Golgi Protein GOLM1 Is a Tissue and Urine Biomarker of Prostate Cancer 1 2

Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Neoplasia (New York, N.Y.) (Impact Factor: 4.25). 12/2008; 10(11):1285-94. DOI: 10.1593/neo.08922
Source: PubMed


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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Available from: Debashis Ghosh
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    • "Preoperative serum levels of endoglin correlate with pelvic lymph node metastasis after radical prostatectomy Tissue, serum Prognosis, predictive Wikstrom et al., 2002; Karam et al., 2008 Early prostate cancer antigen (EPCA) PCa-specific nuclear matrix protease PCa patients have higher serum levels of EPCA. The highest preoperative serum levels correspond to metastatic PCa cases Serum Diagnosis, prognosis Zhao et al., 2010; 2012 Golgi membrane protein 1 (GOLM1) Type II Golgi transmembrane protein that collaborates in protein synthesis and transport of protein cargo Up-regulation of GOLM1 expression in PCa compared with normal prostate and BPH tissues Tissue, urine Diagnosis Varambally et al., 2008; Li et al., 2012 To be continued "
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    ABSTRACT: Prostate cancer (PCa) incidence and mortality have decreased in recent years. Nonetheless, it remains one of the most prevalent cancers in men, being a disquieting cause of men's death worldwide. Changes in many cell signaling pathways have a predominant role in the onset, development, and progression of the disease. These include prominent pathways involved in the growth, apoptosis, and angiogenesis of the normal prostate gland, such as androgen and estrogen signaling, and other growth factor signaling pathways. Understanding the foundations of PCa is leading to the discovery of key molecules that could be used to improve patient management. The ideal scenario would be to have a panel of molecules, preferably detectable in body fluids, that are specific and sensitive biomarkers for PCa. In the early stages, androgen deprivation is the gold standard therapy. However, as the cancer progresses, it eventually becomes independent of androgens, and hormonal therapy fails. For this reason, androgen-independent PCa is still a major therapeutic challenge. By disrupting specific protein interactions or manipulating the expression of some key molecules, it might be possible to regulate tumor growth and metastasis formation, avoiding the systemic side effects of current therapies. Clinical trials are already underway to assess the efficacy of molecules specially designed to target key proteins or protein interactions. In this review, we address that recent progress made towards understanding PCa development and the molecular pathways underlying this pathology. We also discuss relevant molecular markers for the management of PCa and new therapeutic challenges.
    Full-text · Article · Jan 2014 · Journal of Zhejiang University SCIENCE B
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    • "Another protein-based candidate for PCa diagnosis is Golgi membrane protein 1 (GOLM1, also known as GP73 and GOLPH2), a transmembrane protein expressed in the epithelial cells of many human tissues [98]. Several studies have recently reported the upregulation of this protein in malignant prostate tissue, suggesting GOLM1 as an additional ancillary positive marker for the tissue-based diagnosis of PCa [99, 100]. On the other hand, PCa tissues, even those of high grade, only rarely express high-molecular-weight cytokeratin (HMWCK, sometimes also referred to as 34βE12, an anti-cytokeratin antibody, clone-specific for high-molecular-weight cytokeratins (cytokeratins 1, 5, 10, and 14)). "
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    ABSTRACT: Prostate cancer (PCa) is the most frequently diagnosed type of cancer in developed countries. The decisive method of diagnosis is based on the results of biopsies, morphologically evaluated to determine the presence or absence of cancer. Although this approach leads to a confident diagnosis in most cases, it can be improved by using the molecular markers present in the tissue. Both miRNAs and proteins are considered excellent candidates for biomarkers in formalin-fixed paraffin-embedded (FFPE) tissues, due to their stability over long periods of time. In the last few years, a concerted effort has been made to develop the necessary tools for their reliable measurement in these types of samples. Furthermore, the use of these kinds of markers may also help in establishing tumor grade and aggressiveness, as well as predicting the possible outcomes in each particular case for the different treatments available. This would aid clinicians in the decision-making process. In this review, we attempt to summarize and discuss the potential use of microRNA and protein profiles in FFPE tissue samples as markers to better predict PCa diagnosis, progression, and response to therapy.
    Full-text · Article · Nov 2013
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    • "Liver disease, such as virus infection and cirrhosis, could up-regulate the expression of GP73 in hepatocytes [1,7,8]. Recent studies showed that GP73 was over-expressed in several cancers, such as hepatocellular carcinomas [9-11], bile duct carcinomas [11], lung adenocarcinomas [12], prostate cancer [13,14] and seminomas [15]. The expression of GP73 in renal cancer is much more comprehensive. "
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    ABSTRACT: Background Golgi protein 73 (GP73) is a type II Golgi transmembrane protein. It is over-expressed in several cancers, including hepatocellular carcinomas, bile duct carcinomas, lung cancer and prostate cancer. However, there are few reports of GP73 in gastric cancer. This study is aimed at investigating the expression of GP73 and its relationship with clinical pathological characters in gastric cancer. Methods GP73 mRNA level was determined by quantitative real-time RT-PCR in 41 pairs of matched gastric tumorous tissues and adjacent non-tumorous mucosal tissues. Western blotting was also performed to detect the GP73 protein level. GP73 protein expression was analyzed by immunohistochemistry in 52 clinically characterized gastric cancer patients and 10 non-tumorous gastric mucosal tissue controls. Results The mRNA and protein level of GP73 were significantly down-regulated in gastric tumorous tissues compared with the non-tumorous mucosal tissues. In non-tumorous mucosa, strong diffuse cytoplasmic staining can be seen in cells located at the surface of the glandular and foveolar compartment; while in tumorous tissues, the staining was much weaker or even absent, and mainly in a semi-granular dot-like staining pattern. The expression level of GP73 protein was associated with patients’ gender and tumor differentiation. Conclusions GP73 was normally expressed in non-tumorous gastric mucosa and down-regulated in gastric cancer. Its expression in gastric cancer was correlated with tumor differentiation.
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