–45.CrossRef
35.
Anjo SI, Santa C, Manadas B. SWATH-MS as a tool for biomarker discovery: from basic research to clinical applications. Proteomics. 2017;17
36.
Marx V. Targeted proteomics. Nat Methods. 2013;10:19–22.PubMedCrossRef
37.
Karsan A, Eigl BJ, Flibotte S, Gelmon K, Switzer P, Hassell P, Harrison D, et al. Analytical and preanalytical biases in serum proteomic pattern analysis for breast cancer diagnosis. Clin Chem. 2005;51:1525–8.PubMedCrossRef
38.
Matharoo-Ball B, Ratcliffe L, Lancashire L, Ugurel S, Miles AK, Weston DJ, Rees R, et al. Diagnostic biomarkers differentiating metastatic melanoma patients from healthy controls identified by an integrated MALDI-TOF mass spectrometry/bioinformatic approach. Proteomics Clin Appl. 2007;1:605–20.PubMedCrossRef
39.
Mian S, Ugurel S, Parkinson E, Schlenzka I, Dryden I, Lancashire L, Ball G, et al. Serum proteomic fingerprinting discriminates between clinical stages and predicts disease progression in melanoma patients. J Clin Oncol. 2005;23:5088–93.PubMedCrossRef
40.
Mactier S, Kaufman KL, Wang P, Crossett B, Pupo GM, Kohnke PL, Thompson JF, et al. Protein signatures correspond to survival outcomes of AJCC stage III melanoma patients. Pigment Cell Melanoma Res. 2014;27:1106–16.PubMedPubMedCentralCrossRef
41.
Tighe PJ, Ryder RR, Todd I, Fairclough LCELISA. In the multiplex era: potentials and pitfalls. Proteomics Clin Appl. 2015;9:406–22.PubMedCrossRef
42.
Fu Q, Schoenhoff FS, Savage WJ, Zhang P, Van Eyk JE. Multiplex assays for biomarker research and clinical application: translational science coming of age. Proteomics Clin Appl. 2010;4:271–84.PubMedCrossRef
43.
Kraemer S, Vaught JD, Bock C, Gold L, Katilius E, Keeney TR, Kim N, et al. From SOMAmer-based biomarker discovery to diagnostic and clinical applications: a SOMAmer-based, streamlined multiplex proteomic assay. PLoS One. 2011;6:e26332.PubMedPubMedCentralCrossRef
44.
Powell K. New platform for cataloging hundreds of proteins gets test drive. Nat Med. 2014;20:1082–3.PubMedCrossRef
45.
Lim SY, Lee JH, Welsh SJ, Ahn SB, Breen E, Khan A, Carlino MS, et al. Evaluation of two high-throughput proteomic technologies for plasma biomarker discovery in immunotherapy-treated melanoma patients. Biomark Res. 2017;5:32.PubMedPubMedCentralCrossRef
46.
Yuan J, Zhou J, Dong Z, Tandon S, Kuk D, Panageas KS, Wong P, et al. Pretreatment serum VEGF is associated with clinical response and overall survival in advanced melanoma patients treated with ipilimumab. Cancer Immunol Res. 2014;2:127–32.PubMedCrossRef
47.
Wilmott JS, Haydu LE, Menzies AM, Lum T, Hyman J, Thompson JF, Hersey P, et al. Dynamics of chemokine, cytokine, and growth factor serum levels in BRAF-mutant melanoma patients during BRAF inhibitor treatment. J Immunol. 2014;192:2505–13.PubMedCrossRef
48.
Nikolaev S, Lemmens L, Koessler T, Blouin JL, Nouspikel T. Circulating tumoral DNA: Preanalytical validation and quality control in a diagnostic laboratory. Anal Biochem. 2017;542:34–9.PubMedCrossRef
49.
van Dessel LF, Beije N, Helmijr JC, Vitale SR, Kraan J, Look MP, de Wit R, et al. Application of circulating tumor DNA in prospective clinical oncology trials - standardization of preanalytical conditions. Mol Oncol. 2017;11:295–304.PubMedPubMedCentralCrossRef
50.
Perez-Barrios C, Nieto-Alcolado I, Torrente M, Jimenez-Sanchez C, Calvo V, Gutierrez-Sanz L, Palka M, et al. Comparison of methods for circulating cell-free DNA isolation using blood from cancer patients: impact on biomarker testing. Transl Lung Cancer Res. 2016;5:665–72.PubMedPubMedCentralCrossRef
51.
