A Systematic Review and Meta-Analysis of Gene Expression Profiling for Primary Cutaneous Melanoma Prognosis
Main Article Content
Keywords
gene expression profile, melanoma prognosis, systematic review and meta analysis
Abstract
To decrease morbidity and mortality from melanoma, it is imperative to identify patients who are at high risk for developing widespread disease. Gene expression profiling (GEP) technology may impact melanoma management as physicians are better equipped to measure prognosis. Many different GEP signatures have been investigated. We searched Pubmed, Cochrane CENTRAL, and Embase for studies on GEP in primary melanoma prognosis and assessed GEP signatures for prognostic and analytic validity and clinical impact. The relationship between GEP and survival was measured using hazard ratios (HR) and odds ratios (OR). We found twenty-nine articles comprising 9 gene signatures meeting inclusion criteria and conducted a meta-analysis on 6 studies on a 31-gene signature. High-risk GEP status was associated with poorer recurrence-free survival (HR=7.22; 95% CI, 4.75-10.98), distant metastasis-free survival (HR=6.62; 95% CI, 4.91-8.91), and overall survival (HR=7.06; 95% CI, 4.44-11.22); as well as sentinel lymph node biopsy positivity (OR=2.99; 95% CI, 2.15-4.15). With recent improvements in treating advanced melanoma, accurately assessing prognosis is important. This study has clinical implications for melanoma patients who may benefit from prognostic testing. These results may be useful to clinicians when ordering GEP testing and help them make better management decisions.
References
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14. Cook RW, Middlebrook B, Wilkinson J, et al. Analytic validity of DecisionDx-Melanoma, a gene expression profile test for determining metastatic risk in melanoma patients. Diagn Pathol. 2018;13(1):13.
15. Berger AC, Davidson RS, Poitras JK, et al. Clinical impact of a 31-gene expression profile test for cutaneous melanoma in 156 prospectively and consecutively tested patients. Curr Med Res Opin. 2016;32(9):1599-604.
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19. Farberg AS, Glazer AM, White R, Rigel DS. Impact of a 31-gene Expression Profiling Test for Cutaneous Melanoma on Dermatologists' Clinical Management Decisions. J Drugs Dermatol. 2017;16(5):428-431.
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21. Gerami P, Cook RW, Wilkinson J, et al. Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res. 2015;21(1):175-83.
22. Gerami P, Cook RW, Russell MC, et al. Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. J Am Acad Dermatol. 2015;72(5):780-5.e3.
23. Cook RW, Covington KR, Monzon FA. Continued evaluation of a 31-gene expression profile to predict metastasis in an expanded cohort of 782 cutaneous melanoma patients. Pigment Cell Melanoma Res. 2017;30:e73.
24. Ferris LK, Farberg AS, Middlebrook B, et al. Identification of high-risk cutaneous melanoma tumors is improved when combining the online American Joint Committee on Cancer Individualized Melanoma Patient Outcome Prediction Tool with a 31-gene expression profile-based classification. J Am Acad Dermatol. 2017;76(5):818-825.e3.
25. Zager JS, Gastman BR, Leachman S, et al. Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. BMC Cancer. 2018;18(1):130.
26. Greenhaw BN, Zitelli JA, Brodland DG. Estimation of Prognosis in Invasive Cutaneous Melanoma: An Independent Study of the Accuracy of a Gene Expression Profile Test. Dermatol Surg. 2018;
27. Hsueh EC, Debloom JR, Lee J, et al. Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test. J Hematol Oncol. 2017;10(1):152.
28. Keller JK, Schwartz T, Lizalek JM, Hsueh EC. Utility of Gene Expression Profiling in Determining Necessity of Sentinel Node Biopsy in Melanoma. Ann Surg Oncol. 2017;24(S1):S148.
29. Huang X, Hewgley WP, Guerrero W, Fleming M. Application of Gene Expression Profiling in the Management of
Cutaneous Melanoma. Ann Surg Oncol. 2017;24(S1):S144.
