Serum Insulin-like Growth Factor-binding Protein 7 Research Articles

Quantitative ultrasound techniques and biochemical markers to assess liver steatosis and fibrosis in newly diagnosed acromegaly.

The liver is known to be protected from steatosis under the influence of high GH/IGF-1. Cytokeratin 18 (CK18) and insulin-like growth factor binding protein 7 (IGFBP7) increase in liver steatosis and fibrosis. The aim of this study was to use quantitative ultrasound techniques and biochemical markers to assess liver steatosis and liver fibrosis in newly diagnosed acromegaly. This single-center, cross-sectional study included 23 patients with newly diagnosed acromegaly and 46 age, sex, body mass index (BMI) and waist circumference (WC)-matched controls. Liver steatosis was assessed using tissue attenuation imaging (TAI), and stiffness, indicative of fibrosis, was assessed by shear wave elastography (SWE). Serum IGFBP7 and CK18 were studied by ELISA. The acromegaly group had significantly lower liver steatosis (p = 0.006) and higher liver stiffness (p = 0.004), serum IGFBP7 (p = 0.048) and CK18 (p = 0.005) levels than the control group. The presence of fibrosis (p = 0.012) was significantly higher in the acromegaly group than in the control group. Moreover, CK18 was positively correlated with liver stiffness, WC, HOMA-IR, HbA1c, and triglyceride. In the acromegaly group, liver steatosis was negatively correlated with GH level. Stepwise multiple linear regression analysis revealed that BMI (p = 0.008) and CK18 (p = 0.015) were independent risk factors for increased liver stiffness. This study showed that there was an increased presence of liver fibrosis independent of liver steatosis in newly diagnosed acromegaly. Serum CK18 appears to be a potential marker of increased liver fibrosis in acromegaly.

The diagnostic value of serum insulin-like growth factor binding protein 7 in gastric cancer.

Early detection might help in reducing the burden and promoting the survival rate of gastric cancers. Herein, we tried to explore the diagnostic value of insulin-like growth factor binding protein 7 (IGFBP7) in gastric cancers. In this study, we first analyzed the expression levels and prognostic value of IGFBP7 mRNA in gastric cancers from The Cancer Genome Atlas (TCGA) database. Then, we recruited 169 gastric cancer patients and 100 normal controls as training cohort, and 55 gastric cancer patients and 55 normal controls as independent validation cohort. Enzyme-linked immunosorbent assay was applied to test the serum levels of IGFBP7. The receiver operating characteristic curve (ROC) and the area under the curve (AUC) were applied to evaluation the diagnostic value. TCGA showed that IGFBP7 mRNA was dysregulated and associated with prognosis in gastric cancer patients. Then, we examined the expression of serum IGFBP7 and found that serum IGFBP7 expressed lower in gastric cancer patients than normal controls both in training and independent validation cohorts (p < 0.0001). In training cohort, with the cutoff value of 1.515 ng/ml, the AUC for distinguishing gastric cancer patients was 0.774 (95% CI [0.713-0.836]) with sensitivity of 36.7% (95% CI [29.5-44.5]) and specificity of 90.0% (95% CI [82.0-94.8]). As for early-stage EJA, the AUC was 0.773 (95% CI [0.701-0.845]) with the sensitivity of 33.3% (95% CI [14.4-58.8]). In independent validation cohort, with the same cutoff value, the AUC reached to 0.758 (95% CI [0.664-0.852]). Similarly, for early-stage gastric cancer diagnosis in the independent validation cohort, the AUC value was 0.778 (95% CI [0.673-0.882]). This study indicated that serum IGFBP7 might act as a potential early diagnostic marker for gastric cancers.

Diagnostic Potential of Two Novel Biomarkers for Neuromyelitis Optica Spectrum Disorder and Multiple Sclerosis.

