Tie-2, G-CSF, and Leptin as Promising Diagnostic Biomarkers for Endometrial Cancer: A Pilot Study

Roškar, Luka; Klančič, Teja; Knific, Tamara; Rižner, Tea Lanišnik; Smrkolj, Špela

doi:10.3390/jcm10040765

Cited by 7 publications

(21 citation statements)

References 58 publications

(68 reference statements)

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“…AFs’ concentrations in preoperative plasma samples of patients with endometrioid EC (n = 38) and control patients with benign gynecological conditions (e.g., prolapsed uterus or myoma; n = 38) were measured using Luminex xMAP™ multiplexing technology. Our discovery study demonstrated significant differences in the plasma levels of six AFs: sTie-2, G-CSF, and leptin were present in different concentrations in EC versus control patients, and IL-8, neuropilin-1 and follistatin differed among different EC subgroups ( 19 ). The roles of these AFs have been described in detail in our recent review paper ( 12 ).…”

Section: Introductionmentioning

confidence: 80%

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Models including preoperative plasma levels of angiogenic factors, leptin and IL-8 as potential biomarkers of endometrial cancer

et al. 2022

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BackgroundThe diversity of endometrial cancer (EC) dictates the need for precise early diagnosis and pre-operative stratification to select treatment options appropriately. Non-invasive biomarkers invaluably assist clinicians in managing patients in daily clinical practice. Currently, there are no validated diagnostic or prognostic biomarkers for EC that could accurately predict the presence and extent of the disease.MethodsOur study analyzed 202 patients, of whom 91 were diagnosed with EC and 111 were control patients with the benign gynecological disease. Using Luminex xMAP™ multiplexing technology, we measured the pre-operative plasma concentrations of six previously selected angiogenic factors – leptin, IL-8, sTie-2, follistatin, neuropilin-1, and G-CSF. Besides basic statistical methods, we used a machine-learning algorithm to create a robust diagnostic model based on the plasma concentration of tested angiogenic factors.ResultsThe plasma levels of leptin were significantly higher in EC patients than in control patients. Leptin was higher in type 1 EC patients versus control patients, and IL-8 was higher in type 2 EC versus control patients, particularly in poorly differentiated endometrioid EC grade 3. IL-8 plasma levels were significantly higher in EC patients with lymphovascular or myometrial invasion. Among univariate models, the model based on leptin reached the best results on both training and test datasets. A combination of age, IL-8, leptin and G-CSF was determined as the most important feature for the multivariate model, with ROC AUC 0.94 on training and 0.81 on the test dataset. The model utilizing a combination of all six AFs, BMI and age reached a ROC AUC of 0.89 on both the training and test dataset, strongly indicating the capability for predicting the risk of EC even on unseen data.ConclusionAccording to our results, measuring plasma concentrations of angiogenic factors could, provided they are confirmed in a multicentre validation study, represent an important supplementary diagnostic tool for early detection and prognostic characterization of EC, which could guide the decision-making regarding the extent of treatment.

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Section: Introductionmentioning

confidence: 80%

“…Neuropilin-1 plasma level was higher in patients with type 2 EC (G3) compared to patients with lower grade cancer or controls. Follistatin level was higher in patients with LVI, and IL-8 plasma level was higher in patients with metastases ( 19 ). In this validation study, we further evaluated those six AFs on a larger group of patients.…”

Section: Discussionmentioning

confidence: 99%

Models including preoperative plasma levels of angiogenic factors, leptin and IL-8 as potential biomarkers of endometrial cancer

et al. 2022

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“…Elevated sTie2 levels have been associated with certain neoplastic and non-neoplastic diseases and have been explored as circulating biomarkers [ 46 ]. However, in our previous study, we detected significantly lower sTie2 plasma levels in patients with the endometrioid type of EC compared to patients with benign gynecological pathologies [ 5 ].…”

