Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer

Carissa E. Chu; Mohammed Alshalalfa; Martin Sjöström; Shuang G. Zhao; Yang Liu; Jonathan Chou; Annika Herlemann; Brandon Mahal; Amar U. Kishan; Daniel E. Spratt; Matthew Cooperberg; Eric Small; Anthony Wong; Sima Porten; Thomas A. Hope; Ashley E. Ross; Elai Davicioni; Paul Nguyen; R. Jeffrey Karnes; Peter R. Carroll; Edward Schaeffer; Felix Y. Feng

doi:10.1016/j.eururo.2021.03.017

Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer

Carissa E. Chu, Mohammed Alshalalfa, Martin Sjöström, Shuang G. Zhao, Yang Liu, Jonathan Chou, Annika Herlemann, Brandon Mahal, Amar U. Kishan, Daniel E. Spratt, Matthew Cooperberg, Eric Small, Anthony Wong, Sima Porten, Thomas A. Hope, Ashley E. Ross, Elai Davicioni, Paul Nguyen, R. Jeffrey Karnes, Peter R. CarrollEdward Schaeffer, Felix Y. Feng

Urology

Research output: Contribution to journal › Article › peer-review

Abstract

¹⁸F-Fluciclovine-based positron emission tomography (PET) imaging is recommended in the USA for biochemical recurrence (BCR) after prostate cancer treatment. However, prostate-specific membrane antigen (PSMA)-based PET imaging is more common worldwide, supported by international guidelines, and is now approved by the Food and Drug Administration in the USA for initial staging of primary prostate cancer. Little is known about the molecular profiles of lesions detected by PSMA-targeted PET/computed tomography (CT) versus ¹⁸F-fluciclovine PET/CT. We examined the expression of PSMA (FOLH1) and the fluciclovine transporter genes LAT1–4 and ASCT1/2 in a combined cohort of more than 18 000 radical prostatectomy specimens and their associations with clinical outcomes. Expression of PSMA and all but one fluciclovine transporter gene was higher in prostate cancer than in benign tissue. PSMA expression was associated with Gleason score (GS) ≥8 and lymph node involvement (LNI), and had a positive linear correlation with Decipher risk score. By contrast, expression of the fluciclovine transporters LAT2, LAT3, and ASCT2 was negatively associated with GS ≥ 8, LNI, and high Decipher score. The top decile of PSMA expression was associated with poorest metastasis-free survival (MFS), while the bottom deciles of LAT3 and ASCT2 expression were associated with poorest MFS. Patient summary: We measured the expression of genes that encode the targets for two different radiotracers in PET (positron emission tomography) scans of the prostate. We found that PSMA gene expression (PSMA-based tracer) is associated with worse clinical outcomes, while expression of ASCT2, LAT2, and LAT3 genes (fluciclovine tracer) is associated with better outcomes.

Original language	English (US)
Pages (from-to)	717-721
Number of pages	5
Journal	European urology
Volume	79
Issue number	6
DOIs	https://doi.org/10.1016/j.eururo.2021.03.017
State	Published - Jun 2021

Keywords

Fluciclovine transporter
Gene expression
Nuclear imaging
Prostate cancer
Prostate-specific membrane antigen

ASJC Scopus subject areas

Urology

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10.1016/j.eururo.2021.03.017

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Chu, C. E., Alshalalfa, M., Sjöström, M., Zhao, S. G., Liu, Y., Chou, J., Herlemann, A., Mahal, B., Kishan, A. U., Spratt, D. E., Cooperberg, M., Small, E., Wong, A., Porten, S., Hope, T. A., Ross, A. E., Davicioni, E., Nguyen, P., Karnes, R. J., ... Feng, F. Y. (2021). Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer. European urology, 79(6), 717-721. https://doi.org/10.1016/j.eururo.2021.03.017

Chu, CE, Alshalalfa, M, Sjöström, M, Zhao, SG, Liu, Y, Chou, J, Herlemann, A, Mahal, B, Kishan, AU, Spratt, DE, Cooperberg, M, Small, E, Wong, A, Porten, S, Hope, TA, Ross, AE, Davicioni, E, Nguyen, P, Karnes, RJ, Carroll, PR, Schaeffer, E & Feng, FY 2021, 'Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer', European urology, vol. 79, no. 6, pp. 717-721. https://doi.org/10.1016/j.eururo.2021.03.017

@article{20e3d97b9d99411eb61250888367de7b,

title = "Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer",

abstract = "18F-Fluciclovine-based positron emission tomography (PET) imaging is recommended in the USA for biochemical recurrence (BCR) after prostate cancer treatment. However, prostate-specific membrane antigen (PSMA)-based PET imaging is more common worldwide, supported by international guidelines, and is now approved by the Food and Drug Administration in the USA for initial staging of primary prostate cancer. Little is known about the molecular profiles of lesions detected by PSMA-targeted PET/computed tomography (CT) versus 18F-fluciclovine PET/CT. We examined the expression of PSMA (FOLH1) and the fluciclovine transporter genes LAT1–4 and ASCT1/2 in a combined cohort of more than 18 000 radical prostatectomy specimens and their associations with clinical outcomes. Expression of PSMA and all but one fluciclovine transporter gene was higher in prostate cancer than in benign tissue. PSMA expression was associated with Gleason score (GS) ≥8 and lymph node involvement (LNI), and had a positive linear correlation with Decipher risk score. By contrast, expression of the fluciclovine transporters LAT2, LAT3, and ASCT2 was negatively associated with GS ≥ 8, LNI, and high Decipher score. The top decile of PSMA expression was associated with poorest metastasis-free survival (MFS), while the bottom deciles of LAT3 and ASCT2 expression were associated with poorest MFS. Patient summary: We measured the expression of genes that encode the targets for two different radiotracers in PET (positron emission tomography) scans of the prostate. We found that PSMA gene expression (PSMA-based tracer) is associated with worse clinical outcomes, while expression of ASCT2, LAT2, and LAT3 genes (fluciclovine tracer) is associated with better outcomes.",