Currently, no tests can definitively diagnose and distinguish neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS). Initially, cerebrospinal fluid (CSF) proteomics were employed to uncover the novel biomarkers that differentiate NMOSD from MS into cohorts of 10 MS and 10 NMOSD patients. Subsequently, screening biomarkers were validated using an enzyme-linked immunosorbent assay method and CSF and serum samples from 20 MS patients, 20 NMOSD patients, 20 non-inflammatory neurological controls, and 20 healthy controls. In study cohort, insulin-like growth factor-binding protein 7 (IGFBP7) and lysosome-associated membrane glycoprotein 2 (LAMP2) were screened. In validation cohort, serum and CSF IGFBP7 not only exhibited higher levels in MS and NMOSD patients than controls, but also had greatest area under the curve (AUC, above or equal to 0.8) in MS and NMOSD diagnoses. Serum IGFBP7 (0.945) and CSF IGFBP7 (0.890) also had the greatest AUCs for predicting MS progression, while serum LAMP2 had a moderate curve (0.720). IGFBP7 was superior in diagnosing MS and NMOSD, and IGFBP7 and serum LAMP2 performed exceptionally well in predicting the MS progression. These results offered reasons for further investigations into the functions of IGFBP7 and LAMP2 in MS and NMOSD.

Serum Insulin-Like Growth Factor-Binding Protein 7 Deriving from Spleen and Lung Could Be Used for Early Recognition of Cardiac Surgery-Associated Acute Kidney Injury

Introduction: The utility of arithmetic product of urinary tissue metalloproteinase inhibitor 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7) concentrations has been widely accepted on early diagnosis of acute kidney injury (AKI). However, which organ is the main source of those two factors and how the concentration of IGFBP7 and TIMP2 changed in serum during AKI still remain to be defined. Methods: In mice, gene transcription and protein levels of IGFBP7/TIMP2 in the heart, liver, spleen, lung, and kidney were measured in both ischemia-reperfusion injury (IRI)- and cisplatin-induced AKI models. Serum IGFBP7 and TIMP2 levels were measured and compared in patients before cardiac surgery and at inclusion (0 h), 2 h, 6 h, and 12 h after intensive care unit (ICU) admission, and compared with serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and serum uric acid (UA). Results: In mouse IRI-AKI model, compared with the sham group, the expression levels of IGFBP7 and TIMP2 did not change in the kidney, but significantly upregulated in the spleen and lung. Compared with patients who did not develop AKI, the concentration of serum IGFBP7 at as early as 2 h after ICU admission (sIGFBP7-2 h) was significantly higher in patients who developed AKI. The relationships between sIGFBP7-2 h in AKI patients and log₂ (SCr), log₂ (BUN), log₂ (eGFR), and log₂ (UA) were statistically significant. The diagnostic performance of sIGFBP7-2 h measured by the macro-averaged area under the receiver operating characteristic curve was 0.948 (95% CI, 0.853–1.000; p < 0.001). Conclusion: The spleen and lung might be the main source of serum IGFBP7 and TIMP2 during AKI. The serum IGFBP7 value demonstrated good predictive accuracy for AKI following cardiac surgery within 2 h after ICU admission.

INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-7 AS A MARKER OF CARDIAC REVERSE REMODELING WITH EMPAGLIFLOZIN: A SECONDARY ANALYSIS OF THE EMPA-HEART CARDIOLINK-6 RANDOMIZED CONTROLLED TRIAL

Reverse cardiac remodeling is believed to contribute to the cardiovascular benefits offered by sodium-glucose transport protein 2 inhibitors (SGLT2i). Given the association between insulin-like growth factor binding protein 7 (IGFBP7) levels and cardiac remodeling, it has been postulated that IGFBP7 may serve as a predictor for individuals who may derive greater benefit from SGLT2i therapy. This exploratory sub-analysis of the EMPA-HEART CardioLink-6 trial examined the association between serum IGFBP7 levels and reverse cardiac remodeling in patients treated with empagliflozin.

IGFBP7 is a predictor of diuretic-induced acute kidney injury in the patients with acute decompensated heart failure

Abstract Objectives The serum Insulin-like growth factor-binding protein 7 (IGFBP7) levels were tested to predict acute renal damage that may develop in patients with stage III–IV heart failure who were treated with intravenous diuretics in the emergency department. Method Patients with stage III–IV heart failure (n=84) were included in this prospective observational study. All patients were treated with IV diuretic therapy in accordance with a predetermined protocol. The serum IGFBP7 and creatinine levels were analyzed at the beginning of the treatment (0 h), 6th, and 12th hours. The creatinine level and glomerular filtration rate (GFR) at baseline were compared with the 12th hour values. The results were classified according to the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria for each patient. The patients were divided into two groups as those in any RIFLE group (RIFLE (+)) and those without (RIFLE (−)). The groups were compared in terms of IGFBP7 levels. Results and Discussion 0, 6th, and 12th hour levels of IGFBP7 were significantly different between the RIFLE + and RIFLE – groups. (p=0.036, 0.042, and 0.006, respectively). The IGFBP7 levels were higher in RIFLE (+) group. However, the IGFBP7 values did not increase with time. In the ROC curve analyze for IGFBP7 levels, the cutoff with the highest sum of sensitivity (0.80) and specificity (0.69) was 118.71. Conclusions The serum IGFBP7 levels can predict the risk of developing AKI before the diuretic treatment in the patients with stage III–IV heart failure.