Section: Angiogenic Diagnostic and Therapeutic Biomarkersmentioning

confidence: 90%

“…For larger tumors, EC cells must start to produce angiogenic factors (AFs), i.e., special cytokines, which are secreted into the surrounding tissue and nearby vessels, causing angiogenesis and the delivery of nutrients to the cancerous cells. Elevated AF levels can also be detected in the systemic circulation, indicating a potential non-invasive strategy to detect cancer in its early stages [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and Therapeutic Values of Angiogenic Factors in Endometrial Cancer

Roškar

Rižner

et al. 2021

Biomolecules

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Endometrial cancer (EC) is the most frequent gynecological malignancy in developed countries and requires a relatively invasive diagnostic evaluation and operative therapy as the primary therapeutic approach. Angiogenesis is one of the main processes needed for cancer growth and spread. The production of angiogenic factors (AFs) appears early in the process of carcinogenesis. The detection of AFs in plasma and tissue and a better understanding of the angiogenic properties of EC may contribute not only to earlier but also more specific diagnosis and consequently tailored and individual therapeutic approaches. AFs and their receptors also have high potential as binding sites for targeted cancer therapy. In this review, we discuss angiogenesis in EC and the characteristics of the AFs that most contribute to angiogenesis in EC. We also highlight therapeutic strategies that target angiogenesis as potential EC therapy.

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“…In addition, the procedure is operator dependent, and the different ET cut-offs also affect its clinical utility [6] . Besides TVU, the search for circulating biomarkers to facilitate the early detection of cancer has gained great momentum over the last decade, showing the potential of some blood test techniques at differentiating early stage EC cases from healthy controls, while requiring further verifying [7][8][9][10] . Until now, there are no consensus on protocols for EC screening.…”

Section: Introductionmentioning

confidence: 99%

The application of endometrial sampler SAP-1 to screening of endometrial cancer in postmenopausal women: A diagnostic test study

Yu¹,

Xie²,

Chun-ke³

2021

Int. J. Clin. Obstet. Gynaecol.

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With cytology for screening cervical cancer providing a successful reference, endometrial cancer screening has attracted more attentions recently. The objective of this study is to evaluate the application of endometrial sampler SAP-1 as a screening tool to detect endometrial cancer among postmenopausal women. From August 2018 to February 2021, 54 postmenopausal women were hospitalized for undergoing hysteroscopy examination. Before the procedure, endometrial samples were collected by the method of SAP-1. The histological results were compared with those by hysteroscopy sampling. The satisfactory rate for the endometrial specimen by SAP-1 sampling was 88.9%. The sensitivity, specificity and accuracy rate of SAP-1 sampling for diagnosing the cancer or precancerous lesions of endometrium were 87.5%, 100% and 97.9%, respectively. Among these patients, whether they had bleeding symptoms, endometrial thickening or intrauterine occupying lesions, risk factors for endometrial cancer or not, the diagnostic coincidence rate of SAP-1 sampling was over 96%, and the differences were not statistically significant (P>0.05). In conclusions, in postmenopausal women, SAP-1 sampling is an ideal screening method, regardless of whether the patients have bleeding symptoms, endometrial thickening or intrauterine occupying lesions, endometrial cancer risk factors. The diagnostic coincidence rate is quite high, but it still needs large sample study to verify.

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Tie-2, G-CSF, and Leptin as Promising Diagnostic Biomarkers for Endometrial Cancer: A Pilot Study

Cited by 7 publications

References 58 publications

Models including preoperative plasma levels of angiogenic factors, leptin and IL-8 as potential biomarkers of endometrial cancer

Models including preoperative plasma levels of angiogenic factors, leptin and IL-8 as potential biomarkers of endometrial cancer

Diagnostic and Therapeutic Values of Angiogenic Factors in Endometrial Cancer

The application of endometrial sampler SAP-1 to screening of endometrial cancer in postmenopausal women: A diagnostic test study

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