Plasma Levels of Matrix Metalloprotease MMP-9 and Tissue Inhibitor TIMP-1 in Caucasian Patients with Polypoidal Choroidal Vasculopathy

Sørensen, Jakob Ørskov; Subhi, Yousif; Molbech, Christopher Rue; Nielsen, Marie Krogh; Sørensen, Torben Lykke

doi:10.3390/vision4020027

Cited by 3 publications

(3 citation statements)

References 33 publications

(53 reference statements)

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“…Levels of the biomarker TIMP-1 has previously been described as dependent on age in some studies [11,12], but to our knowledge, the possible age dependency has not been evaluated in a large cohort study.…”

Section: Introductionmentioning

confidence: 87%

Serological cancer-associated protein biomarker levels at bowel endoscopy: Increased risk of subsequent primary malignancy

Piper

Nielsen

Christensen

2022

TUB

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BACKGROUND: It was previously shown in three subpopulations that subjects not identified with colorectal cancer (CRC) at bowel endoscopy, but with increased serological cancer-associated protein biomarker levels had an increased risk of being diagnosed with subsequent malignant diseases. Objective: The aim of the present study was to perform a pooled analysis of subjects from the three subpopulations and subsequently validate the results in an independent study. The study population denoted the training set includes N = 4,076 subjects with symptoms attributable to CRC and the independent validation set N = 3,774 similar subjects. METHODS: Levels of CEA, CA19-9, TIMP-1 and YKL-40 were determined in blood samples collected prior to diagnostic bowel endoscopy. Follow-up of subjects not diagnosed with CRC at endoscopy, was ten years and identified subjects diagnosed with primary intra- or extra-colonic malignant diseases. The primary analysis was time to a newly diagnosed malignant disease and was analyzed with death as a competing risk in the training set. Subjects with HNPCC or FAP were excluded. The cumulated incidence was estimated for each biomarker and in a multivariate model. The resulting model was then validated on the second study population. RESULTS: In the training set primary malignancies were identified in 515 (12.6%) of the 4,076 subjects, who had a colorectal endoscopy with non-malignant findings. In detail, 33 subjects were subsequently diagnosed with CRC and 482 subjects with various extra-colonic cancers. Multivariate additive analysis of the dichotomized biomarkers demonstrated that CEA (HR = 1.50, 95% CI:1.21–1.86, p < 0.001), CA19-9 (HR = 1.41, 95% CI:1.10–1.81, p = 0.007) and TIMP-1 (HR = 1.25 95% CI: 1.01–1.54, p = 0.041) were significant predictors of subsequent malignancy. The cumulated incidence at 5 years landmark time was 17% for those subjects with elevated CEA, CA19-9 and TIMP-1 versus 6.7% for those with low levels of all. When the model was applied to the validation set the cumulated 5-year incidence was 10.5% for subjects with elevated CEA, CA19-9 and TIMP-1 and 5.6% for subjects with low levels of all biomarkers. Further analysis demonstrated a significant interaction between TIMP-1 and age in the training set. The age dependency of TIMP-1 indicated a greater risk of malignancy in younger subjects if the biomarker was elevated. This observation was validated in the second set. CONCLUSION: Elevated cancer-associated protein biomarker levels in subjects with non-malignant findings at large bowel endoscopy identifies subjects at increased risk of being diagnosed with subsequent primary malignancy. CEA, CA19-9 and TIMP-1 were significant predictors of malignant disease in this analysis. TIMP-1 was found dependent on age. The results were validated in an independent symptomatic population.

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Section: Introductionmentioning

confidence: 87%

Serological cancer-associated protein biomarker levels at bowel endoscopy: Increased risk of subsequent primary malignancy

Piper

Nielsen

Christensen

2022

TUB

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“…MMP9, which is involved in extracellular matrix metabolism, was found to be associated with Asian patients with PCV. Another study reported that MMP9 was not found in White patients with PCV 37…”

Section: Updates On Risk Factors and Biomarkers For Pcv Developmentmentioning

confidence: 97%

Polypoidal Choroidal Vasculopathy: Updates on Risk Factors, Diagnosis, and Treatments

