scholarly journals MiR-574-5p: A Circulating Marker of Thoracic Aortic Aneurysm

2019 ◽  
Vol 20 (16) ◽  
pp. 3924 ◽  
Author(s):  
Boileau ◽  
Cardenas ◽  
Courtois ◽  
Zhang ◽  
Rodosthenous ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Extracellular Vesicles ◽  
Thoracic Aortic Aneurysm ◽  
Characteristic Curve ◽  
Serum Levels ◽  
Aortic Tissue ◽  
Wild Type ◽  
Serum Samples ◽  
Tissue Samples ◽  
Aortic Media

Thoracic aortic aneurysm (TAA) can lead to fatal complications such as aortic dissection. Since aneurysm dimension poorly predicts dissection risk, microRNAs (miRNAs) may be useful to diagnose or risk stratify TAA patients. We aim to identify miRNAs associated with TAA pathogenesis and that are possibly able to improve TAA diagnosis. MiRNA microarray experiments of aortic media tissue samples from 19 TAA patients and 19 controls allowed identifying 232 differentially expressed miRNAs. Using interaction networks between these miRNAs and 690 genes associated with TAA, we identified miR-574-5p as a potential contributor of TAA pathogenesis. Interestingly, miR-574-5p was significantly down-regulated in the TAA tissue compared to the controls, but was up-regulated in serum samples from a separate group of 28 TAA patients compared to 20 controls (p < 0.001). MiR-574-5p serum levels discriminated TAA patients from controls with an area under the receiver operating characteristic curve of 0.87. In the Fbn1C1041G/+ mouse model, miR-574-5p was down-regulated in aortic tissue compared to wild-type (p < 0.05), and up-regulated in plasma extracellular vesicles from Fbn1C1041G/+ mice compared to wild-type mice (p < 0.05). Furthermore, in vascular smooth muscle cells, angiotensin II appears to induce miR-574-5p secretion in extracellular vesicles. In conclusion, miR-574-5p is associated with TAA pathogenesis and may help in diagnosing this disease.

scholarly journals Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 154 ◽  
Author(s):  
Gianluca L. Perrucci ◽  
Erica Rurali ◽  
Maria Corlianò ◽  
Maria Balzo ◽  
Michela Piccoli ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Marfan Syndrome ◽  
Thoracic Aortic Aneurysm ◽  
Cyclophilin A ◽  
Aortic Tissue ◽  
Tissue Samples ◽  
Abdominal Aortic ◽  
Tgf Β1 ◽  
In Vitro Treatment

Background: Marfan syndrome (MFS) is a genetic disease, characterized by thoracic aortic aneurysm (TAA), which treatment is to date purely surgical. Understanding of novel molecular targets is mandatory to unveil effective pharmacological approaches. Cyclophilin A (CyPA) and its receptor EMMPRIN are associated with several cardiovascular diseases, including abdominal aortic aneurysm. Here, we envisioned the contribution of CyPA/EMMPRIN axis in MFS-related TAA. Methods: We obtained thoracic aortic samples from healthy controls (HC) and MFS patients’ aortas and then isolated vascular smooth muscle cells (VSMC) from the aortic wall. Results: our findings revealed that MFS aortic tissue samples isolated from the dilated zone of aorta showed higher expression levels of EMMPRIN vs. MFS non-dilated aorta and HC. Interestingly, angiotensin II significantly stimulated CyPA secretion in MFS-derived VSMC (MFS-VSMC). CyPA treatment on MFS-VSMC led to increased levels of EMMPRIN and other MFS-associated pro-fibrotic mediators, such as TGF-β1 and collagen I. These molecules were downregulated by in vitro treatment with CyPA inhibitor MM284. Our results suggest that CyPA/EMMPRIN axis is involved in MFS-related TAA development, since EMMPRIN is upregulated in the dilated zone of MFS patients’ TAA and the inhibition of its ligand, CyPA, downregulated EMMPRIN and MFS-related markers in MFS-VSMC. Conclusions: these insights suggest both a novel detrimental role for CyPA/EMMPRIN axis and its inhibition as a potential therapeutic strategy for MFS-related TAA treatment.