30. Cook RW, Covington KR, Monzon FA. Prognostic value of non-sentinel lymph node (non-SLN) status and a prognostic 31-gene expression profile (GEP) in stage III cutaneous melanoma patients Pigment Cell Melanoma Res. 2018;31:e144.
31. Keller J, Schwartz T, Lizalek J, Hsueh E. Exploring the Role of Gene Expression Profiling in the Prediction of Non-Sentinel Node Status in Cutaneous Melanoma. Ann Surg Oncol. 2018;24(S1):S67.
32. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Cutaneous Melanoma. 2019.
33. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16. doi:10.1186/1745-6215-8-16.
34. Hayden JA, Van der windt DA, Cartwright JL, Côté P, Bombardier C. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013;158(4):280-6.
2. Alonso SR, Tracey L, Ortiz P, et al. A high-throughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis. Cancer Res. 2007;67(7):3450-60.
3. Winnepenninckx V, Lazar V, Michiels S, et al. Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst. 2006;98(7):472-82.
4. Conway C, Mitra A, Jewell R, et al. Gene expression profiling of paraffin-embedded primary melanoma using the DASL assay identifies increased osteopontin expression as predictive of reduced relapse-free survival. Clin Cancer Res. 2009;15(22):6939-46.
5. Jewell R, Conway C, Mitra A, et al. Patterns of expression of DNA repair genes and relapse from melanoma. Clin Cancer Res. 2010;16(21):5211-21.
6. Harbst K, Staaf J, Lauss M, et al. Molecular profiling reveals low- and high-grade forms of primary melanoma. Clin Cancer Res. 2012;18(15):4026-36.
7. Jonsson G, Busch C, Knappskog S, Geisler J, Miletic H, Ringner M, et al. Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome. Clin Cancer Res 2010;16:3356–67.
8. Nsengimana J, Laye J, Filia A, et al. Independent replication of a melanoma subtype gene signature and evaluation of its prognostic value and biological correlates in a population cohort. Oncotarget. 2015;6(13):11683-93.
9. Badal B, Solovyov A, Di cecilia S, et al. Transcriptional dissection of melanoma identifies a high-risk subtype underlying TP53 family genes and epigenome deregulation. JCI Insight. 2017;2(9)
10. Meyer S, Fuchs TJ, Bosserhoff AK, et al. A seven-marker signature and clinical outcome in malignant melanoma: a large-scale tissue-microarray study with two independent patient cohorts. PLoS ONE. 2012;7(6):e38222.
11. Brunner G, Reitz M, Heinecke A, et al. A nine-gene signature predicting clinical outcome in cutaneous melanoma. J Cancer Res Clin Oncol. 2013;139(2):249-58.
12. Brunner G, Gambichler T, Reinhold U, et al. A prognostic gene expression profile complements staging of thin fatal melanomas and melanomas with known sentinel lymph node status. Oncol Res Treat. 2018;41(S1):162.
13. Sivendran S, Chang R, Pham L, et al. Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II-III resectable disease. J Invest Dermatol. 2014;134(8):2202-2211.
14. Cook RW, Middlebrook B, Wilkinson J, et al. Analytic validity of DecisionDx-Melanoma, a gene expression profile test for determining metastatic risk in melanoma patients. Diagn Pathol. 2018;13(1):13.
15. Berger AC, Davidson RS, Poitras JK, et al. Clinical impact of a 31-gene expression profile test for cutaneous melanoma in 156 prospectively and consecutively tested patients. Curr Med Res Opin. 2016;32(9):1599-604.
16. Dengel LT, Hickman AW, Slingluff CL. Effect of gene expression profile (GEP) testing on clinical management in 19% of consecutively treated patients with stage IB/IIA melanoma at a single institution. J Clin Oncol. 2017; 35 (suppl; abstr e21080)
17. Schuitevoerder D, Heath M, Cook RW, et al. Impact of Gene Expression Profiling on Decision-Making in Clinically Node Negative Melanoma Patients after Surgical Staging. J Drugs Dermatol. 2018;17(2):196-199.
