Golgi protein GOLM1 is a tissue and urine biomarker of prostate cancer

Sooryanarayana Varambally; Bharathi Laxman; Rohit Mehra; Qi Cao; Saravana M. Dhanasekaran; Scott A. Tomlins; Jill Granger; Adaikkalam Vellaichamy; Arun Sreekumar; Jianjun Yu; Wenjuan Gu; Ronglai Shen; Debashis Ghosh; Lorinda M. Wright; Raleigh D. Kladney; Rainer Kuefer; Mark A. Rubin; Claus J. Fimmel; Arul M. Chinnaiyan

doi:10.1593/neo.08922

Golgi protein GOLM1 is a tissue and urine biomarker of prostate cancer

Sooryanarayana Varambally^*, Bharathi Laxman, Rohit Mehra, Qi Cao, Saravana M. Dhanasekaran, Scott A. Tomlins, Jill Granger, Adaikkalam Vellaichamy, Arun Sreekumar, Jianjun Yu, Wenjuan Gu, Ronglai Shen, Debashis Ghosh, Lorinda M. Wright, Raleigh D. Kladney, Rainer Kuefer, Mark A. Rubin, Claus J. Fimmel, Arul M. Chinnaiyan

^*Corresponding author for this work

Urology

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

92 Scopus citations

Abstract

Prostate cancer is the most common type of tumor found in American men and is the second leading cause of cancer death in males. To identify biomarkers that distinguish prostate cancer from normal, we compared multiple gene expression profiling studies. Through meta-analysis of expression array data from multiple prostate cancer studies, we identified GOLM1 (Golgi membrane protein 1, Golm 1) as consistently up-regulated in clinically localized prostate cancer. This observation was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and validated at the protein level by immunoblot assay and immunohistochemistry. Prostate epithelial cells were identified as the cellular source of GOLM1 expression using laser capture microdissection. Immunohistochemical staining localized the GOLM1 signal to the subapical cytoplasmic region, typical of a Golgi distribution. Surprisingly, GOLM1 immunoreactivity was detected in the supernatants of prostate cell lines and in the urine of patients with prostate cancer. The mechanism by which intact GOLM1 might be released from cells has not yet been elucidated. GOLM1 transcript levels were measured in urine sediments using quantitative PCR on a cohort of patients presenting for biopsy or radical prostatectomy. We found that urinary GOLM1 mRNA levels were a significant predictor of prostate cancer. Further, GOLM1 outperformed serum prostate-specific antigen (PSA) in detecting prostate cancer. The area under the receiver-operating characteristic curve was 0.622 for GOLM1 (P = .0009) versus 0.495 for serum PSA (P = .902). Our data indicating the up-regulation of GOLM1 expression and its appearance in patients' urine suggest GOLM1 as a potential novel biomarker for clinically localized prostate cancer.

Original language	English (US)
Pages (from-to)	1285-1294
Number of pages	10
Journal	Neoplasia
Volume	10
Issue number	11
DOIs	https://doi.org/10.1593/neo.08922
State	Published - Nov 2008

Funding

Abbreviations: Golm1, Golgi membrane protein 1; PSA, prostate-specific antigen; PIN, prostatic intraepithelial neoplasia; BPH, benign prostatic hyperplasia; LCM, laser capture microdissection Address all correspondence to: Arul M. Chinnaiyan, MD, PhD, Department of Pathology, University of Michigan Medical School, 1400 E. Medical Center Dr. 5316 CCGC, Ann Arbor, MI 48109-0602. E-mail: [email protected]; and Sooryanarayana Varambally, PhD, Department of Pathology, University of Michigan Medical School, 1400 E. Medical Center Dr. 5430 CCGC, Ann Arbor, MI 48109. E-mail: [email protected] 1This research was supported in part by the National Institutes of Health Prostate SPORE P50 CA69568 (to A.M.C.); Department of Defense Grants PC040517 (to R.M.), PC051081 (to A.M.C. and S.V.). C.J.F. was supported by a VA Merit Review. 2This article refers to supplementary materials, which are designated by Tables W1 and W2 and are available online at www.neoplasia.com. Received 4 August 2008; Revised 2 September 2008; Accepted 2 September 2008 Copyright © 2008 Neoplasia Press, Inc. All rights reserved 1522-8002/08/$25.00 DOI 10.1593/neo.08922

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Cancer Research

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10.1593/neo.08922

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Varambally, S., Laxman, B., Mehra, R., Cao, Q., Dhanasekaran, S. M., Tomlins, S. A., Granger, J., Vellaichamy, A., Sreekumar, A., Yu, J., Gu, W., Shen, R., Ghosh, D., Wright, L. M., Kladney, R. D., Kuefer, R., Rubin, M. A., Fimmel, C. J., & Chinnaiyan, A. M. (2008). Golgi protein GOLM1 is a tissue and urine biomarker of prostate cancer. Neoplasia, 10(11), 1285-1294. https://doi.org/10.1593/neo.08922

