Expression and prognostic significance of PDGF ligands and receptors across soft tissue sarcomas

M. Brahmi; T. Lesluyes; A. Dufresne; M. Toulmonde; A. Italiano; O. Mir; A. Le Cesne; T. Valentin; C. Chevreau; S. Bonvalot; N. Penel; J. M. Coindre; S. Le Guellec; F. Le Loarer; M. Karanian; J. Y. Blay; F. Chibon

doi:10.1016/j.esmoop.2020.100037

Expression and prognostic significance of PDGF ligands and receptors across soft tissue sarcomas

M. Brahmi, T. Lesluyes, A. Dufresne, M. Toulmonde, A. Italiano, O. Mir, A. Le Cesne, T. Valentin, C. Chevreau, S. Bonvalot, N. Penel, J. M. Coindre, S. Le Guellec, F. Le Loarer, M. Karanian, J. Y. Blay, F. Chibon

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Résumé

Background: While the anti-PDGFRA antibody olaratumab failed to confirm an impact on survival in unselected advanced soft tissue sarcoma (STS) patients, the level of expression and the prognosis of platelet-derived growth factor (PDGF) receptors and ligands in STS remain unclear. Patients and methods: We analyzed PDGF ligands and receptors' expression levels in a series of 255 patients with different histologies of STS [gastrointestinal stromal tumor (GIST), myxoid liposarcoma (MLPS), sarcoma with complex genomics, synovial sarcoma (SyS)] with Agilent single-color micro-arrays. We explored expression levels as prognostic values in univariate and multivariate analysis using R software (version 3.4.2). Results: Complex patterns of correlation of expression between ligands and receptors were observed for each histotype. PDGFA levels were highest in SyS and lowest in MLPS (P < 4 × 10⁻⁹), PDGFB and C levels were lower in GIST (P < 2 × 10⁻¹⁵ and P < 3 × 10⁻⁹) while PDGFD expression was similar across histological subtypes. PDGF receptor (PDGFR) A expression was lowest in MLPS (P < 0.002), whereas PDGFRB and L expressions were lowest in GIST and SyS (P < 0.0004). Interestingly, high PDGFA expression levels were associated with higher risk of metastasis (P = 0.006), whereas PDGFD levels above average were associated with a reduced risk of metastasis (P = 0.01) in univariate and multivariate analysis. Conclusions: The expression of PDGF ligands and receptors varies across sarcoma histological subtypes. PDGFA and D expression levels independently and inversely correlate with the risk of metastatic relapse.

langue originale	Anglais
Numéro d'article	100037
journal	ESMO Open
Volume	6
Numéro de publication	1
Les DOIs	https://doi.org/10.1016/j.esmoop.2020.100037
état	Publié - 1 févr. 2021

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10.1016/j.esmoop.2020.100037

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Brahmi, M., Lesluyes, T., Dufresne, A., Toulmonde, M., Italiano, A., Mir, O., Le Cesne, A., Valentin, T., Chevreau, C., Bonvalot, S., Penel, N., Coindre, J. M., Le Guellec, S., Le Loarer, F., Karanian, M., Blay, J. Y., & Chibon, F. (2021). Expression and prognostic significance of PDGF ligands and receptors across soft tissue sarcomas. ESMO Open, 6(1), Article 100037. https://doi.org/10.1016/j.esmoop.2020.100037

@article{27ce524d6c87434d946686fe2e25d5b9,

title = "Expression and prognostic significance of PDGF ligands and receptors across soft tissue sarcomas",

abstract = "Background: While the anti-PDGFRA antibody olaratumab failed to confirm an impact on survival in unselected advanced soft tissue sarcoma (STS) patients, the level of expression and the prognosis of platelet-derived growth factor (PDGF) receptors and ligands in STS remain unclear. Patients and methods: We analyzed PDGF ligands and receptors' expression levels in a series of 255 patients with different histologies of STS [gastrointestinal stromal tumor (GIST), myxoid liposarcoma (MLPS), sarcoma with complex genomics, synovial sarcoma (SyS)] with Agilent single-color micro-arrays. We explored expression levels as prognostic values in univariate and multivariate analysis using R software (version 3.4.2). Results: Complex patterns of correlation of expression between ligands and receptors were observed for each histotype. PDGFA levels were highest in SyS and lowest in MLPS (P < 4 × 10−9), PDGFB and C levels were lower in GIST (P < 2 × 10−15 and P < 3 × 10−9) while PDGFD expression was similar across histological subtypes. PDGF receptor (PDGFR) A expression was lowest in MLPS (P < 0.002), whereas PDGFRB and L expressions were lowest in GIST and SyS (P < 0.0004). Interestingly, high PDGFA expression levels were associated with higher risk of metastasis (P = 0.006), whereas PDGFD levels above average were associated with a reduced risk of metastasis (P = 0.01) in univariate and multivariate analysis. Conclusions: The expression of PDGF ligands and receptors varies across sarcoma histological subtypes. PDGFA and D expression levels independently and inversely correlate with the risk of metastatic relapse.",

