Circulating form of human vascular adhesion protein‐1 (VAP‐1): Decreased serum levels in progression of colorectal cancer and predictive marker of lymphatic and hepatic metastasis

Toiyama, Yuji; Miki, Chikao; Inoue, Yasuhiro; Kawamoto, Aya; Kusunoki, Masato

doi:10.1002/jso.21246

Cited by 34 publications

(29 citation statements)

References 37 publications

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“…Although it is uncommon for serum biomarkers to decrease with disease progression, a similar decrease upon development of metastasis was reported in other cancers, for example, vascular adhesion protein-1 (VAP-1) in colorectal cancer. 25 We did not have enough data to compare IFG-I levels in our patients with other serum biomarker levels, but we hope to do so in a larger prospective study, which is currently underway.…”

Section: Discussionmentioning

confidence: 99%

Insulin-Like Growth Factor-1 as a Predictive Biomarker for Metastatic Uveal Melanoma in Humans

Frenkel¹,

Zloto²,

Pe’er³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. High expression levels of insulin-like growth factor-1 (IGF-1) receptor were associated with metastatic uveal melanoma (UM). The purpose of this study was to examine the potential of serum IGF-1 in early detection of liver metastasis.METHODS. IGF-1 serum levels were analyzed using enzymelinked immunosorbent assay for 118 subjects in three different groups: 55 disease-free (DF) UM patients who did not develop metastasis within 10 years of diagnosis; 22 metastatic patients; and 41 healthy subjects. Matched pairs univariate analysis was performed for sera of 19 metastatic patients 12 and 6 months before the diagnosis of metastasis and on the day of diagnosis, both as time groups and normalized levels per patient. IGF-1 levels were compared among groups by analysis of variance and Student t-test. RESULTS.Mean 6 SD IGF-1 serum levels for the control, DF, and metastatic groups were 152.48 6 49.76, 119.92 6 60.66, and 96.99 6 56.91 ng/mL, respectively (P < 0.001). Normalized changes in IGF-1 per metastatic patient from 6 months prior to the diagnosis of metastases compared to the day of diagnosis of metastases showed a decreasing trend.CONCLUSIONS. IGF-1 levels in 10-years' disease-free UM patients were significantly lower than those in healthy subjects and were even lower in metastatic patients. IGF-1 levels decreased toward the diagnosis of metastases. Therefore, serum IGF-1 level may be used as a predictive biomarker for metastatic UM when measured repeatedly. (Invest Ophthalmol Vis Sci. 2013; 54:490-493) DOI:10.1167/iovs.12-10228 U veal melanoma (UM) is the most common primary intraocular malignant tumor in adults, 1 albeit a rare tumor with a mean age-adjusted incidence in the United States of 5.1 per million, representing only 3.1% of all recorded cases of melanoma.2 The liver is the predominant metastatic organ, and in the collaborative ocular melanoma study (COMS), the liver was involved in 89% of cases. 3Brachytherapy and external irradiation (proton beam, stereotactic radiosurgery, or gamma knife) are the most common treatment options for small-to medium-sized tumors, with a success rate of approximately 90%, while enucleation remains the common treatment for large tumors. Despite the high success rate in treating the primary tumors, the 5-and 10-year cumulative rates for developing metastases are 25% and 34%, respectively, with 80% of the metastatic patients dying within 1 year and 92% within 2 years of the diagnosis of metastases. 4 However, metastases have been diagnosed even more than 40 years from enucleation.5 These findings led to the hypothesis that micrometastases had already been seeded at the time of diagnosis and developed over time as a result of unknown factors until metastatic disease was diagnosed. 6 Currently there is no adjuvant chemotherapy to eliminate micrometastases, and treatments for overt metastatic disease are of limited value except for a subgroup of patients who are diagnosed early enough to allow complete surgical resection of liver metastases. 7,8 Liver resection may inc...

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Section: Discussionmentioning

confidence: 99%

Insulin-Like Growth Factor-1 as a Predictive Biomarker for Metastatic Uveal Melanoma in Humans

Frenkel¹,

Zloto²,

Pe’er³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…Moreover, a soluble form of VAP-1 in serum may serve as a predictive marker in cancer because increased soluble VAP-1 levels were found in colorectal patients, and soluble VAP-1 proved to be an independent marker for predicting metastatic disease (44). Thus, the membrane-bound VAP-1 may serve as a recruitment molecule for myeloid cells on tumor endothelium, whereas the soluble VAP-1-the cellular origin, mechanism of formation, and functions of which remain to be elucidated-may be a surrogate marker of beneficial tumor-induced inflammation.…”

