Time-Dependent Changes of Plasma Concentrations of Angiopoietins, Vascular Endothelial Growth Factor, and Soluble Forms of Their Receptors in Nonsmall Cell Lung Cancer Patients Following Surgical Resection

Kopczyńska, Ewa; Dancewicz, Maciej; Kowalewski, Janusz; Makarewicz, Roman; Kardymowicz, Hanna; Kaczmarczyk, Agnieszka; Tyrakowski, Tomasz

doi:10.5402/2012/638352

Cited by 10 publications

(15 citation statements)

References 35 publications

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“…The latest study confirmed that, by regulating the functional connection of lymphatic endothelial cells, Ang2 plays an important role in the occurrence and development of lymph vessels [11]. Clinical studies have found that Ang2 is of great value in the diagnosis, metastasis, and prognosis evaluation of lung cancer and other malignant tumor diseases [5,40,41]. Further intervention studies show that targeted inhibition of Ang2 can inhibit tumor angiogenesis and lymphangiogenesis.…”

Section: Discussionmentioning

confidence: 86%

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The role of microRNA‐93 regulating angiopoietin2 in the formation of malignant pleural effusion

et al. 2017

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The biological roles of miRNAs in the development of malignant pleural effusion (MPE) are unclear. In this study, the miRNA microarray analysis was performed in two different prognosis groups of lung adenocarcinoma patients. Expression profiles of miRNAs in MPEs were identified. With the help of quantification PCR, we confirmed the expression differences of miRNAs and further analyzed their biological functions and relative target genes in vitro. The target gene of miR‐93 was estimated by online database, and also, the protein was tested. The target gene and the binding sites of specific miRNA were estimated by online database. The combining capacity of binding sites was verified by luciferase reporter gene assay, and the target gene protein was tested by western blot. We detected 107 miRNAs with expression differences (n = 10) and confirmed significant expression differences in miR‐93 and miR‐146a in two groups of patients (n = 84). By manipulating miR‐93 expression of human lymphatic endothelial cells (HLEC) and human umbilical vein endothelial cells (HUVEC), we discovered that high expression of miR‐93 inhibited migration, proliferation, and angiogenesis. And also, miR‐93 increased not only apoptosis, but also G1 phase cell block. By using luciferase reporter gene assay and western blot, we confirmed that angiopoietin2 (Ang2) was the target of miR‐93. The data showed that miR‐93 has an inhibiting effect on pleural effusion. By targeting Ang2, miR‐93 regulates angiogenesis and lymphangiogenesis and plays a role in pathogenetic mechanism of MPE. MiR‐93/Ang2 may shed light on potential new targets in cancer treatment.

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Section: Discussionmentioning

confidence: 86%

“…In the treatment of malignant tumor diseases, Ang2 can regulate vascular stability so as to promote the generation of neovascularization. Besides, Ang2 is related to poor prognosis in non‐small‐cell lung cancer . In addition, Ang2 increases significantly in exudative pleural effusion.…”

Section: Discussionmentioning

confidence: 99%

The role of microRNA‐93 regulating angiopoietin2 in the formation of malignant pleural effusion

et al. 2017

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“…Moreover levels of soluble CD105 (s-endoglin), formed by the cleavage of ectodomain of membrane receptors, were higher in patients with various types of cancer compared to normal counterparts, and its levels were also associated to metastases. In NSCLC s-endoglin serum levels were significantly decreased in postoperation patients, confirming its potential use for monitoring and prognosis of lung cancer [59,66]. Progesterone receptor membrane component 1 (Pgrmc1) is a cytochrome b5-related protein induced by carcinogens.…”

Section: Future Perspectives 41 New Potential Lung Cancer Biomarkersmentioning

confidence: 91%

Molecular Biology of Lung Cancer and Future Perspectives for Screening

Tarro¹,

Paolini²,

Rossi³

2019

Mass Spectrometry - Future Perceptions and Applications

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Lung cancer patients have the highest mortality among patients with solid tumors worldwide and their prognosis is strictly stage-associated. However, only 15-20% of patients are diagnosed in stage I, since these early tumors are frequently asymptomatic. Early detection of lung cancer, which allows effective therapeutic intervention, is a promising approach to lowering its mortality rate. However, conventional diagnostic methods for lung cancer, such as chest X-ray and CT of the chest, produce high costs and potentially false-positive results. Thus, the discovery of highly sensitive, specific, noninvasive, and cost-effective lung cancer biomarkers combined with conventional approaches, such as X-rays, may improve the sensitivity of lung cancer screening. Herein, we summarize the most recent studies about the molecular pathology of lung cancer and discuss the advancements expected in the near future, including the potential biomarkers and liquid biopsy approaches for the detection of lung cancer in populations at risk of developing this disease.