Renal Impairment Detectors: IGFBP-7 and NGAL as Tubular Injury Markers in Multiple Myeloma Patients.

Background and Objectives: Urine insulin-like growth factor-binding protein 7 (IGFBP-7), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and neutrophil gelatinase-associated lipocalin (NGAL) monomer are novel tubular kidney injury biomarkers. In multiple myeloma (MM), immunoglobulin free light chains (FLCs) play an integral role in renal impairment. This study aimed to investigate the correlation between new biomarkers and acclaimed parameters of renal failure, MM stage, and prognosis. Materials and Methods: The examined parameters included: urinary and serum cystatin-C, IGFBP-7, and TIMP-2, and urinary NGAL monomer in 124 enrolled patients. Results: Urinary and serum IGFBP-7 and urinary NGAL were higher among patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and positively correlated with urine light chains. Serum and urine IGFBP-7 and urine NGAL were greater among patients with a higher disease stage. In the whole study group, urinary concentrations of the studied markers were positively correlated with each other. In multiple linear regression, urinary IGFBP-7 and NGAL were associated with lower eGFR, independently of other urinary markers. Conclusions: Urinary IGFBP-7 and NGAL monomer may be useful markers of tubular renal damage in patients with MM. Biomarker-based diagnostics may contribute to earlier treatment that may improve renal outcomes and life expectancy in MM.

Diagnostic Value of Serum Insulin-Like Growth Factor Binding Protein 7 (IGFBP7) in Colorectal Cancer.

PurposeHigh serum insulin-like growth factor binding protein-7 (IGFBP-7) has been found in several malignant tumors. Here, we aimed to assess the diagnostic potential of serum IGFBP7 in patients with colorectal cancer (CRC).Patients and MethodsAn enzyme-linked immunosorbent assay (ELISA) was performed to detect IGFBP7 level in the serum of 115 CRC patients and 107 healthy controls, and receiver operating characteristics (ROC) was used to evaluate the accuracy of diagnosis.ResultsThe levels of serum IGFBP7 were significantly higher in CRC than those in normal controls (P < 0.001). With optimized cutoff of 2.050 ng/mL, IGFBP7 showed certain diagnostic value with specificity of 93.9%, sensitivity of 64.5% and an area under the curve (AUC) of 0.815 (95% CI: 0.754–0.877) in CRC. In early-stage CRC, IGFBP7 provided an AUC of 0.826 (95% CI: 0.757–0.896), a sensitivity of 64.5%, and a specificity of 95.8%. Furthermore, when compared with carcinoembryonic antigen (CEA), the accuracy of serum IGFBP7 in the diagnosis of CRC and early-stage CRC were significantly improved. Analysis of clinical data shows that there are no significant differences between IGFBP7 and clinical factors.ConclusionOur study suggested that serum IGFBP7 might serve as a potential biomarker for early-stage CRC diagnosis.

Serum Insulin-Like Growth Factor Binding Protein 7 as a Potential Biomarker in the Diagnosis and Prognosis of Esophagogastric Junction Adenocarcinoma.

Background/AimsEsophagogastric junction adenocarcinoma (EJA) is a malignant tumor associated with high morbidity and has attracted increasing attention due to a rising incidence and low survival rate. Pathological biopsy is the gold standard for diagnosis, but noninvasive and effective tests are lacking, resulting in diagnoses at advanced stages. This study explored the diagnostic value of insulin-like growth factor binding protein 7 (IGFBP7) in EJA.MethodsA total of 120 EJA patients and 88 normal controls were recruited, and their serum levels of IGFBP7 were measured by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value, and Pearson chi-square analysis was used to evaluate the correlation between IGFBP7 and clinical parameters. Kaplan-Meier survival analysis was carried out to assess the effect of IGFBP7 on overall survival (OS).ResultsThe levels of IGFBP7 were higher in both early- and late-stage EJA patients than in normal controls (p<0.001). The area under the ROC curve for EJA patients was 0.794 (95% confidence interval [CI], 0.733 to 0.854), with a cutoff value of 2.716 ng/mL, a sensitivity of 63.3% (95% CI, 54.0% to 71.8%) and a specificity of 90.9% (95% CI, 82.4% to 95.7%). For the diagnosis of early-stage EJA, the same cutoff value and specificity were obtained, but the sensitivity of IGFBP7 was 54.3% (95% CI, 36.9% to 70.8%). Patients with low IGFBP7 protein expression had lower OS than those with high expression (p=0.034). The multivariate analysis showed that IGFBP7 is an independent prognostic factor for EJA (p=0.011).ConclusionsSerum IGFBP7 acts as a potential diagnostic and prognostic marker for EJA.