18. Cook RW, Glazer A, Middlebrook B, et al. Clinical impact of a 31‐gene expression profile test on guidance of sentinel lymph node biopsy, imaging and oncology referral. Pigment Cell Melanoma Res. 2017;30(1):92.
19. Farberg AS, Glazer AM, White R, Rigel DS. Impact of a 31-gene Expression Profiling Test for Cutaneous Melanoma on Dermatologists' Clinical Management Decisions. J Drugs Dermatol. 2017;16(5):428-431.
20. Svoboda RM, Glazer AM, Farberg AS, Rigel DS. Factors Affecting Dermatologists' Use of a 31-Gene Expression Profiling Test as an Adjunct for Predicting Metastatic Risk in Cutaneous Melanoma. J Drugs Dermatol. 2018;17(5):544-547.
21. Gerami P, Cook RW, Wilkinson J, et al. Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res. 2015;21(1):175-83.
22. Gerami P, Cook RW, Russell MC, et al. Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. J Am Acad Dermatol. 2015;72(5):780-5.e3.
23. Cook RW, Covington KR, Monzon FA. Continued evaluation of a 31-gene expression profile to predict metastasis in an expanded cohort of 782 cutaneous melanoma patients. Pigment Cell Melanoma Res. 2017;30:e73.
24. Ferris LK, Farberg AS, Middlebrook B, et al. Identification of high-risk cutaneous melanoma tumors is improved when combining the online American Joint Committee on Cancer Individualized Melanoma Patient Outcome Prediction Tool with a 31-gene expression profile-based classification. J Am Acad Dermatol. 2017;76(5):818-825.e3.
25. Zager JS, Gastman BR, Leachman S, et al. Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. BMC Cancer. 2018;18(1):130.
26. Greenhaw BN, Zitelli JA, Brodland DG. Estimation of Prognosis in Invasive Cutaneous Melanoma: An Independent Study of the Accuracy of a Gene Expression Profile Test. Dermatol Surg. 2018;
27. Hsueh EC, Debloom JR, Lee J, et al. Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test. J Hematol Oncol. 2017;10(1):152.
28. Keller JK, Schwartz T, Lizalek JM, Hsueh EC. Utility of Gene Expression Profiling in Determining Necessity of Sentinel Node Biopsy in Melanoma. Ann Surg Oncol. 2017;24(S1):S148.
29. Huang X, Hewgley WP, Guerrero W, Fleming M. Application of Gene Expression Profiling in the Management of
Cutaneous Melanoma. Ann Surg Oncol. 2017;24(S1):S144.
30. Cook RW, Covington KR, Monzon FA. Prognostic value of non-sentinel lymph node (non-SLN) status and a prognostic 31-gene expression profile (GEP) in stage III cutaneous melanoma patients Pigment Cell Melanoma Res. 2018;31:e144.
31. Keller J, Schwartz T, Lizalek J, Hsueh E. Exploring the Role of Gene Expression Profiling in the Prediction of Non-Sentinel Node Status in Cutaneous Melanoma. Ann Surg Oncol. 2018;24(S1):S67.
32. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Cutaneous Melanoma. 2019.
33. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16. doi:10.1186/1745-6215-8-16.
34. Hayden JA, Van der windt DA, Cartwright JL, Côté P, Bombardier C. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013;158(4):280-6.
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Published
May 8, 2020
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How to Cite
Litchman, G. H., Prado, G., Teplitz, R. W., & Rigel, D. (2020). A Systematic Review and Meta-Analysis of Gene Expression Profiling for Primary Cutaneous Melanoma Prognosis. SKIN The Journal of Cutaneous Medicine, 4(3), 221–237. https://doi.org/10.25251/skin.4.3.3
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