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“…[ 2 3 4 ] Indeed, plasma level and wound fluid concentration of proangiogenic factors, such as vascular endothelial growth factors (VEGF) and angiopoietin-2 (Ang2), have been shown to be increased after surgery for a variety of cancers. [ 2 4 5 6 7 8 ] Postoperative plasmas from patients undergoing minimally invasive colorectal resection stimulated endothelial cell migration, invasion, and tube formation in vitro. [9] In murine breast cancer model, primary tumor removal led to upregulation of angiogenesis-associated genes and increase in lung metastatic burden.…”

Section: Introductionmentioning

confidence: 99%

“… [18] Patients with NSCLC have higher plasma Ang2 level, and that is further elevated for at least 30 days after tumor resection. [ 6 7 19 ] The changes after 30 days, especially in the 2nd month, a critical time for starting postoperative adjuvant therapy, [20] however, is unknown. Unknown also is the impact of postoperative plasma Ang2 on angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Plasma angiopoietin-2 is persistently elevated after non-small cell lung cancer surgery and stimulates angiogenesis in vitro

et al. 2016

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Angiopoietin-2 (Ang2) is a key proangiogenic factor, but its role in surgery-induced angiogenesis, a possible cause of cancer recurrence, is still elusive.We measured the plasma Ang2 levels in healthy controls (n = 42) and stage I–IV perioperative nonsmall cell lung cancer (NSCLC) patients (n = 227) with enzyme-linked immunosorbent assay, and examined the impact of Ang2 in the plasmas on in vitro angiogenesis and proliferation of human umbilical vein endothelial cells and human microvascular endothelial cells.Ang2 plasma levels are significantly increased in untreated NSCLC patients (2697 ± 1354 pg/mL) compared to control (1473 ± 560.6 pg/mL) and positively associated with disease stage but not with histology. Ang2 plasma levels in stage I–IIIA NSCLC patients (n = 154) are elevated after the standard open thoracic surgery, following an approximate pattern to increase quickly in the 1st postoperative days (PODs, from preoperative 2342 ± 1084 to POD1: 4485 ± 1617 and POD3: 5370 ± 1879 pg/mL), reach the peak about 2 weeks later (POD14: 6099 ± 2280 pg/mL), drop slowly thereafter (POD28: 3877 ± 1388 and POD42: 3365 ± 1189 pg/mL), and remain significantly higher than preoperative 8 weeks after the procedure (POD56: 2937 ± 943.3 pg/mL). The postoperative plasmas enhance in vitro angiogenesis and Ang2 removal from the plasmas can counteract the effect. The postoperative plasmas stimulate endothelial proliferation independently of Ang2.These results suggest that plasma Ang2 increases after NSCLC surgery and contributes to the proangiogenic property of the postoperative plasmas, thus supporting the possible administration of anti-Ang2 therapy for NSCLC in postoperative adjuvant setting.

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Time-Dependent Changes of Plasma Concentrations of Angiopoietins, Vascular Endothelial Growth Factor, and Soluble Forms of Their Receptors in Nonsmall Cell Lung Cancer Patients Following Surgical Resection

Cited by 10 publications

References 35 publications

The role of microRNA‐93 regulating angiopoietin2 in the formation of malignant pleural effusion

The role of microRNA‐93 regulating angiopoietin2 in the formation of malignant pleural effusion

Molecular Biology of Lung Cancer and Future Perspectives for Screening

Plasma angiopoietin-2 is persistently elevated after non-small cell lung cancer surgery and stimulates angiogenesis in vitro

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