scholarly journals Detection of Pathological Changes in the Aorta during Thoracic Aortic Aneurysm Progression on Molecular Level

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Miroslava Rabajdová ◽  
Peter Urban ◽  
Ivana Špaková ◽  
Artemiou Panagiotis ◽  
Michaela Ferenčáková ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Aortic Aneurysm ◽  
Thoracic Aortic Aneurysm ◽  
Aortic Wall ◽  
Pathological Process ◽  
Aortic Tissue ◽  
Mrna Levels ◽  
Tissue Samples ◽  
Extracellular Matrix Components

The progression of thoracic aortic aneurysm depends on regulation of aortic wall homeostasis and on changes in the structural components of the extracellular matrix, which are affected by multiple molecular signalling pathways. We decided to correlate the diameter of ascending thoracic aneurysm with gene expression of inflammation markers (IL-6, CRP), cytokine receptors (IL-6R, TNFR1, and TNFR2), and extracellular matrix components (Emilin-1, MMP9, and TIMP) for detection of the degree of pathological process of TAA formation. The experimental group was divided into three groups according to the diameter of the aortic aneurysm. Whole blood and tissue samples were properly collected and used for nucleic acid, chromatin, and protein isolation. The mRNA levels were detected by qRT-PCR. For the detection of protein levels a Cytokine Array IV assay kit was used in combination with a biochip analyzer. In aortic tissue, significant positive correlations were found between increased mRNA levels of inflammatory cytokines (CRP and IL-6) on both mRNA levels in tissue and protein from the blood with maximum in stage 3. Changes of gene expression of selected genes can be used for the experimental study of the inflammatory receptor inhibitors during trials targeted on slowing down the progress of aortic wall aneurysm.

scholarly journals Long Noncoding RNAs CARMN, LUCAT1, SMILR, and MALAT1 in Thoracic Aortic Aneurysm: Validation of Biomarkers in Clinical Samples

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Vaiva Patamsytė ◽  
Giedrius Žukovas ◽  
Dovydas Gečys ◽  
Diana Žaliaduonytė ◽  
Povilas Jakuška ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Blood Plasma ◽  
Thoracic Aortic Aneurysm ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Clinical Samples ◽  
Aortic Tissue ◽  
Relative Expression ◽  
Clinical Patient ◽  
Diagnostic Potential

Background and Objectives. Thoracic aortic aneurysm (TAA) is a silent disease characterised by aortic wall expansion and vascular smooth muscle cell (VSMC) dedifferentiation from contractile to synthetic phenotype. Long noncoding RNAs (lncRNAs) involved in VSMC phenotypic regulation could be considered as potential diagnostic indicators and therapeutic targets of TAA. In vitro studies show that lncRNAs CARMN, LUCAT1, MALAT1, and SMILR are associated with the VSMC phenotypic state. Our aim was to test if these lncRNAs are dysregulated during TAA formation in clinical patient samples. Materials and Methods. Relative expression of lncRNAs CARMN, LUCAT1, SMILR, and MALAT1 was tested in clinical aortic tissue and blood plasma samples from TAA and non-TAA patients using the qRT-PCR method. The Mann–Whitney U test was used to compare ΔCt values between the study groups. ROC curve analysis was performed to evaluate the diagnostic value of plasma lncRNAs. Results. We found significantly reduced CARMN (p=0.033) and LUCAT1 (p=0.009) expression in aortic tissue samples from TAA patients. Relative expression of MALAT1 (p=0.117) and SMILR (p=0.610) did not differ in aortic tissue between the TAA and non-TAA groups. Expression of both LUCAT1 and SMILR was significantly decreased in TAA patients’ blood plasma compared to controls (p=0.018 and p=0.032, respectively). However, only LUCAT1 showed the ability to discriminate aneurysmal disease in patients’ blood plasma (AUC=0.654, 95%CI=0.534‐0.775, p=0.018). Conclusions. We have shown that the expression of lncRNAs CARMN and LUCAT1 is reduced in dilated aortic tissue and that the LUCAT1 and SMILR expression is lower in the blood plasma of TAA patients. Decreased LUCAT1 expression in TAA patients’ blood plasma may have diagnostic potential in discriminating patients with TAA.