Kloten V, Ruchel N, Bruchle NO, Gasthaus J, Freudenmacher N, Steib F, Mijnes J, et al. Liquid biopsy in colon cancer: comparison of different circulating DNA extraction systems following absolute quantification of KRAS mutations using Intplex allele-specific PCR. Oncotarget. 2017;8:86253–63.PubMedPubMedCentralCrossRef
52.
Cheng F, Su L, Qian C. Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer. Oncotarget. 2016;7:48832–41.PubMedPubMedCentral
53.
Han X, Wang J, Sun Y. Circulating tumor DNA as biomarkers for cancer detection. Genomics Proteomics Bioinformatics. 2017;15:59–72.PubMedPubMedCentralCrossRef
54.
Lo YM, Zhang J, Leung TN, Lau TK, Chang AM, Hjelm NM. Rapid clearance of fetal DNA from maternal plasma. Am J Hum Genet. 1999;64:218–24.PubMedPubMedCentralCrossRef
55.
SC Y, Lee SW, Jiang P, Leung TY, Chan KC, Chiu RW, Lo YM. High-resolution profiling of fetal DNA clearance from maternal plasma by massively parallel sequencing. Clin Chem. 2013;59:1228–37.CrossRef
56.
Underhill HR, Kitzman JO, Hellwig S, Welker NC, Daza R, Baker DN, Gligorich KM, et al. Fragment length of circulating tumor DNA. PLoS Genet. 2016;12:e1006162.PubMedPubMedCentralCrossRef
57.
Chabon JJ, Simmons AD, Lovejoy AF, Esfahani MS, Newman AM, Haringsma HJ, Kurtz DM, et al. Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients. Nat Commun. 2016;7:11815.PubMedPubMedCentralCrossRef
58.
John T, Bowden JJ, Clarke S, Fox SB, Garrett K, Horwood K, Karapetis CS. Australian recommendations for EGFR T790M testing in advanced non-small cell lung cancer. Asia Pac J Clin Oncol. 2017;13:296–303.PubMedCrossRef
59.
Quereux G, Herbreteau G, Knol AC, Vallee A, Khammari A, Theoleyre S, Saint-Jean M, et al. Efficient treatment of a metastatic melanoma patient with a combination of BRAF and MEK inhibitors based on circulating tumor DNA analysis: a case report. BMC Res Notes. 2017;10:320.PubMedPubMedCentralCrossRef
60.
Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, Knippers R. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 2001;61:1659–65.PubMed
61.
Heitzer E, Ulz P, Geigl JB. Circulating tumor DNA as a liquid biopsy for cancer. Clin Chem. 2015;61:112–23.PubMedCrossRef
62.
Daniotti M, Vallacchi V, Rivoltini L, Patuzzo R, Santinami M, Arienti F, Cutolo G, et al. Detection of mutated BRAFV600E variant in circulating DNA of stage III-IV melanoma patients. Int J Cancer. 2007;120:2439–44.PubMedCrossRef
63.
Lee JH, Long GV, Boyd S, Lo S, Menzies AM, Tembe V, Guminski A, et al. Circulating tumour DNA predicts response to anti-PD1 antibodies in metastatic melanoma. Ann Oncol. 2017;
64.
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.PubMedCrossRef
65.
Gray ES, Rizos H, Reid AL, Boyd SC, Pereira MR, Lo J, Tembe V, et al. Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma. Oncotarget. 2015;6:42008–18.PubMedPubMedCentral
66.
Bidard FC, Madic J, Mariani P, Piperno-Neumann S, Rampanou A, Servois V, Cassoux N, et al. Detection rate and prognostic value of circulating tumor cells and circulating tumor DNA in metastatic uveal melanoma. Int J Cancer. 2014;134:1207–13.PubMedCrossRef
67.
Warton K, Mahon KL, Samimi G. Methylated circulating tumor DNA in blood: power in cancer prognosis and response. Endocr Relat Cancer. 2016;23:R157–71.PubMedPubMedCentralCrossRef
68.
Micevic G, Theodosakis N, Bosenberg M, Aberrant DNA. Methylation in melanoma: biomarker and therapeutic opportunities. Clin Epigenetics. 2017;9:34.PubMedPubMedCentralCrossRef
69.
Wouters J, Vizoso M, Martinez-Cardus A, Carmona FJ, Govaere O, Laguna T, Joseph J, et al. Comprehensive DNA methylation study identifies novel progression-related and prognostic markers for cutaneous melanoma. BMC Med. 2017;15:101.PubMedPubMedCentralCrossRef
70.
