Inflammation and apolipoproteins are potential biomarkers for stratification of cutaneous melanoma patients for immunotherapy and targeted therapy

Max J. Karlsson, Fernanda Costa Svedman, Abdellah Tebani, David Kotol, Veronica Hoiom, Linn Fagerberg, Fredrik Edfors, Mathias Uhlen, Suzanne Egyhazi Brage, Gianluca Maddalo*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Malignant cutaneous melanoma is one of the most common cancers in young adults. During the last decade, targeted and immunotherapies have significantly increased the overall survival of patients with malignant cutaneous melanoma. Nevertheless, disease progression is common, and a lack of predictive biomarkers of patient response to therapy hinders individualized treatment strategies. To address this issue, we performed a longitudinal study using an unbiased proteomics approach to identify and quantify proteins in plasma both before and during treatment from 109 patients treated with either targeted or immunotherapy. Linear modeling and machine learning approaches identified 43 potential prognostic and predictive biomarkers. A reverse correlation between apolipoproteins and proteins related to inflammation was observed. In the immunotherapy group, patients with low pretreatment expression of apolipoproteins and high expression of inflammation markers had shorter progression-free survival. Similarly, increased expression of LDHB during treatment elicited a significant impact on response to immunotherapy. Overall, we identified potential common and treatment-specific biomarkers in malignant cutaneous melanoma, paving the way for clinical use of these biomarkers following validation on a larger cohort.

Original languageEnglish
JournalCancer Research
Volume81
Issue number9
Pages (from-to)2545-2555
ISSN0008-5472
DOIs
Publication statusPublished - 1 May 2021

Bibliographical note

Funding Information:
S. Egyhazi Brage reports grants from Cancer Research Funds from Radiumhem-met and Knut and Alice Wallenberg Foundation during the conduct of the study. G. Maddalo reports grants from Radiumhemmets, O.E. och Edla Johanssons Foundation, and Lars Hiertas Minne during the conduct of the study. No disclosures were reported by the other authors.

Funding Information:
The authors thank Karl-Johan Ekdahl for collection of the plasma samples. The authors thank the oncologists Maria Wolodarski, Hildur Helgadóttir, Giuseppe Masucci, Johan Hansson, Hanna Eriksson, and Johan Falkenius and the nurse Lena Westerberg in helping us with the recruitment of patients for this study. G. Maddalo has been awarded grants from O.E. och Edla Johanssons Vetenskapliga Stiftelse (5310-7132); Swedish Cancer Society (Radiumhemmets; 174212); and Lars Hierta Memorial Foundation. V. Hoiom and S. Egyhazi Brage (co-applicant) have been awarded grants from Cancer Research Funds from Radiumhemmets Forsknings-fonder (194103 and 174153). S. Egyhazi Brage has additionally been awarded grants from KI funds. M. Uhlén has been awarded grants from Knut and Alice Wallenberg Foundation (2019.0341). Knut and Alice Wallenberg Foundation (2013.0093) has supported the collection of samples.

Publisher Copyright:
© 2021 American Association for Cancer Research.

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