scholarly journals Different expression pattern of human cytomegalovirus-encoded microRNAs in circulation from virus latency to reactivation

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Wanqing Zhou ◽  
Cheng Wang ◽  
Meng Ding ◽  
Yuying Bian ◽  
Yujie Zhong ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Characteristic Curve ◽  
Antiviral Treatment ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Prediction Ability ◽  
Stem Loop ◽  
Virus Latency ◽  
Polymerase Chain

Abstract Background Human cytomegalovirus (HCMV) is a beta-hersvirinae that has a high latent infection rate worldwide and can cause serious consequences in immunocompromised patients when reactivation; however, the mechanism of how HCMV convert from latent to reactivation has rarely been investigated. In the present study, we aimed to perform a comprehensive analysis of the HCMV-encoded microRNA (miRNA) profile in serum of patients upon HCMV reactivation from latency and to further evaluate its clinical significance for the disease monitoring and preventing usefulness. Methods Serum samples from 59 viremia patients and 60 age-gender matched controls were enrolled in this study for screening and validation of different expression of HCMV miRNAs. Serum concentrations of 22 known HCMV miRNAs were determined by a hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay. HCMV DNA was measured by quantitative real-time PCR (qPCR) with the whole blood sample. Serum HCMV IgG and IgM were assessed using enzyme linked immunosorbent assay (ELISA). Another 47 samples from 5 patients at different time points were collected to evaluate the monitoring effectiveness and disease prediction ability of differential expression HCMV-miRNAs during the antiviral treatment. Results The RT-qPCR analysis revealed that the serum levels of 16 of the 22 examined HCMV miRNAs were elevated in HCMV viremia patients compared with controls, and a profile of 8 HCMV miRNAs including hcmv-miR-US25-2-3p, hcmv-miR-US4-5p, hcmv-miR-US25-2-5p, hcmv-miR-US25-1-3p, hcmv-miR-US25-1, hcmv-miR-UL36, hcmv-miR-UL148D, hcmv-miR-US29-3p were markedly elevated (fold change > 2, P < 0.01). Receiver operating characteristic curve (ROC) analysis were performed on the selected HCMV-miRNAs in all of the patients and controls that enrolled in this study, and which ranged from 0.72 to 0.80 in the autoimmune patients. In addition, hcmv-miR-US25-1-3p levels were significantly correlated with HCMV DNA load (r = 0.349, P = 0.007), and were obviously higher in the reactivation set than the latency set in the autoimmune patients, which could be a predictor for the monitoring of the antiviral treatment. Conclusions HCMV miRNAs profile showed markedly shift-switch from latency to reactivation in circulation from HCMV infected patients and hcmv-miR-US25-1-3p may be served as a predictor for the switch upon reactivation from latency in patients suffered with autoimmune diseases.

Exploring serum metabolic markers for the discrimination of ccRCC from renal angiomyolipoma by metabolomics

2020 ◽  
Vol 14 (8) ◽  
pp. 675-682
Author(s):  
Mingfeng Xiang ◽  
Feng Du ◽  
Jing Dai ◽  
Ling Chen ◽  
Ruijin Geng ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Uric Acid ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Resonance Spectroscopy ◽  
Renal Angiomyolipoma ◽  
Serum Samples ◽  
Metabolic Markers ◽  
Cell Renal Carcinoma

Aim: The discrimination of renal cell carcinoma from renal angiomyolipoma (RAML) is crucial for the effective treatment of each. Materials & methods: Serum samples were analyzed by nuclear magnetic resonance spectroscopy-based metabolomics and a number of metabolites were further quantified by HPLC–UV. Results: Clear-cell renal carcinoma (ccRCC) was characterized by drastic disruptions in energy, amino acids, creatinine and uric acid metabolic pathways. A logistic model for the differential diagnosis of RAML from ccRCC was established using the combination of serum levels of uric acid, the ratio of uric acid to hypoxanthine and the ratio of hypoxanthine to creatinine as variables with area under the curve of the receiver operating characteristic curve value of 0.907. Conclusion: Alterations in serum purine metabolites may be used as potential metabolic markers for the differential diagnosis of ccRCC and RAML.