keywords = "Fluciclovine transporter, Gene expression, Nuclear imaging, Prostate cancer, Prostate-specific membrane antigen",

author = "Chu, {Carissa E.} and Mohammed Alshalalfa and Martin Sj{\"o}str{\"o}m and Zhao, {Shuang G.} and Yang Liu and Jonathan Chou and Annika Herlemann and Brandon Mahal and Kishan, {Amar U.} and Spratt, {Daniel E.} and Matthew Cooperberg and Eric Small and Anthony Wong and Sima Porten and Hope, {Thomas A.} and Ross, {Ashley E.} and Elai Davicioni and Paul Nguyen and Karnes, {R. Jeffrey} and Carroll, {Peter R.} and Edward Schaeffer and Feng, {Felix Y.}",

note = "Publisher Copyright: {\textcopyright} 2021 European Association of Urology",

year = "2021",

month = jun,

doi = "10.1016/j.eururo.2021.03.017",

language = "English (US)",

volume = "79",

pages = "717--721",

journal = "European urology",

issn = "0302-2838",

publisher = "Elsevier",

number = "6",

}

TY - JOUR

T1 - Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer

AU - Chu, Carissa E.

AU - Alshalalfa, Mohammed

AU - Sjöström, Martin

AU - Zhao, Shuang G.

AU - Liu, Yang

AU - Chou, Jonathan

AU - Herlemann, Annika

AU - Mahal, Brandon

AU - Kishan, Amar U.

AU - Spratt, Daniel E.

AU - Cooperberg, Matthew

AU - Small, Eric

AU - Wong, Anthony

AU - Porten, Sima

AU - Hope, Thomas A.

AU - Ross, Ashley E.

AU - Davicioni, Elai

AU - Nguyen, Paul

AU - Karnes, R. Jeffrey

AU - Carroll, Peter R.

AU - Schaeffer, Edward

AU - Feng, Felix Y.

PY - 2021/6

Y1 - 2021/6

N2 - 18F-Fluciclovine-based positron emission tomography (PET) imaging is recommended in the USA for biochemical recurrence (BCR) after prostate cancer treatment. However, prostate-specific membrane antigen (PSMA)-based PET imaging is more common worldwide, supported by international guidelines, and is now approved by the Food and Drug Administration in the USA for initial staging of primary prostate cancer. Little is known about the molecular profiles of lesions detected by PSMA-targeted PET/computed tomography (CT) versus 18F-fluciclovine PET/CT. We examined the expression of PSMA (FOLH1) and the fluciclovine transporter genes LAT1–4 and ASCT1/2 in a combined cohort of more than 18 000 radical prostatectomy specimens and their associations with clinical outcomes. Expression of PSMA and all but one fluciclovine transporter gene was higher in prostate cancer than in benign tissue. PSMA expression was associated with Gleason score (GS) ≥8 and lymph node involvement (LNI), and had a positive linear correlation with Decipher risk score. By contrast, expression of the fluciclovine transporters LAT2, LAT3, and ASCT2 was negatively associated with GS ≥ 8, LNI, and high Decipher score. The top decile of PSMA expression was associated with poorest metastasis-free survival (MFS), while the bottom deciles of LAT3 and ASCT2 expression were associated with poorest MFS. Patient summary: We measured the expression of genes that encode the targets for two different radiotracers in PET (positron emission tomography) scans of the prostate. We found that PSMA gene expression (PSMA-based tracer) is associated with worse clinical outcomes, while expression of ASCT2, LAT2, and LAT3 genes (fluciclovine tracer) is associated with better outcomes.

AB - 18F-Fluciclovine-based positron emission tomography (PET) imaging is recommended in the USA for biochemical recurrence (BCR) after prostate cancer treatment. However, prostate-specific membrane antigen (PSMA)-based PET imaging is more common worldwide, supported by international guidelines, and is now approved by the Food and Drug Administration in the USA for initial staging of primary prostate cancer. Little is known about the molecular profiles of lesions detected by PSMA-targeted PET/computed tomography (CT) versus 18F-fluciclovine PET/CT. We examined the expression of PSMA (FOLH1) and the fluciclovine transporter genes LAT1–4 and ASCT1/2 in a combined cohort of more than 18 000 radical prostatectomy specimens and their associations with clinical outcomes. Expression of PSMA and all but one fluciclovine transporter gene was higher in prostate cancer than in benign tissue. PSMA expression was associated with Gleason score (GS) ≥8 and lymph node involvement (LNI), and had a positive linear correlation with Decipher risk score. By contrast, expression of the fluciclovine transporters LAT2, LAT3, and ASCT2 was negatively associated with GS ≥ 8, LNI, and high Decipher score. The top decile of PSMA expression was associated with poorest metastasis-free survival (MFS), while the bottom deciles of LAT3 and ASCT2 expression were associated with poorest MFS. Patient summary: We measured the expression of genes that encode the targets for two different radiotracers in PET (positron emission tomography) scans of the prostate. We found that PSMA gene expression (PSMA-based tracer) is associated with worse clinical outcomes, while expression of ASCT2, LAT2, and LAT3 genes (fluciclovine tracer) is associated with better outcomes.

KW - Fluciclovine transporter

KW - Gene expression

KW - Nuclear imaging

KW - Prostate cancer

KW - Prostate-specific membrane antigen

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ER -

Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer

Abstract

Keywords

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