Soozangar N, Sadeghi MR, Jeddi F, Somi MH, Shirmohamadi M, Samadi N. Comparison of genome-wide analysis techniques to DNA methylation analysis in human cancer. J Cell Physiol. 2017;
71.
Mori T, O'Day SJ, Umetani N, Martinez SR, Kitago M, Koyanagi K, Kuo C, et al. Predictive utility of circulating methylated DNA in serum of melanoma patients receiving biochemotherapy. J Clin Oncol. 2005;23:9351–8.PubMedPubMedCentralCrossRef
72.
Mori T, Martinez SR, O'Day SJ, Morton DL, Umetani N, Kitago M, Tanemura A, et al. Estrogen receptor-alpha methylation predicts melanoma progression. Cancer Res. 2006;66:6692–8.PubMedPubMedCentralCrossRef
73.
Di Meo A, Bartlett J, Cheng Y, Pasic MD, Yousef GM. Liquid biopsy: a step forward towards precision medicine in urologic malignancies. Mol Cancer. 2017;16:80.PubMedPubMedCentralCrossRef
74.
Wan J, Zhu L, Jiang Z, Cheng K. Monitoring of plasma cell-free DNA in predicting postoperative recurrence of clear cell renal cell carcinoma. Urol Int. 2013;91:273–8.PubMedCrossRef
75.
Thierry AR, Mouliere F, Gongora C, Ollier J, Robert B, Ychou M, Del Rio M, et al. Origin and quantification of circulating DNA in mice with human colorectal cancer xenografts. Nucleic Acids Res. 2010;38:6159–75.PubMedPubMedCentralCrossRef
76.
Sorber L, Zwaenepoel K, Deschoolmeester V, Roeyen G, Lardon F, Rolfo C, Pauwels PA. Comparison of cell-free DNA isolation kits: isolation and quantification of cell-free DNA in plasma. J Mol Diagn. 2017;19:162–8.PubMedCrossRef
77.
Lee JHJ, Long GV, Menzies AM, Gunninski AD, Kefford R, Rizos H, Carlino MS. Analysis of circulating tumor DNA (ctDNA) in pseudoprogression in anti-PD1 treated metastatic melanoma (MM). J Clin Oncol. 2017;35
78.
Shi T, Gao G, Cao Y. Long Noncoding RNAs as novel biomarkers have a promising future in cancer diagnostics. Dis Markers. 2016;2016:9085195.PubMedPubMedCentralCrossRef
79.
Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol. 2011;13:423–33.PubMedPubMedCentralCrossRef
80.
Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, Mitchell PS, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A. 2011;108:5003–8.PubMedPubMedCentralCrossRef
81.
Chen X, Liang H, Zhang J, Zen K, Zhang CY. Secreted microRNAs: a new form of intercellular communication. Trends Cell Biol. 2012;22:125–32.PubMedCrossRef
82.
Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.PubMedPubMedCentralCrossRef
83.
Deng H, Wang JM, Li M, Tang R, Tang K, Su Y, Hou Y, et al. Long non-coding RNAs: new biomarkers for prognosis and diagnosis of colon cancer. Tumour Biol. 2017;39:1010428317706332.PubMed
84.
Tian T, Wang J, Zhou XA. Review: microRNA detection methods. Org Biomol Chem. 2015;13:2226–38.PubMedCrossRef
85.
Aftab MN, Dinger ME, Perera RJ. The role of microRNAs and long non-coding RNAs in the pathology, diagnosis, and management of melanoma. Arch Biochem Biophys. 2014;563:60–70.PubMedCrossRef
86.
Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2014;15:7–21.PubMedCrossRef
87.
Fattore L, Costantini S, Malpicci D, Ruggiero CF, Ascierto PA, Croce CM, Mancini R, et al. MicroRNAs in melanoma development and resistance to target therapy. Oncotarget. 2017;8:22262–78.PubMedPubMedCentralCrossRef
88.
Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids--the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011;8:467–77.PubMedPubMedCentralCrossRef
89.
Kanemaru H, Fukushima S, Yamashita J, Honda N, Oyama R, Kakimoto A, Masuguchi S, et al. The circulating microRNA-221 level in patients with malignant melanoma as a new tumor marker. J Dermatol Sci. 2011;61:187–93.PubMedCrossRef
90.