Abstract 4280: Combination of Doxycycline and Losartan is an Effective Secondary Prevention Treatment for the Thoracic Aortic Aneurysm in Marfan Syndrome

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hh C Yang ◽  
Cornelis van Breemen ◽  
Ada Chung
Keyword(s):  
Aortic Aneurysm ◽  
Secondary Prevention ◽  
Marfan Syndrome ◽  
Thoracic Aortic Aneurysm ◽  
Combined Treatment ◽  
Elastic Fiber ◽  
Specific Inhibitor ◽  
Untreated Group ◽  
Vasomotor Function ◽  
Aortic Media

Losartan, an antihypertensive drug, has been shown to prevent thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) through the inhibition of transforming growth factor (TGF)-β. Recently we have suggested doxycycline, a non-specific inhibitor of matrix metalloproteinases (MMPs), suppressed aneurysm and normalized vasomotor function in TA. We hypothesized that a combination of doxycycline and losartan could be effective in the secondary prevention to ameliorate TAA in MFS. A well-defined mouse model of Marfan syndrome (Fbn1 C1039G/+ ) were untreated (n=20), given doxycycline (0.24g/L, n=15), losartan (0.6g/L, n=15), or doxycycline+losartan (0.12g/L+0.3g/L, respectively, n=15) from drinking water at the age of 4 months. The littermate Fbn1 +/+ mice served as control (n=20). Ascending thoracic aortae from each group at 9 months were studied. Mortality (2%) and TAA (increase in diameter by >35%) were observed in the untreated group. Mild aneurysm (diameter of aorta was increased by 15% compared with controls) was evident in either losartan-or doxycycline-groups, but TAA was prevented by the combined treatment. From the aortic media of untreated, losartan- and doxcycline-groups, elastic fiber degeneration shown on Movat’s histology was pronounced, which accompanied with increased aortic stiffness. Combined treatment attenuated elastic fiber degradation and normalized the aortic elasticity to the control levels. The impairment of smooth muscle contraction and endothelial-dependent relaxation in the untreated group were also completely normalized by the combined treatment. Either losartan- or doxcycline-groups improved aortic contractility by 75% compared with the untreated, but was not effective in improving endothelium-dependent relaxation. Combined treatment reduced activities of MMP-2 and -9 in the aortic media by 60 – 80%, and activation of TGF-β by 70%. Delayed treatment reduced effectiveness of both losartan and doxycycline in the prevention of TAA. Combination of doxycycline and losartan is effective in the secondary prevention to preserve elastic fiber integrity and normalize vasomotor function, indicating that both MMP and TGF-β are crucial mediators in TAA formation in MFS.

scholarly journals piRNA-823 Is a Unique Potential Diagnostic Non-Invasive Biomarker in Colorectal Cancer Patients

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 598
Author(s):  
Norhan A. Sabbah ◽  
Wael M. Abdalla ◽  
Walid A. Mawla ◽  
Nagla AbdAlMonem ◽  
Amal F. Gharib ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Serum Levels ◽  
P Element ◽  
Serum Samples ◽  
Expression Levels ◽  
Non Invasive ◽  
Colorectal Cancer Patients

Early detection of colorectal cancer (CRC) is the most important factor in deciding its prognosis, so the need to develop an accurate screening test is a must. P-element induced wimpy testis (PIWI) RNA-823 (piR-823) is one of the first piRNAs recognized to be linked to malignancy. We aimed to investigate the expression levels of piR-823 in both serum and tissues of colorectal cancer patients and the ability to use its serum level as a non-invasive diagnostic biomarker to detect colorectal cancer. We determined piR-823 expression levels in 84 serum samples of CRC patients, 75 serum samples of healthy controls, and biological specimens obtained from the 84 patients with colorectal cancer from both the tumor tissues and the normal neighboring tissues using quantitative real-time reverse transcriptase-PCR. We showed that piR-823 had significantly higher serum and tissue expression levels in CRC patients compared to the controls. We observed a significant positive correlation between piR-823 serum levels and the staging of CRC, with significantly higher levels exhibiting advanced stages of CRC (III and IV). This translates into poorer differentiation and lymph node metastasis. The receiver operating characteristic curve (ROC curve) test showed 83.3% sensitivity and 89.3% specificity at a cut-off value of >5.98-fold change, with an area under the curve of 0.933 (p < 0.0001) concerning the ability of piR-823 in diagnosing patients with colorectal carcinoma. piR-823 expression is upregulated in colorectal cancer patients’ serum and tissues, and it can be used as a diagnostic noninvasive biomarker for CRC.