@article{e08c57172b694e018072e9f8dafc3291,

title = "Golgi protein GOLM1 is a tissue and urine biomarker of prostate cancer",

abstract = "Prostate cancer is the most common type of tumor found in American men and is the second leading cause of cancer death in males. To identify biomarkers that distinguish prostate cancer from normal, we compared multiple gene expression profiling studies. Through meta-analysis of expression array data from multiple prostate cancer studies, we identified GOLM1 (Golgi membrane protein 1, Golm 1) as consistently up-regulated in clinically localized prostate cancer. This observation was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and validated at the protein level by immunoblot assay and immunohistochemistry. Prostate epithelial cells were identified as the cellular source of GOLM1 expression using laser capture microdissection. Immunohistochemical staining localized the GOLM1 signal to the subapical cytoplasmic region, typical of a Golgi distribution. Surprisingly, GOLM1 immunoreactivity was detected in the supernatants of prostate cell lines and in the urine of patients with prostate cancer. The mechanism by which intact GOLM1 might be released from cells has not yet been elucidated. GOLM1 transcript levels were measured in urine sediments using quantitative PCR on a cohort of patients presenting for biopsy or radical prostatectomy. We found that urinary GOLM1 mRNA levels were a significant predictor of prostate cancer. Further, GOLM1 outperformed serum prostate-specific antigen (PSA) in detecting prostate cancer. The area under the receiver-operating characteristic curve was 0.622 for GOLM1 (P = .0009) versus 0.495 for serum PSA (P = .902). Our data indicating the up-regulation of GOLM1 expression and its appearance in patients' urine suggest GOLM1 as a potential novel biomarker for clinically localized prostate cancer.",

author = "Sooryanarayana Varambally and Bharathi Laxman and Rohit Mehra and Qi Cao and Dhanasekaran, {Saravana M.} and Tomlins, {Scott A.} and Jill Granger and Adaikkalam Vellaichamy and Arun Sreekumar and Jianjun Yu and Wenjuan Gu and Ronglai Shen and Debashis Ghosh and Wright, {Lorinda M.} and Kladney, {Raleigh D.} and Rainer Kuefer and Rubin, {Mark A.} and Fimmel, {Claus J.} and Chinnaiyan, {Arul M.}",

note = "Funding Information: Abbreviations: Golm1, Golgi membrane protein 1; PSA, prostate-specific antigen; PIN, prostatic intraepithelial neoplasia; BPH, benign prostatic hyperplasia; LCM, laser capture microdissection Address all correspondence to: Arul M. Chinnaiyan, MD, PhD, Department of Pathology, University of Michigan Medical School, 1400 E. Medical Center Dr. 5316 CCGC, Ann Arbor, MI 48109-0602. E-mail: [email protected]; and Sooryanarayana Varambally, PhD, Department of Pathology, University of Michigan Medical School, 1400 E. Medical Center Dr. 5430 CCGC, Ann Arbor, MI 48109. E-mail: [email protected] 1This research was supported in part by the National Institutes of Health Prostate SPORE P50 CA69568 (to A.M.C.); Department of Defense Grants PC040517 (to R.M.), PC051081 (to A.M.C. and S.V.). C.J.F. was supported by a VA Merit Review. 2This article refers to supplementary materials, which are designated by Tables W1 and W2 and are available online at www.neoplasia.com. Received 4 August 2008; Revised 2 September 2008; Accepted 2 September 2008 Copyright {\textcopyright} 2008 Neoplasia Press, Inc. All rights reserved 1522-8002/08/$25.00 DOI 10.1593/neo.08922",

year = "2008",

month = nov,

doi = "10.1593/neo.08922",

language = "English (US)",

volume = "10",

pages = "1285--1294",

journal = "Neoplasia",

issn = "1522-8002",

publisher = "Elsevier Inc.",

number = "11",

}

Varambally, S, Laxman, B, Mehra, R, Cao, Q, Dhanasekaran, SM, Tomlins, SA, Granger, J, Vellaichamy, A, Sreekumar, A, Yu, J, Gu, W, Shen, R, Ghosh, D, Wright, LM, Kladney, RD, Kuefer, R, Rubin, MA, Fimmel, CJ & Chinnaiyan, AM 2008, 'Golgi protein GOLM1 is a tissue and urine biomarker of prostate cancer', Neoplasia, vol. 10, no. 11, pp. 1285-1294. https://doi.org/10.1593/neo.08922

TY - JOUR

T1 - Golgi protein GOLM1 is a tissue and urine biomarker of prostate cancer

AU - Varambally, Sooryanarayana

AU - Laxman, Bharathi

AU - Mehra, Rohit

AU - Cao, Qi

AU - Dhanasekaran, Saravana M.

AU - Tomlins, Scott A.