IGFBP7 Drives Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibition in Lung Cancer.

Patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer show a dramatic response to EGFR-tyrosine kinase inhibitors (TKIs). However, acquired drug resistance eventually develops. This study explored the novel mechanisms related to TKI resistance. To identify the genes associated with TKI resistance, an integrative approach was used to analyze public datasets. Molecular manipulations were performed to investigate the roles of insulin-like growth factor binding protein 7 (IGFBP7) in lung adenocarcinoma. Clinical specimens were collected to validate the impact of IGFBP7 on the efficacy of EGFR TKI treatment. IGFBP7 mRNA expression in cancer cells isolated from malignant pleural effusions after acquired resistance to EGFR-TKI was significantly higher than in cancer cells from treatment-naïve effusions. IGFBP7 expression was markedly increased in cells with long-term TKI-induced resistance compared to in TKI-sensitive parental cells. Reduced IGFBP7 in TKI-resistant cells reversed the resistance to EGFR-TKIs and increased EGFR-TKI-induced apoptosis by up-regulating B-cell lymphoma 2 interacting mediator of cell death (BIM) and activating caspases. Suppression of IGFBP7 attenuated the phosphorylation of insulin-like growth factor 1 receptor (IGF-IR) and downstream protein kinase B (AKT) in TKI-resistant cells. Clinically, higher serum IGFBP7 levels and tumors with positive IGFBP7-immunohistochemical staining were associated with poor TKI-treatment outcomes. IGFBP7 confers resistance to EGFR-TKIs and is a potential therapeutic target for treating EGFR-TKI-resistant cancers.

The Diagnostic Value of Serum IGFBP7 in Patients with Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell cancer (ESCC) is one of the leading malignant cancer in the world and especially in China with high incidence and mortality. The exploration of novel serum biomarkers is required for early detection of ESCC. We investigated the diagnostic value of serum insulin like growth factor binding protein 7 (IGFBP7) in ESCC, evaluating its potential to improve the diagnosis of ESCC. The serum samples of 106 patients with ESCC and 107 normal controls were tested by enzyme-linked immunosorbent assay (ELISA). The levels of IGFBP7 in ESCC group were significantly higher than that in normal controls, compared by the Mann-Whitney U test (P<0.0001). Using receiver operating characteristic (ROC) curve, the diagnostic value of serum IGFBP7 was demonstrated. Versus normal group, the area under the ROC curve (AUC) of all ESCC was 0.794 (95%CI: 0.735-0.853) and early-stage ESCC was 0.725 (95%CI: 0.633-0.817). With optimized cutoff value of 2.993 ng/mL, IGFBP7 showed certain diagnostic value with specificity of 90.7%, sensitivities of 40.6% and 32.4% in ESCC and early-stage ESCC, respectively. Considering the correlation between clinical data and IGFBP7, no significant association was found (all P>0.05). Thus, we supposed that serum IGFBP7 might be a potential biomarker in the diagnosis of ESCC.

Serum and urine FGF23 and IGFBP-7 for the prediction of acute kidney injury in critically ill children