Friedman EB, Shang S, de Miera EV, Fog JU, Teilum MW, Ma MW, Berman RS, et al. Serum microRNAs as biomarkers for recurrence in melanoma. J Transl Med. 2012;10:155.PubMedPubMedCentralCrossRef
91.
Wang F, Ren S, Chen R, Lu J, Shi X, Zhu Y, Zhang W, et al. Development and prospective multicenter evaluation of the long noncoding RNA MALAT-1 as a diagnostic urinary biomarker for prostate cancer. Oncotarget. 2014;5:11091–102.PubMedPubMedCentral
92.
Felicetti F, De Feo A, Coscia C, Puglisi R, Pedini F, Pasquini L, Bellenghi M, et al. Exosome-mediated transfer of miR-222 is sufficient to increase tumor malignancy in melanoma. J Transl Med. 2016;14:56.PubMedPubMedCentralCrossRef
93.
Isola AL, Eddy K, Chen S. Biology, therapy and implications of tumor exosomes in the progression of melanoma. Cancers (Basel). 2016;8
94.
Li P, Kaslan M, Lee SH, Yao J, Gao Z. Progress in exosome isolation techniques. Theranostics. 2017;7:789–804.PubMedPubMedCentralCrossRef
95.
Giebel B, Helmbrecht C. Methods to analyze EVs. Methods Mol Biol. 2017;1545:1–20.PubMedCrossRef
96.
Yoshioka Y, Kosaka N, Konishi Y, Ohta H, Okamoto H, Sonoda H, Nonaka R, et al. Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen. Nat Commun. 2014;5:3591.PubMedPubMedCentralCrossRef
97.
Pfeffer SR, Grossmann KF, Cassidy PB, Yang CH, Fan M, Kopelovich L, Leachman SA, et al. Detection of Exosomal miRNAs in the plasma of melanoma patients. J Clin Med. 2015;4:2012–27.PubMedPubMedCentralCrossRef
98.
Lunavat TR, Cheng L, Einarsdottir BO, Olofsson Bagge R, Veppil Muralidharan S, Sharples RA, Lasser C, et al. BRAFV600 inhibition alters the microRNA cargo in the vesicular secretome of malignant melanoma cells. Proc Natl Acad Sci U S A. 2017;114:E5930–9.PubMedCrossRef
99.
Yuan J, Hegde PS, Clynes R, Foukas PG, Harari A, Kleen TO, Kvistborg P, et al. Novel technologies and emerging biomarkers for personalized cancer immunotherapy. J Immunother Cancer. 2016;4:3.PubMedPubMedCentralCrossRef
100.
Diaz LA Jr, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 2014;32:579–86.PubMedPubMedCentralCrossRef
101.
Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, Beitsch PD, et al. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res. 2004;10:8152–62.PubMedCrossRef
102.
Pantel K, Speicher MR. The biology of circulating tumor cells. Oncogene. 2016;35:1216–24.PubMedCrossRef
103.
Perez-Callejo D, Romero A, Provencio M, Torrente M. Liquid biopsy based biomarkers in non-small cell lung cancer for diagnosis and treatment monitoring. Transl Lung Cancer Res. 2016;5:455–65.PubMedPubMedCentralCrossRef
104.
Krebs MG, Sloane R, Priest L, Lancashire L, Hou JM, Greystoke A, Ward TH, et al. Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. J Clin Oncol. 2011;29:1556–63.PubMedCrossRef
105.
Punnoose EA, Atwal S, Liu W, Raja R, Fine BM, Hughes BG, Hicks RJ, et al. Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clin Cancer Res. 2012;18:2391–401.PubMedCrossRef
106.
Alix-Panabieres C, Pantel K. Circulating tumor cells: liquid biopsy of cancer. Clin Chem. 2013;59:110–8.PubMedCrossRef
107.
Vona G, Sabile A, Louha M, Sitruk V, Romana S, Schutze K, Capron F, et al. Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulatingtumor cells. Am J Pathol. 2000;156:57–63.PubMedPubMedCentralCrossRef
108.
Wu Y, Deighan CJ, Miller BL, Balasubramanian P, Lustberg MB, Zborowski M, Chalmers JJ. Isolation and analysis of rare cells in the blood of cancer patients using a negative depletion methodology. Methods. 2013;64:169–82.PubMedCrossRef
109.
Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007;450:1235–9.PubMedPubMedCentralCrossRef
110.
Warkiani ME, Guan G, Luan KB, Lee WC, Bhagat AA, Chaudhuri PK, Tan DS, et al. Slanted spiral microfluidics for the ultra-fast, label-free isolation of circulating tumor cells. Lab Chip. 2014;14:128–37.PubMedCrossRef
111.