keywords = "PDGF, PDGFR, expression level, prognostic factor, sarcoma",

author = "M. Brahmi and T. Lesluyes and A. Dufresne and M. Toulmonde and A. Italiano and O. Mir and {Le Cesne}, A. and T. Valentin and C. Chevreau and S. Bonvalot and N. Penel and Coindre, {J. M.} and {Le Guellec}, S. and {Le Loarer}, F. and M. Karanian and Blay, {J. Y.} and F. Chibon",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2021",

month = feb,

day = "1",

doi = "10.1016/j.esmoop.2020.100037",

language = "English",

volume = "6",

journal = "ESMO Open",

issn = "2059-7029",

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Brahmi, M, Lesluyes, T, Dufresne, A, Toulmonde, M, Italiano, A, Mir, O, Le Cesne, A, Valentin, T, Chevreau, C, Bonvalot, S, Penel, N, Coindre, JM, Le Guellec, S, Le Loarer, F, Karanian, M, Blay, JY & Chibon, F 2021, 'Expression and prognostic significance of PDGF ligands and receptors across soft tissue sarcomas', ESMO Open, VOL. 6, Numéro 1, 100037. https://doi.org/10.1016/j.esmoop.2020.100037

TY - JOUR

T1 - Expression and prognostic significance of PDGF ligands and receptors across soft tissue sarcomas

AU - Brahmi, M.

AU - Lesluyes, T.

AU - Dufresne, A.

AU - Toulmonde, M.

AU - Italiano, A.

AU - Mir, O.

AU - Le Cesne, A.

AU - Valentin, T.

AU - Chevreau, C.

AU - Bonvalot, S.

AU - Penel, N.

AU - Coindre, J. M.

AU - Le Guellec, S.

AU - Le Loarer, F.

AU - Karanian, M.

AU - Blay, J. Y.

AU - Chibon, F.

PY - 2021/2/1

Y1 - 2021/2/1

N2 - Background: While the anti-PDGFRA antibody olaratumab failed to confirm an impact on survival in unselected advanced soft tissue sarcoma (STS) patients, the level of expression and the prognosis of platelet-derived growth factor (PDGF) receptors and ligands in STS remain unclear. Patients and methods: We analyzed PDGF ligands and receptors' expression levels in a series of 255 patients with different histologies of STS [gastrointestinal stromal tumor (GIST), myxoid liposarcoma (MLPS), sarcoma with complex genomics, synovial sarcoma (SyS)] with Agilent single-color micro-arrays. We explored expression levels as prognostic values in univariate and multivariate analysis using R software (version 3.4.2). Results: Complex patterns of correlation of expression between ligands and receptors were observed for each histotype. PDGFA levels were highest in SyS and lowest in MLPS (P < 4 × 10−9), PDGFB and C levels were lower in GIST (P < 2 × 10−15 and P < 3 × 10−9) while PDGFD expression was similar across histological subtypes. PDGF receptor (PDGFR) A expression was lowest in MLPS (P < 0.002), whereas PDGFRB and L expressions were lowest in GIST and SyS (P < 0.0004). Interestingly, high PDGFA expression levels were associated with higher risk of metastasis (P = 0.006), whereas PDGFD levels above average were associated with a reduced risk of metastasis (P = 0.01) in univariate and multivariate analysis. Conclusions: The expression of PDGF ligands and receptors varies across sarcoma histological subtypes. PDGFA and D expression levels independently and inversely correlate with the risk of metastatic relapse.

AB - Background: While the anti-PDGFRA antibody olaratumab failed to confirm an impact on survival in unselected advanced soft tissue sarcoma (STS) patients, the level of expression and the prognosis of platelet-derived growth factor (PDGF) receptors and ligands in STS remain unclear. Patients and methods: We analyzed PDGF ligands and receptors' expression levels in a series of 255 patients with different histologies of STS [gastrointestinal stromal tumor (GIST), myxoid liposarcoma (MLPS), sarcoma with complex genomics, synovial sarcoma (SyS)] with Agilent single-color micro-arrays. We explored expression levels as prognostic values in univariate and multivariate analysis using R software (version 3.4.2). Results: Complex patterns of correlation of expression between ligands and receptors were observed for each histotype. PDGFA levels were highest in SyS and lowest in MLPS (P < 4 × 10−9), PDGFB and C levels were lower in GIST (P < 2 × 10−15 and P < 3 × 10−9) while PDGFD expression was similar across histological subtypes. PDGF receptor (PDGFR) A expression was lowest in MLPS (P < 0.002), whereas PDGFRB and L expressions were lowest in GIST and SyS (P < 0.0004). Interestingly, high PDGFA expression levels were associated with higher risk of metastasis (P = 0.006), whereas PDGFD levels above average were associated with a reduced risk of metastasis (P = 0.01) in univariate and multivariate analysis. Conclusions: The expression of PDGF ligands and receptors varies across sarcoma histological subtypes. PDGFA and D expression levels independently and inversely correlate with the risk of metastatic relapse.

KW - PDGF

KW - PDGFR

KW - expression level

KW - prognostic factor

KW - sarcoma

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U2 - 10.1016/j.esmoop.2020.100037

DO - 10.1016/j.esmoop.2020.100037

M3 - Article

C2 - 33524869

AN - SCOPUS:85100619825

SN - 2059-7029

VL - 6

JO - ESMO Open

JF - ESMO Open

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