scholarly journals Assessment of Computational Histopathology in Thoracic Aortic Aneurysm

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Michael DeBrota ◽  
Muhammad Idrees ◽  
Benjamin Landis
Keyword(s):  
Aortic Aneurysm ◽  
Thoracic Aortic Aneurysm ◽  
Elastic Fiber ◽  
Aortic Tissue ◽  
Strongly Correlated ◽  
Medial Degeneration ◽  
Aortic Replacement ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Cellular Area

Background and Hypothesis: Thoracic aortic aneurysm (TAA) histopathology includes elastic fiber (EF) abnormalities, mucoid extracellular matrix (MECM) accumulation, and smooth muscle derangement in the aortic medial layer. While semi-quantitative grading of these characteristics is a standard practice, computational characterization of medial layer components may facilitate novel quantitative analyses at higher throughput. We hypothesized that computational results would correlate with results of semi-quantitative grading of aortic histopathology. Experimental Design: Formalin-fixed, paraffin-embedded human aortic tissue sections were stained with Movat’s pentachrome to characterize aortic microstructure. Sections were also immunostained for nitrotyrosine residues to assess oxidative stress. Samples were initially graded semi-quantitatively by two independent blinded readers. Next, computational histopathology software was used a) to quantify the proportions of EF, MECM, and cellular area in the medial layer of pentachrome-stained sections and b) to quantify the distribution and intensity of positive nitrotyrosine staining in immunostained sections. Association between semi-quantitative grading and computed values was tested with ANOVA. Results: The cohort included 74 participants who underwent prophylactic aortic replacement for TAA and 23 healthy controls. The mean age was 54±17 years. On average, EFs accounted for 49% (range 6-90%) of medial tissue area, whereas MECM accounted for 25% (1-73%). The overall semi-quantitative grade of medial degeneration severity was associated with decrease in EF fraction (p=0.02). The grade of EF thinning also strongly correlated with decrease in EF fraction (p=1x10-6). Meanwhile, grade for accumulation of MECM was associated with increase in MECM (p=0.004). Increased semi-quantitative grading for nitrotyrosine levels was associated with increased nuclear signal optical density (p=9x10-10) and greater percentage of cells labeled as strongly positive (p=8x10-10). Conclusion and Potential Impact: We observed significant correlations between computed quantitative values and semi-quantitative grading. This suggests that computational histopathology is a valid method for investigation of human TAA tissues.

Abstract 307: Circulating sRAGE is Associated With Aortic Dysfunction in Mice Models of Thoracic Aortic Aneurysm

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Josephine Galatioto ◽  
Eric Lai ◽  
Maria Bintanel-Morcillo ◽  
Tao Wang ◽  
Giovanni Ferrari ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Mouse Models ◽  
Vascular Remodeling ◽  
Thoracic Aortic Aneurysm ◽  
Aortic Disease ◽  
Aortic Dilatation ◽  
Wild Type ◽  
Aneurysm Formation ◽  
Elastin Degradation ◽  
Medial Thickening

