Glypican-1 as a Biomarker for Prostate Cancer: Isolation and Characterization

Truong, Quach; Justiniano, Irene; Nocon, Aline L.; Soon, Julie; Wissmueller, Sandra; Campbell, Douglas Houghton; Walsh, Bradley J.

doi:10.7150/jca.14645

Cited by 44 publications

(66 citation statements)

References 35 publications

(36 reference statements)

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“…Because of the essential roles of GPC1 in the pathways of heparin binding growth factors and the TGF‐ β families, Wnt and Shh, it appears that GPC1 participates in the carcinogenesis of several tumors. Except for PDAC, the overexpression of GPC1 has been observed in the tumor tissues of gliomas, ameloblastomas, prostate cancer and esophageal squamous cell carcinoma (ESCC) . However, contradictory results were observed in colorectal cancer and breast cancer .…”

Section: Discussionmentioning

confidence: 99%

Elevated glypican‐1 expression is associated with an unfavorable prognosis in pancreatic ductal adenocarcinoma

et al. 2017

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Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer in humans, with a 5-year survival rate of <5%. Recently, glypican-1 (GPC1)-expressing circulating exosomes were found to be a promising diagnostic tool for PDAC. However, the aberrant expression of GPC1 has not been systematically evaluated in large-scale clinical samples of PDAC. Here, we performed a comprehensive analysis of GPC1 mRNA and protein expression features. Included in this study were 178 PDAC patients from the cancer genome atlas (TCGA) and 186 subjects whose tissues were used in immunohistochemical staining assays. We demonstrated that GPC1 mRNA was silenced in normal pancreata; however, it was re-expressed in PDAC tissues probably because of the promoter hypomethylation. The GPC1 protein was barely expressed in the normal and adjacent noncancerous pancreata. In tumor tissues, 59.7% (111/186) of the detected samples showed positive expression. Notably, GPC1 was elevated in 63.6% (34/55) of early stage cases. High levels of GPC1 were associated with poorer differentiation and larger tumor diameters. Kaplan-Meier analysis showed a significant difference in overall survival between the groups categorized by GPC1 expression (P = 0.0028). Multivariate analyses indicated that GPC1 was a significant risk factor for poor overall survival with a 1.82-fold increase in the hazard ratio (P = 0.0022). In conclusion, during pancreatic tumorigenesis, GPC1 was ectopically expressed and served as an independent poor prognostic factor. Our findings highlighted the alluring prospect of GPC1 as an early diagnostic and prognostic marker as well as a therapeutic target for PDAC. Cancer Medicine Open Access 1182

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Section: Discussionmentioning

confidence: 99%

Elevated glypican‐1 expression is associated with an unfavorable prognosis in pancreatic ductal adenocarcinoma

et al. 2017

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“…In human diseases, GPC1 exosomes have been investigated as a specific biomarker for the early diagnosis of pancreatic cancer in recent years . Other GPC1‐related diseases include breast cancer, esophageal squamous cell carcinoma, ameloblastoma, prostate cancer, neuroendocrine tumors, etc. The association between GPC2 and human diseases has not been clarified to date.…”

Section: Structure and Expression Of Glypicansmentioning

confidence: 99%

Glypican‐3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment

Zhou

Shang

et al. 2017

Medicinal Research Reviews

274

192

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Liver cancer is the second leading cause of cancer-related deaths, and hepatocellular carcinoma (HCC) is the most common type. Therefore, molecular targets are urgently required for the early detection of HCC and the development of novel therapeutic approaches. Glypican-3 (GPC3), an oncofetal proteoglycan anchored to the cell membrane, is normally detected in the fetal liver but not in the healthy adult liver. However, in HCC patients, GPC3 is overexpressed at both the gene and protein levels, and its expression predicts a poor prognosis. Mechanistic studies have revealed that GPC3 functions in HCC progression by binding to molecules such as Wnt signaling proteins and growth factors. Moreover, GPC3 has been used as a target for molecular imaging and therapeutic intervention in HCC. To date, GPC3-targeted magnetic resonance imaging, positron emission tomography, and near-infrared imaging have been investigated for early HCC detection, and various immunotherapeutic protocols targeting GPC3 have been developed, including the use of humanized anti-GPC3 cytotoxic antibodies, treatment with peptide/DNA vaccines, immunotoxin therapies, and genetic therapies. In this review, we summarize the current knowledge regarding the structure, function, and biology of GPC3 with a focus on its clinical potential as a diagnostic molecule and a therapeutic target in HCC immunotherapy.

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“…All men were Caucasian with the exception of 3 who were African American. Biomarker levels were determined using a plate based ELISA for Glypican-1 (GPC-1) 2 and a bead-based MIA assay for the other markers.…”

Section: Methodsmentioning

confidence: 99%

A multivariate index analyte (MIA) assay for differentiating aggressive from nonaggressive prostate cancer.

Campbell¹,

Velonas²,

Soon³

et al. 2017

JCO

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e588 Background: Biomarkers that can assist clinicians and patients to proceed when PSA and /or DRE are equivocal. Such biomarkers should establish both sensitivity and specificity for prostate cancer detection in order to improve go-forward decisions to perform prostate biopsy. Following the successful use of a three-protein marker panel to increase the specificity of prostate cancer detection1 we have now used the same technology to examine whether an MIA assay can assist in differentiating aggressive from non-aggressive cancer in prostate cancer patients. Methods: Samples from patients with either aggressive prostate cancer or non- aggressive prostate cancer were obtained from two sources. The cohort criteria comprised of serum samples where blood was drawn from patients with adenocarcinoma and a PSA greater than or equal to 2ng/mL. All men were Caucasian with the exception of 3 who were African American. Non-aggressive prostate cancer was defined as having a Gleason score of 6 (n = 35) and aggressive prostate cancer was characterized as Gleason score 7 and above (n = 69). Biomarker levels were determined using a plate based ELISA for GPC-12 and a bead-based MIA assay for the other markers. Results: By using biostatistical analysis (Simplicity Bio, Switzerland) two models were identified that were able to differentiate between aggressive and non-aggressive prostate cancer. One consisted of a combination of 5 analytes and the other used 6 analytes. Model 1 containing PSA and GPC-1 plus 4 analytes produced a combined sensitivity of 81% and specificity of 78% (AUC 0.81). The second model comprising of GPC-1 with an additional 4 analytes achieved a sensitivity of 72% with a specificity of 76% (AUC 0.76). Both models had a p value of less than 0.05. By itself PSA was a poor predictor of prostate cancer with a sensitivity of 58% and specificity of 43% (AUC 0.55). Conclusions: The analytes identified by the two statistical models demonstrate potential utility for using the combined markers as a new means of differentiating aggressive prostate cancer from non-aggressive cancer. An additional study to further validate these models is currently being constructed.

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Glypican-1 as a Biomarker for Prostate Cancer: Isolation and Characterization

Cited by 44 publications

References 35 publications

Elevated glypican‐1 expression is associated with an unfavorable prognosis in pancreatic ductal adenocarcinoma

Elevated glypican‐1 expression is associated with an unfavorable prognosis in pancreatic ductal adenocarcinoma

Glypican‐3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment

A multivariate index analyte (MIA) assay for differentiating aggressive from nonaggressive prostate cancer.

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