Relationship between Serum Level of Lymphatic Vessel Endothelial Hyaluronan Receptor-1 and Prognosis in Patients with Lung Cancer

Abstract

Background: Lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) is a hyaluronic acid receptor that is selectively expressed in the endothelia of lymphatic capillaries. The density of lymphatic vessels expressing LYVE-1 on immunohistochemistry negatively correlates with prognosis of patients with non-small-cell lung cancer. However, the relationship between LYVE-1 serum levels and lung cancer staging is unknown.Methods: We collected blood samples from 58 lung cancer patients before treatment and measured LYVE-1 serum levels using an enzyme-linked immunosorbent assay.Results: Mean serum LYVE-1 levels were 1,420 pg/mL. Serum LYVE-1 levels correlated positively with serum albumin levels, but inversely with primary tumor size, leukocyte counts, and platelet counts by Pearson's product-moment correlation coefficient. A high cancer staging, occurrence of lymph-node metastases, and occurrence of distant metastases were significantly associated with low LYVE-1 levels. Moreover, multiple logistic regression analyses revealed that LYVE-1 levels were predictive of the presence of lymph node and distant metastases, independently of the other factors. Kaplan-Meier analysis showed that the survival of patients with serum LYVE-1 ≤1,553 pg/mL was significantly poorer than that of patients with serum LYVE-1 >1,553 pg/mL. This survival difference relative to LYVE-1 levels remained statistically significant after adjusting for age and gender by the Cox proportional-hazard analysis.Conclusion: Serum LYVE-1 is significantly low in lung cancer patients with metastasis, compared with those without. Measuring LYVE-1 levels in lung cancer patients may be useful for evaluating lung cancer progression.

Methylation of RASSF1A and CDH13 Genes in Individualized Chemotherapy for Patients with Non-small Cell Lung Cancer

“…With the influence of various environment, the morbidity and mortality of lung cancer have been growing fast in recent years.Lung cancer threatens people's health and the quality of human life (Nunomiya et al, 2014). Hyper-methylation of promoter region of tumor suppressor genes occurs, so that the gene silencing, and increase the risk of cancer (Shicheng et al, 2014).…”

The optimum marker for the detection of lymphatic vessels

“…Interactions between LYVE-1 and the extracellular matrix glycosaminoglycan, HA, may regulate leukocyte migration through the lymphatic vasculature ( 38 ). The serum level of LYVE-1 has been identified to be significantly lower in patients with lung cancer with metastasis in comparison with those without ( 6 ). It has been suggested that LYVE-1 could be used in predicting cancer progression ( 6 ).…”

“…The serum level of LYVE-1 has been identified to be significantly lower in patients with lung cancer with metastasis in comparison with those without ( 6 ). It has been suggested that LYVE-1 could be used in predicting cancer progression ( 6 ). The interaction between LYVE-1 and HA was identified to be involved in the adhesion of tumor cells to lymphatic vessels ( 39 ).…”

Lymphatic vessel density as a prognostic indicator in Asian NSCLC patients: a meta-analysis

“…However, some studies have claimed that high LVD may be a marker for good prognosis. The study by Nunomiya and colleagues showed that lung cancer patients with lower LYVE-1 levels have poorer prognoses than patients with higher LYVE-1 levels [ 25 ]. Yang and his team demonstrated the role of the epigenetic regulation of desmoplakin in increasing the sensitivity of cancer cells to anticancer drug-induced apoptosis, implying the clinical value of desmoplakin for the treatment of patients with lung cancer [ 45 ].…”

“…Desmoplakin, also known as desmosome-related transmembrane protein, is a desmosomal protein expressed at intercellular junctions. Some studies have shown that lymphatic endothelium markers can be used to predict poor prognoses in NSCLC patients [ 22 – 24 ], but other studies have refuted this view [ 25 – 27 ]. Therefore, whether LVD is a prognostic biomarker for the survival of NSCLC patients remains controversial.…”