Backgound: The Receptor for Advanced Glycation End products (RAGE) and its ligands are associated with vascular remodeling and trigger the release of a soluble receptor (sRAGE). We demonstrated that sRAGE is elevated in patients with thoracic aortic disease such as patients with bicuspid aortic valve and Marfan syndromes. Circulating sRAGE in these patients correlates with the presence of a dysfunctional aortic structure without linearly correlating with increasing aortic diameter. We hypothesized that elevated sRAGE levels are the result of structural degeneration during aortic aneurysm formation and that they are affected by pharmacological treatments aimed to inhibit vascular remodeling. Methods: Circulating sRAGE was tested by ELISA in two mouse models of thoracic aortic aneurysm (TAA): the AngII chronic infusion model and the hypomorphic FBN1 mgR/mgR . C57BL6 mice were treated with AngII via osmotic pump for 28 days with or without losartan in drinking water. FBN1 mgR/mgR mice were treated with losartan starting from postnatal day 16 (p16). Ascending aorta and blood were collected at day 28 of AngII infusion or at p60 in the hypomorphic model. Aortic dilatation and degeneration were tested by echocardiography and histological analysis. Results: Plasma sRAGE is significantly higher in AngII treated animals when compared to controls (118.1± 8.3 vs 45.6±5.01 pg/ml, p <0.0001) and is associated with aortic aneurysm formation and increased medial thickening. Similarly, sRAGE levels are higher in FBN1 mgR/mgR mice compared to age-matched wild type (1939 ± 320.5 vs 45.6±5.01 pg/ml, p <0.0001) in concomitance with elastin degradation (media score 3.5± 0.8 vs 1.03.5± 0.2, p <0.05) and proximal aorta enlargement. Plasma sRAGE decreases in AngII and FBN1 mgR/mgR mice treated with losartan when compared to age matched untreated or wild type mice (73±24.5 vs 118.1 ± 8.296 pg/ml, p<0.05 and 260.7 ± 4.333 vs 1939 ± 320.5 pg/ml, p<0.001) together with reduced aorta dilatation, medial thickening and elastin fragmentation. Conclusion: sRAGE is elevated in the presence of aortic dilatation in mouse models of TAA, as seen in human aneurysmal patients. These results suggest that sRAGE may be used as a circulating biomarker to assess disease severity in patients with TAA.

Chemokine receptor CXCR4: What is its role in gastrointestinal cancer?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14687-e14687
Author(s):  
Lucia Lombardi
Keyword(s):  
Prognostic Factor ◽  
Gastrointestinal Cancer ◽  
Normal Tissue ◽  
Serum Levels ◽  
Tumor Stage ◽  
Response To Therapy ◽  
Serum Samples ◽  
Tissue Samples ◽  
Before And After ◽  
Advanced Stages

e14687 Background: Multiple metastasis is the predominant cause of colorectal cancer (CC) and pancreatic cancer (PC) related mortality. Chemokines receptors have been implicated in cancer metastatic process by directing the migration of tumour cells to sites of metastasis. However, their clinical relevance in gastrointestinal cancer has not been defined. The aim of our study was to evaluate the possible role of CXCR4 as prognostic factor in CC and PC. Methods: Quantitative determination of CXCR4 in serum samples were collected before and after surgery from 36 CC and 23 PC patients later treated with adjuvant (Ad) therapy or for metastatic (Meta) disease (19 Ad-and 17 Meta-CC; 15Ad-PC and 8 Meta-PC) and from 31 healthy controls (HC) enrolled as controls group, was performed by means of ELISA. Relative expression levels of CXCR4 in matched-pairs of tumour and adjacent normal tissue samples collected from the same 36 CC and 15 Ad-PC patients, were determined by means of qRT-PCR using the QuantiFast SYBR Green PCR kit. Results: Compared to HC, pre-operative CXCR4 serum levels were increased in both CC and PC patients. Post-operative serum levels were higher than those observed pre-operatively in 42% and 47% of patients with Ad- and Meta-CC, respectively. Conversely, in 53% and 50% of patients with Ad- and Meta-PC, CXCR4 serum levels decreased after surgical treatment. Furthermore, higher levels of CXCR4 were associated with advanced stages and in PC with lymph nodes involvement. In addition, CXCR4 was over-expressed in tumor compared to normal tissue in 42% and 41% of patients with Ad- and Meta-CC, and in 73% of patients with Ad-PC. In relation to clinical phenotype, all these patients had stage T3N1 disease in both disease. Conclusions: Our data showed that CXCR4 levels may be associated with tumor stage and disease progression in CC and PC patients. Further studies with larger samples size, might confirm the role for CXCR4 as prognostic factor and/or marker of patients’ response to therapy.

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