Ruamviboonsuk

Cheung

Chainakul

et al. 2023

Asia-Pacific Journal of Ophthalmology

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There have been recent advances in basic research and clinical studies in polypoidal choroidal vasculopathy (PCV). A recent, large-scale, population-based study found systemic factors, such as male gender and smoking, were associated with PCV, and a recent systematic review reported plasma C-reactive protein, a systemic biomarker, was associated with PCV. Growing evidence points to an association between pachydrusen, recently proposed extracellular deposits associated with the thick choroid, and the risk of development of PCV. Many recent studies on diagnosis of PCV have focused on applying criteria from noninvasive multimodal retinal imaging without requirement of indocyanine green angiography. There have been attempts to develop deep learning models, a recent subset of artificial intelligence, for detecting PCV from different types of retinal imaging modality. Some of these deep learning models were found to have high performance when they were trained and tested on color retinal images with corresponding images from optical coherence tomography. The treatment of PCV is either a combination therapy using verteporfin photodynamic therapy and anti-vascular endothelial growth factor (VEGF), or anti-VEGF monotherapy, often used with a treat-and-extend regimen. New anti-VEGF agents may provide more durable treatment with similar efficacy, compared with existing anti-VEGF agents. It is not known if they can induce greater closure of polypoidal lesions, in which case, combination therapy may still be a mainstay. Recent evidence supports long-term follow-up of patients with PCV after treatment for early detection of recurrence, particularly in patients with incomplete closure of polypoidal lesions.

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“…[4][5][6] Some increased cytokine levels in plasma with a link of PCV or nAMD exclusively, suggesting that the 2 disorders may have different molecular mechanisms. 7,8 However, most existing studies on plasma markers of inflammation and angiogenesis in AMD rarely distinguish nAMD from PCV, even some kinds of cytokines in PCV or nAMD do not have altered levels of plasma compared to healthy controls; [9][10][11] while a recent study reported differences between plasma proinflammatory cytokines possessed a positive but weak ability in discriminating nAMD from PCV, indicating that PCV differed from nAMD in terms of plasma inflammation profile. 8 Therefore, the aim of this study was to further investigate markers of inflammation and angiogenesis in plasma of patients with PCV and nAMD and to identify differences in cytokine profiles between these diseases comprehensively.…”

Section: Introductionmentioning

confidence: 99%

Plasma Cytokine Profiles in Patients With Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration

Zhou

Zhao

Chen

2022

Asia-Pacific Journal of Ophthalmology

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Purpose: The concentrations of cytokines in plasma may be different between neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). We studied plasma levels of cytokines in patients with nAMD and PCV and compared them with control individuals. Methods: This was a prospective, clinic-based, case-control study of treatment-naive participants (n = 49) with PCV (n = 24), nAMD (n = 11), and cataract controls (n = 14). We sampled fresh venous blood and isolated plasma for analysis. Plasma concentrations of 34 angiogenic and inflammatory cytokines were determined by Luminex bead-based multiplex array. Results: After adjusting for gender and age using multivariate logistic analysis, we found that the plasma concentrations of monocyte chemoattractant protein-1, vascular endothelial growth factor (VEGF)-A, and VEGF-D significantly higher in both nAMD and PCV patients than those in controls (all P < 0.05, times in nAMD: 3.5, 4.3, and 13.8, respectively, times in PCV: 4.1, 4.0, and 11.5, respectively). In contrast, the plasma concentration of platelet-derived growth factor-BB was significantly lower in nAMD and PCV patients than those in controls (all P < 0.05, times in nAMD: 1.6, times in PCV: 1.7). The plasma levels of leukemia inhibitory factor in nAMD group were significantly higher compared with PCV group (P < 0.0167). Conclusions: Multiple cytokines involved in systemic inflammation and angiogenesis including monocyte chemoattractant protein-1, platelet-derived growth factor-BB, VEGF-A, and VEGF-D may contribute to the pathogenesis of nAMD and PCV. Measurement of leukemia inhibitory factor in the plasma may help differentiate nAMD from PCV. This finding suggests that the 2 disorders may have different molecular mechanisms, and additional longitudinal studies will be needed to determine whether these findings have clinical relevance to influence treatment algorithms or provide novel targets for medical therapy.

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Plasma Levels of Matrix Metalloprotease MMP-9 and Tissue Inhibitor TIMP-1 in Caucasian Patients with Polypoidal Choroidal Vasculopathy

Cited by 3 publications

References 33 publications

Serological cancer-associated protein biomarker levels at bowel endoscopy: Increased risk of subsequent primary malignancy

Serological cancer-associated protein biomarker levels at bowel endoscopy: Increased risk of subsequent primary malignancy

Polypoidal Choroidal Vasculopathy: Updates on Risk Factors, Diagnosis, and Treatments

Plasma Cytokine Profiles in Patients With Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration

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