BackgroundFibroblast growth factor 23 (FGF23) and insulin-like growth factor binding protein 7 (IGFBP-7) are suggested to be biomarkers for predicting acute kidney injury (AKI). We compared them with proposed AKI biomarker of cystatin C (CysC), and aimed (1) to examine whether concentrations of these biomarkers vary with age, body weight, illness severity assessed by pediatric risk of mortality III score, and kidney function assessed by estimated glomerular filtration rate (eGFR), (2) to determine the association between these biomarkers and AKI, and (3) to evaluate whether these biomarkers could serve as early independent predictors of AKI in critically ill children.MethodsThis prospective single center study included 144 critically ill patients admitted to the pediatric intensive care unit (PICU) regardless of diagnosis. Serum and spot urine samples were collected during the first 24 h after PICU admission. AKI was diagnosed based on the AKI network (AKIN) criteria.ResultsTwenty-one patients developed AKI within 120 h of sample collection, including 11 with severe AKI defined as AKIN stages 2 and 3. Serum FGF23 levels were independently associated with eGFR after adjustment in a multivariate linear analysis (P < 0.001). Urinary IGFBP-7 (Adjusted OR = 2.94 per 1000 ng/mg increase, P = 0.035), serum CysC (Adjusted OR = 5.28, P = 0.005), and urinary CysC (Adjusted OR = 1.13 per 1000 ng/mg increase, P = 0.022) remained significantly associated with severe AKI after adjustment for body weight and illness severity, respectively. Urinary IGFBP-7 level was predictive of severe AKI and achieved the AUC of 0.79 (P = 0.001), but was not better than serum (AUC = 0.89, P < 0.001) and urinary (AUC = 0.88, P < 0.001) CysC in predicting severe AKI.ConclusionsSerum FGF23 levels were inversely related to measures of eGFR. In contrast to serum and urinary FGF23 which are not associated with AKI in a general and heterogeneous PICU population, an increased urinary IGFBP-7 level was independently associated with the increased risk of severe AKI diagnosed within the next 5 days after sampling, but not superior to serum or urinary CysC in predicting severe AKI in critically ill children.

Circulating cell-free DNA of methylated insulin-like growth factor-binding protein 7 predicts a poor prognosis in hepatitis B virus-associated hepatocellular carcinoma after hepatectomy

The initiation and progression of hepatocellular carcinoma (HCC) is a multistage process involving a variety of changes at the gene level. Methylation of insulin-like growth factor-binding protein 7 (IGFBP7) plays a crucial role in HCC development. The main purpose of this study was to investigate the relationship between oxidative stress, DNA methyltransferases (DNMTs) expression, and IGFBP7 methylation, and to evaluate the prognostic value of serum IGFBP7 methylation status in patients with HCC after hepatectomy. We enrolled 155 patients with HCC undergoing surgical resection. The IGFBP7 methylation status, DNMTs mRNA levels and malondialdehyde (MDA), xanthine oxidase (XOD), reduced glutathione hormone (GSH), and glutathione-S-transferases (GST) levels were detected. MDA and XOD levels were significantly higher in IGFBP7 methylated group than unmethylated group, while GSH level was lower in methylated group than unmethylated group. The DNMT1 and DNMT3a mRNA levels were higher in IGFBP7 methylated group than unmethylated group. Kaplan–Meier curve analysis revealed that IGFBP7 promoter methylation was significantly correlated with overall survival (OS) (p < .001). Moreover, IGFBP7 methylation was an independent prognostic predictor for OS (p = .000) and early tumour recurrence (ETR) (p = .008) in HCC after hepatectomy. Our results indicated that IGFBP7 promoter methylation was associated with oxidative stress and DNMTs expression. Meanwhile, IGFBP7 promoter methylation was associated with OS and ETR, indicating that it might serve as a potentially independent prognostic factor in patients with HCC after hepatectomy.

Comparison of Prognostic Usefulness of Serum Insulin-Like Growth Factor-Binding Protein 7 in Patients With Heart Failure and Preserved Versus Reduced Left Ventricular Ejection Fraction

We aimed to characterize of the role of insulin-like growth factor-binding protein 7 (IGFBP-7) in heart failure (HF) pathophysiology. IGFBP-7 has been associated with cardiac hypertrophy and diastolic dysfunction in HF. In 86 patients with HF with a preserved ejection fraction (HFpEF) (ejection fraction [EF] ≥45%) and 79 with HF with a reduced ejection fraction (HFrEF), we assessed concentrations of serum IGFBP-7, correlations between serum IGFBP-7 and clinical data, diastolic function, and associations with outcome. IGFBP-7 was lower in HFpEF than HFrEF (102 vs 152 µg/L, p <0.001) and correlated with New York Heart Association class (HFpEF: r = 0.25, p = 0.020; HFrEF: r=0.26, p = 0.022), N-terminal pro-brain natriuretic peptide (NT-proBNP) (HFpEF: r = 0.53, p <0.001; HFrEF: r = 0.50, p <0.001), and estimated glomerular filtration rate (eGFR) (HFpEF: r = -0.47, p <0.001; HFrEF: r = -0.45, p <0.001). In HFpEF, IGFBP-7 correlated with E/e' (r = 0.31, p = 0.012) and E/A ratio (r = 0.31, p = 0.011). In HFrEF, but not HFpEF, IGFBP-7 correlated with age (r = 0.29, p = 0.009) and atrial fibrillation (r = 0.34, p = 0.002). IGFBP-7 predicted the outcome in HFpEF (hazard ratio 4.19 [1.01 to 17.35], p = 0.048]) but not in HFrEF (0.72 [0.24 to 2.14], p = 0.554). In conclusion in HFrEF, IGFBP-7 was elevated and associated with HF severity but not prognostic, suggesting a marker of risk. In HFpEF, IGFBP-7 was less elevated but associated with markers of diastolic dysfunction, HF severity, and prognosis. IGFBP-7 may contribute to the progression of HFpEF possibly through inflammation and oxidative stress.