AU - Granger, Jill

AU - Vellaichamy, Adaikkalam

AU - Sreekumar, Arun

AU - Yu, Jianjun

AU - Gu, Wenjuan

AU - Shen, Ronglai

AU - Ghosh, Debashis

AU - Wright, Lorinda M.

AU - Kladney, Raleigh D.

AU - Kuefer, Rainer

AU - Rubin, Mark A.

AU - Fimmel, Claus J.

AU - Chinnaiyan, Arul M.

N1 - Funding Information: Abbreviations: Golm1, Golgi membrane protein 1; PSA, prostate-specific antigen; PIN, prostatic intraepithelial neoplasia; BPH, benign prostatic hyperplasia; LCM, laser capture microdissection Address all correspondence to: Arul M. Chinnaiyan, MD, PhD, Department of Pathology, University of Michigan Medical School, 1400 E. Medical Center Dr. 5316 CCGC, Ann Arbor, MI 48109-0602. E-mail: [email protected]; and Sooryanarayana Varambally, PhD, Department of Pathology, University of Michigan Medical School, 1400 E. Medical Center Dr. 5430 CCGC, Ann Arbor, MI 48109. E-mail: [email protected] 1This research was supported in part by the National Institutes of Health Prostate SPORE P50 CA69568 (to A.M.C.); Department of Defense Grants PC040517 (to R.M.), PC051081 (to A.M.C. and S.V.). C.J.F. was supported by a VA Merit Review. 2This article refers to supplementary materials, which are designated by Tables W1 and W2 and are available online at www.neoplasia.com. Received 4 August 2008; Revised 2 September 2008; Accepted 2 September 2008 Copyright © 2008 Neoplasia Press, Inc. All rights reserved 1522-8002/08/$25.00 DOI 10.1593/neo.08922

PY - 2008/11

Y1 - 2008/11

N2 - Prostate cancer is the most common type of tumor found in American men and is the second leading cause of cancer death in males. To identify biomarkers that distinguish prostate cancer from normal, we compared multiple gene expression profiling studies. Through meta-analysis of expression array data from multiple prostate cancer studies, we identified GOLM1 (Golgi membrane protein 1, Golm 1) as consistently up-regulated in clinically localized prostate cancer. This observation was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and validated at the protein level by immunoblot assay and immunohistochemistry. Prostate epithelial cells were identified as the cellular source of GOLM1 expression using laser capture microdissection. Immunohistochemical staining localized the GOLM1 signal to the subapical cytoplasmic region, typical of a Golgi distribution. Surprisingly, GOLM1 immunoreactivity was detected in the supernatants of prostate cell lines and in the urine of patients with prostate cancer. The mechanism by which intact GOLM1 might be released from cells has not yet been elucidated. GOLM1 transcript levels were measured in urine sediments using quantitative PCR on a cohort of patients presenting for biopsy or radical prostatectomy. We found that urinary GOLM1 mRNA levels were a significant predictor of prostate cancer. Further, GOLM1 outperformed serum prostate-specific antigen (PSA) in detecting prostate cancer. The area under the receiver-operating characteristic curve was 0.622 for GOLM1 (P = .0009) versus 0.495 for serum PSA (P = .902). Our data indicating the up-regulation of GOLM1 expression and its appearance in patients' urine suggest GOLM1 as a potential novel biomarker for clinically localized prostate cancer.

AB - Prostate cancer is the most common type of tumor found in American men and is the second leading cause of cancer death in males. To identify biomarkers that distinguish prostate cancer from normal, we compared multiple gene expression profiling studies. Through meta-analysis of expression array data from multiple prostate cancer studies, we identified GOLM1 (Golgi membrane protein 1, Golm 1) as consistently up-regulated in clinically localized prostate cancer. This observation was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and validated at the protein level by immunoblot assay and immunohistochemistry. Prostate epithelial cells were identified as the cellular source of GOLM1 expression using laser capture microdissection. Immunohistochemical staining localized the GOLM1 signal to the subapical cytoplasmic region, typical of a Golgi distribution. Surprisingly, GOLM1 immunoreactivity was detected in the supernatants of prostate cell lines and in the urine of patients with prostate cancer. The mechanism by which intact GOLM1 might be released from cells has not yet been elucidated. GOLM1 transcript levels were measured in urine sediments using quantitative PCR on a cohort of patients presenting for biopsy or radical prostatectomy. We found that urinary GOLM1 mRNA levels were a significant predictor of prostate cancer. Further, GOLM1 outperformed serum prostate-specific antigen (PSA) in detecting prostate cancer. The area under the receiver-operating characteristic curve was 0.622 for GOLM1 (P = .0009) versus 0.495 for serum PSA (P = .902). Our data indicating the up-regulation of GOLM1 expression and its appearance in patients' urine suggest GOLM1 as a potential novel biomarker for clinically localized prostate cancer.

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Golgi protein GOLM1 is a tissue and urine biomarker of prostate cancer

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