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. 2023 Mar 23;13(1):43.
doi: 10.1038/s41408-023-00817-7.

Prognostic value of extracellular matrix gene mutations and expression in multiple myeloma

Marietheres Evers  1 , Martin Schreder  2   3 , Thorsten Stühmer  4 , Franziska Jundt  2   4 , Regina Ebert  5 , Tanja Nicole Hartmann  6 , Michael Altenbuchinger  7 , Martina Rudelius  1   8 , Martin Kuric  5 , Wyonna Darleen Rindt  2 , Torsten Steinbrunn  2   9 , Christian Langer  10 , Sofia Catalina Heredia-Guerrero  1 , Hermann Einsele  2 , Ralf Christian Bargou  4 , Andreas Rosenwald  1   4 , Ellen Leich  11   12
Affiliations

Prognostic value of extracellular matrix gene mutations and expression in multiple myeloma

Marietheres Evers et al. Blood Cancer J. .
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. ECM gene mutations as prognostic markers in MM.
A Representation of the mutation status of patients with and without mutations in adhesion genes (blue), ECM genes (green) (ECMmut and ECMWT) and the TMB (yellow). Further, cMyc protein expression (orange), del17p status (red), overall high-risk status at diagnosis (a.d.) (light pink) and at biopsy (a.b.) (dark pink) and information on the presence of extramedullary disease (EMD) (salmon) are shown. Individual patients are separated by small gaps. B STRING network analysis of mutated adhesion genes in our WES study cohort revealed clusters in integrin, collagen, laminin and metalloproteinase genes (ADAMs, ADAMTS). C ECM genes contained significantly more SNVs relative to the protein length than other protein-coding genes within the MMRF WES dataset. Non-protein-coding genes were excluded from the analysis (Table S1). Data shown is median with 95% CI. Statistical test was Mann-Whitney-U. D Visual representation of domains and structure of proteins encoded by the three ECM genes most recurrently affected by mutations: COL6A3, LAMA1 and ADAMTS20. For all other ECM molecules and more information on mutations see Fig. S1 and Table S3. Information on protein structure and domains was obtained from the Uniprot knowledgebase. E PFS was significantly shorter (median PFS 938.0 vs. 1176.0 days) in ECMmut patients compared to ECMWT patients. Comparisons were performed using the Kaplan Meier method and Log Rank test. Table shows Hazard ratios (HR) for high TMB and ECM mutations calculated using the Cox proportional hazards model in SPSS. F Mutations in ADAM18 and ADAMTS13 were associated with a significantly shorter OS (median 349.0 days vs. not reached and 154.0 vs. not reached, respectively). Tables below Kaplan Meier plots show HRs calculated using the Cox proportional hazards model for high TMB and ADAM18mut or ADAMTS13mut. Graphs were created using GraphPad Prism 9.
Fig. 2
Fig. 2. ECM gene expression levels as prognostic markers in MM.
Gene expression of integrin (A), laminin (B), ADAM (C), ADAMTS (D) and collagen (E) genes determined by RNA sequencing of 921 samples from 806 patients of the MMRF cohort. Data shown is median transcripts per kilobase million (TPM) with 95% CI. F Summary of selected genes where a GE higher than the mean or median is significantly associated with PFS and/or OS. Comparisons were performed using the Kaplan Meier method and Log Rank test. P values were adjusted for multiple hypotheses using the Benjamini-Hochberg (BH) correction in R. For Kaplan Meier plots see Fig. S2. DGIdb was used to reveal druggable targets. G Exemplary Kaplan Meier plots comparing PFS and OS of patients with a high (>median) or low (<median) ADAM9 GE. Statistical test was Log Rank test. Graphs were created using GraphPad Prism 9.
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References

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