Combined detection of insulin-like growth factor-binding protein 7 promoter methylation improves the diagnostic efficacy of AFP in hepatitis B virus-associated hepatocellular carcinoma

This study quantitatively assessed serum insulin-like growth factor-binding protein 7 (IGFBP7) promoter methylation in hepatocellular carcinoma (HCC), and explored its clinical value. A total of 80 patients with hepatitis B virus-associated HCC, 35 patients with chronic hepatitis B (CHB), and 20 healthy controls (HC) were enrolled. MethyLight was used to quantitatively assess the methylation levels of serum IGFBP7 promoter. A logistic regression model was established for the combined evaluation of AFP and serum IGFBP7 promoter methylation. The results showed that mean methylation levels of serum IGFBP7 promoter were significantly higher in HCC (5.33%, interquartile range [IQR] 1.14–15.70%) patients than in individuals with CHB (1.54%, IQR 0.64–2.45%; P<0.01) and HC (0.63%, IQR 0.22–0.98%; P<0.01). In HCC subgroups, patients with vascular invasion, tumor size >3cm and advanced tumor node metastasis (TNM) showed higher methylation levels compared with the remaining groups (P<0.05). Compared with AFP alone, combined determination based on logistic regression analysis significantly improved the area under the receiver operating characteristic (ROC) curve (AUC) (0.759 vs 0.623, P<0.05). In addition, the Youden index was increased from 5.71%, 11.25% and 15.18%, when considering AFP alone at cut-off values of 20, 200, and 400ng/ml, respectively, to 45.71% with IGFBP7 promoter methylation taken into consideration (all P<0.05). These results suggested that combined quantitative measurement of serum IGFBP7 promoter methylation could enhance the diagnostic ability of AFP in distinguishing hepatitis B virus-associated HCC from CHB.

Serum levels of IGFBP7 are elevated during acute exacerbation in COPD patients.

ObjectiveThe purpose of this study was to explore the insulin-like growth factor binding protein 7 (IGFBP7) level in the serum of chronic obstructive pulmonary disease (COPD) patients during acute exacerbation (AE).MethodsThe study population consisted of 47 AECOPD patients, including 25 patients enrolled between January 2011 and February 2011 (the first group) and 22 patients enrolled from December 2011 to August 2012 (the second group) and 29 healthy controls. Chemiluminescence–linked immunoassay was used to detect serum IGFBP7 levels. For the second group patients, IGFBP7 and C-reactive protein (CRP) levels were measured both on the admission day and on the discharge day.ResultsAmong the first group AECOPD patients, serum IGFBP7 levels were significantly elevated in AECOPD patients in the intensive care unit (ICU; 52.92±16.32 ng/mL), and in hospitalized AECOPD patients not in ICU (40.66±13.9), compared to healthy subjects (30.3±7.09 ng/mL; P<0.01). For the second group AECOPD patients, the increased IGFBP7 levels reduced after the patients had recovered (34.42±11.88 vs 27.24±7.2 ng/mL; P<0.01). During AE, the correlation coefficient between IGFBP7 and CRP was 0.357. In receiver operating characteristic analysis, the area under the curve was 0.799 for CRP, and 0.663 for IGFBP7 in distinguishing patients with AECOPD on the admission day from the discharge day.ConclusionSerum IGFBP7 levels were raised during AECOPD. Similar to the expression pattern of CRP, the IGFBP7 levels reduced after convalescence, suggesting that IGFBP7 might have a candidate role as a biomarker of AECOPD. No significant linear correlation was detected between IGFBP7 and CRP, indicating the probable different role for the two molecules in assessing AECOPD. Further study is needed to explore the value of IGFBP7 in differentiating phenotypes of AECOPD.