Section: Cd11bmentioning

confidence: 99%

Vascular Adhesion Protein-1 Enhances Tumor Growth by Supporting Recruitment of Gr-1+CD11b+ Myeloid Cells into Tumors

et al. 2009

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Cancer growth is regulated by several nonmalignant cell types, such as leukocytes and endothelial cells, which reside in the stroma of the tumor. Vascular adhesion protein-1 (VAP-1) is an amine oxidase enzyme that is expressed on the surface of endothelial cells. It supports leukocyte traffic into inflamed tissues, but nothing is known about its possible role in cancer biology in vivo. Here, we report that B16 melanoma and EL-4 lymphoma remain smaller in VAP-1-deficient mice than in wild-type controls. We found an unexpected defect in tumor angiogenesis in the absence of VAP-1. VAP-1 also selectively enhanced the recruitment of Gr-1 + CD11b + myeloid cells into the tumors. Generation of mice expressing enzymatically inactive VAP-1 showed that the oxidase activity of VAP-1 was necessary to support neoangiogenesis, myeloid cell recruitment, and tumor growth in vivo. These data describe VAP-1 as the first adhesion molecule known to be involved in the recruitment of Gr-1 + CD11b + myeloid cells into tumors. They also suggest that VAP-1 is a potential new tool for immunotherapy of tumors that could be exploited to reduce tumor burden by controlling the traffic of Gr-1 + CD11b + myeloid cells.

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“…Increased serum VAP-1 levels in chronic liver disease and multiple sclerosis compared to healthy individuals have been reported previously [6,7]. In addition, low serum VAP-1 is associated with disease relapse and worse prognosis in colon cancer and gastric cancer [8,9]. However, there is insufficient information about the correlation of serum VAP-1 level and the prognosis of gastric cancer patients at different stages of the disease.…”

Section: Introductionmentioning

confidence: 97%

Relationship between Serum Soluble Vascular Adhesion Protein-1 Level and Gastric Cancer Prognosis

Kaplan

Küçüköner²,

İnal³

et al. 2014

Oncol Res Treat

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Background: Vascular adhesion protein-1 (VAP-1) is a glycoprotein that mediates tissue-selective lymphocyte adhesion in a sialic acid-dependent manner. The prognostic importance of VAP-1 was determined in various human cancers. The aim of this study was to determine the relationship between VAP-1 and prognosis of gastric cancer. Materials and Methods: Serum of operable and metastatic gastric cancer patients was collected before treatment (surgery, radiotherapy, and/or chemotherapy). VAP-1 levels were measured by enzyme-linked immunosorbent assay. Results: A total of 86 gastric cancer patients (32 female, 54 male) were included in the study. Curative surgical treatment was performed in 54 (62.8%) patients. The mean serum VAP-1 level was 324.4 pg/ml and significantly higher in operable gastric cancer patients compared to metastatic gastric cancer patients (383.1 ± 173.5 vs. 225.2 ± 113.9 pg/ml; p < 0.001). When a cut-off value for VAP-1 of 218.8 pg/ml was determined by receiver operating characteristic (ROC) curves for presence of metastasis, sensitivity and specificity were 81.5 and 65.6%, respectively. Patients with decreased VAP-1 levels had a significantly poorer prognosis compared to patients with increased serum VAP-1 levels (median survival 8.2 vs. 23.5 months; p < 0.001). Multivariate analysis showed that VAP-1 is an independent prognostic factor of gastric cancer (odds ratio 2.3, 95% confidence interval 1.1-4.9; p = 0.032). Conclusion: A low serum VAP-1 level may be an indicator of poor prognosis in gastric cancer. This study demonstrated that low serum VAP-1 levels are associated with poor prognosis in gastric cancer patients.

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Circulating form of human vascular adhesion protein‐1 (VAP‐1): Decreased serum levels in progression of colorectal cancer and predictive marker of lymphatic and hepatic metastasis

Abstract: Preoperative low sVAP-1 level is associated with poor prognosis in colorectal cancer. Measuring serum sVAP-1 may provide valuable information in predicting patients with lymph node or hepatic metastasis.

Cited by 34 publications

References 37 publications

Insulin-Like Growth Factor-1 as a Predictive Biomarker for Metastatic Uveal Melanoma in Humans

Insulin-Like Growth Factor-1 as a Predictive Biomarker for Metastatic Uveal Melanoma in Humans

Vascular Adhesion Protein-1 Enhances Tumor Growth by Supporting Recruitment of Gr-1+CD11b+ Myeloid Cells into Tumors

Relationship between Serum Soluble Vascular Adhesion Protein-1 Level and Gastric Cancer Prognosis

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