Warkiani ME, Khoo BL, Wu L, Tay AK, Bhagat AA, Han J, Lim CT. Ultra-fast, label-free isolation of circulating tumor cells from blood using spiral microfluidics. Nat Protoc. 2016;11:134–48.PubMedCrossRef
112.
Hida T, Yoneta A, Wakamatsu K, Yanagisawa K, Ishii-Osai Y, Kan Y, Kato J, et al. Circulating melanoma cells as a potential biomarker to detect metastasis and evaluate prognosis. Australas J Dermatol. 2016;57:145–9.PubMedCrossRef
113.
Palmieri G, Ascierto PA, Perrone F, Satriano SM, Ottaiano A, Daponte A, Napolitano M, et al. Prognostic value of circulating melanoma cells detected by reverse transcriptase-polymerase chain reaction. J Clin Oncol. 2003;21:767–73.PubMedCrossRef
114.
Koyanagi K, Kuo C, Nakagawa T, Mori T, Ueno H, Lorico AR Jr, Wang HJ, et al. Multimarker quantitative real-time PCR detection of circulating melanoma cells in peripheral blood: relation to disease stage in melanoma patients. Clin Chem. 2005;51:981–8.PubMedPubMedCentralCrossRef
115.
Karakousis G, Yang R, Xu X. Circulating melanoma cells as a predictive biomarker. J Invest Dermatol. 2013;133:1460–2.PubMedCrossRef
116.
Mumford BS, Robertson GP. Circulating melanoma cells in the diagnosis and monitoring of melanoma: an appraisal of clinical potential. Mol Diagn Ther. 2014;18:175–83.PubMedPubMedCentralCrossRef
117.
Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–7.PubMedPubMedCentralCrossRef
118.
Meng X, Huang Z, Teng F, Xing L, Predictive YJ. Biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy. Cancer Treat Rev. 2015;41:868–76.PubMedCrossRef
119.
Teng MW, Ngiow SF, Ribas A, Smyth MJ. Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res. 2015;75:2139–45.PubMedPubMedCentralCrossRef
120.
Perfetto SP, Chattopadhyay PK, Roederer M. Seventeen-colour flow cytometry: unravelling the immune system. Nat Rev Immunol. 2004;4:648–55.PubMedCrossRef
121.
Chattopadhyay PK, Perfetto SP, Roederer M. The colorful future of cell analysis by flow cytometry. Discov Med. 2004;4:255–62.PubMed
122.
Ornatsky O, Bandura D, Baranov V, Nitz M, Winnik MA, Tanner S. Highly multiparametric analysis by mass cytometry. J Immunol Methods. 2010;361:1–20.PubMedCrossRef
123.
Bendall SC, Nolan GP, Roederer M, Chattopadhyay PK. A deep profiler's guide to cytometry. Trends Immunol. 2012;33:323–32.PubMedPubMedCentralCrossRef
124.
Maecker HT, McCoy JP, Nussenblatt R. Standardizing immunophenotyping for the human immunology project. Nat Rev Immunol. 2012;12:191–200.PubMedPubMedCentral
125.
van Dongen JJ, Lhermitte L, Bottcher S, Almeida J, van der Velden VH, Flores-Montero J, Rawstron A, et al. EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia. 2012;26:1908–75.PubMedPubMedCentralCrossRef
126.
Newell EW. Higher throughput methods of identifying T cell epitopes for studying outcomes of altered antigen processing and presentation. Front Immunol. 2013;4:430.PubMedPubMedCentralCrossRef
127.
Andersen RS, Kvistborg P, Frosig TM, Pedersen NW, Lyngaa R, Bakker AH, Shu CJ, et al. Parallel detection of antigen-specific T cell responses by combinatorial encoding of MHC multimers. Nat Protoc. 2012;7:891–902.PubMedCrossRef
128.
Martens A, Wistuba-Hamprecht K, Geukes Foppen M, Yuan J, Postow MA, Wong P, Romano E, et al. Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with Ipilimumab. Clin Cancer Res. 2016;22:2908–18.PubMedCrossRefPubMedCentral
129.
Weide B, Martens A, Hassel JC, Berking C, Postow MA, Bisschop K, Simeone E, et al. Baseline biomarkers for outcome of melanoma patients treated with Pembrolizumab. Clin Cancer Res. 2016;22:5487–96.PubMedPubMedCentralCrossRef
130.
Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, Xu W, et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature. 2017;545:60–5.PubMedPubMedCentralCrossRef
131.
Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O'Dwyer PJ, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010;363:809–19.PubMedPubMedCentralCrossRef
132.
Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364:2507–16.PubMedPubMedCentralCrossRef
133.
McArthur GA, Chapman PB, Robert C, Larkin J, Haanen JB, Dummer R, Ribas A, et al. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol. 2014;15:323–32.PubMedPubMedCentralCrossRef
134.
Ascierto PA, Minor D, Ribas A, Lebbe C, O'Hagan A, Arya N, Guckert M, et al. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol. 2013;31:3205–11.PubMedCrossRef
135.
Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380:358–65.PubMedCrossRef
136.
Hauschild A, Grobb J, Demidov L, Jouary T, Gutzmer R, Millward M, Rutkowski P, et al. 1092PDAN update on overall survival (OS) and follow-on therapies in break-3, a phase iii, randomized trial: dabrafenib (D) vs. dacarbazine (DTIC) in patients (PTS) with braf v600e mutation-positive metastatic melanoma (MM). Annals of oncology: official journal of the European Society for Medical Oncology 2014;25:iv378.
137.
Schreuer M, Meersseman G, Van Den Herrewegen S, Jansen Y, Chevolet I, Bott A, Wilgenhof 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.PubMedPubMedCentralCrossRef
138.
Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, Demidov LV, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367:107–14.PubMedCrossRef
139.
Schadendorf D, Long GV, Stroiakovski D, Karaszewska B, Hauschild A, Levchenko E, Chiarion-Sileni V, et al. Three-year pooled analysis of factors associated with clinical outcomes across dabrafenib and trametinib combination therapy phase 3 randomised trials. European journal of cancer (Oxford, England: 1990). 2017;82:45–55.CrossRef
140.
Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, Lichinitser M, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30–9.PubMedCrossRef
141.
Ascierto PA, McArthur GA, Dreno B, Atkinson V, Liszkay G, Di Giacomo AM, Mandala M, et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016;17:1248–60.PubMedCrossRef
142.
Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369:122–33.PubMedPubMedCentralCrossRef
143.
Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372:2521–32.PubMedCrossRef
144.
Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–30.PubMedCrossRef
145.
Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, Lao CD, et al. Overall survival with combined Nivolumab and Ipilimumab in advanced melanoma. N Engl J Med. 2017;
146.
Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, et al. Talimogene Laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33:2780–8.PubMedCrossRef
147.
Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, Fleming ID, et al. Final version of the American joint committee on cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19:3635–48.PubMedCrossRef
148.
Duncan LM, Deeds J, Cronin FE, Donovan M, Sober AJ, Kauffman M, McCarthy JJ. Melastatin expression and prognosis in cutaneous malignant melanoma. J Clin Oncol. 2001;19:568–76.PubMedCrossRef
149.
Francken AB, Shaw HM, Thompson JF, Soong SJ, Accortt NA, Azzola MF, Scolyer RA, et al. The prognostic importance of tumor mitotic rate confirmed in 1317 patients with primary cutaneous melanoma and long follow-up. Ann Surg Oncol. 2004;11:426–33.PubMedCrossRef
150.
Thomas NE, Edmiston SN, Alexander A, Groben PA, Parrish E, Kricker A, Armstrong BK, et al. Association between NRAS and BRAF mutational status and melanoma-specific survival among patients with higher-risk primary melanoma. JAMA Oncol. 2015;1:359–68.PubMedPubMedCentralCrossRef
151.
Khosrotehrani K, van der Ploeg AP, Siskind V, Hughes MC, Wright A, Thomas J, Barbour A, et al. Nomograms to predict recurrence and survival in stage IIIB and IIIC melanoma after therapeutic lymphadenectomy. Eur J Cancer. 2014;50:1301–9.PubMedCrossRef
152.
Manola J, Atkins M, Ibrahim J, Kirkwood J. Prognostic factors in metastatic melanoma: a pooled analysis of eastern cooperative oncology group trials. J Clin Oncol. 2000;18:3782–93.PubMedCrossRef
153.
Eton O, Legha SS, Moon TE, Buzaid AC, Papadopoulos NE, Plager C, Burgess AM, et al. Prognostic factors for survival of patients treated systemically for disseminated melanoma. J Clin Oncol. 1998;16:1103–11.PubMedCrossRef
154.
Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, Kefford R, Joshua AM, et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA. 2016;315:1600–9.PubMedCrossRef