Serum insulin-like growth factor-1 and its binding protein-7: potential novel biomarkers for heart failure with preserved ejection fraction.

BackgroundInsulin-like growth factor binding protein-7 (IGFBP-7) modulates the biological activities of insulin-like growth factor-1 (IGF-1). Previous studies demonstrated the prognostic value of IGFBP-7 and IGF-1 among patients with systolic heart failure (HF). This study aimed to evaluate the IGF1/IGFBP-7 axis in HF patients with preserved ejection fraction (HFpEF).MethodsSerum IGF-1 and IGFBP-7 levels were measured in 300 eligible consecutive patients who underwent comprehensive cardiac assessment. Patients were categorized into 3 groups including controls with normal diastolic function (n = 55), asymptomatic left ventricular diastolic dysfunction (LVDD, n = 168) and HFpEF (n = 77).ResultsIGFBP-7 serum levels showed a significant graded increase from controls to LVDD to HFpEF (median 50.30 [43.1-55.3] vs. 54.40 [48.15-63.40] vs. 61.9 [51.6-69.7], respectively, P < 0.001), whereas IGF-1 levels showed a graded decline from controls to LVDD to HFpEF (120.0 [100.8-144.0] vs. 112.3 [88.8-137.1] vs. 99.5 [72.2-124.4], p < 0.001). The IGFBP-7/IGF-1 ratio increased from controls to LVDD to HFpEF (0.43 [0.33-0.56] vs. 0.48 [0.38-0.66] vs. 0.68 [0.55-0.88], p < 0.001). Patents with IGFB-7/IGF1 ratios above the median demonstrated significantly higher left atrial volume index, E/E’ ratio, and NT-proBNP levels (all P ≤ 0.02).ConclusionIn conclusion, this hypothesis-generating pilot study suggests the IGFBP-7/IGF-1 axis correlates with diastolic function and may serve as a novel biomarker in patients with HFpEF. A rise in IGFBP-7 or the IGFBP-7/IGF-1 ratio may reflect worsening diastolic function, adverse cardiac remodeling, and metabolic derangement.

Evaluation of IGFBP-7 DNA methylation changes and serum protein variation in Swedish subjects with and without type 2 diabetes

BackgroundInsulin-like growth factor-binding protein 7 (IGFBP-7) is able to interact with insulin-like growth factor 1 (IGF-1) as well as insulin. Previous studies have suggested that serum IGFBP-7 levels may be associated with insulin resistance in type 2 diabetes (T2D). This study aimed to evaluate IGFBP-7 serum protein and IGFBP7 DNA methylation levels in the subjects with and without T2D.ResultsA total of 340 Swedish subjects including 100 newly diagnosed T2D patients (50 women/50 men), 100 age-matched nondiabetic control subjects (50/50) and 140 treated T2D patients (54/86) were studied. Serum IGFBP-7 levels were measured with a novel ELISA. IGF1, IGFBP-1, and insulin were determined by in-house radioimmunoassays. DNA methylation levels in the IGFBP7 gene were analyzed with a bisulfite-pyrosequencing technique. Serum IGFBP-7 protein levels were similar among nondiabetic subjects, newly diagnosed, and treated T2D patients and were not correlated with IGFBP7 DNA methylation. However, IGFBP7 DNA methylation was increased in men with newly diagnosed T2D compared with nondiabetic controls (17.6% vs. 12.5%, P < 0.01). Serum IGFBP-7 levels correlated (r = 0.331, P = 0.019) with serum IGFBP-1 levels, a marker of insulin production, in men but not women with newly diagnosed T2D.ConclusionsThis study demonstrates for the first time that IGFBP7 DNA methylation levels are increased in Swedish men with newly diagnosed T2D. The correlation between IGFBP-7 and IGFBP-1 suggests that low IGFBP-7 may be associated with insulin resistance in T2D.

Methylation of serum insulin‐like growth factor‐binding protein 7 promoter in hepatitis B virus‐associated hepatocellular carcinoma

Methylation of gene promoter CpG islands is an important early event in hepatocellular carcinoma (HCC), and detection of cell-free tumor-specific DNA methylation is becoming a useful noninvasive method for HCC. This study was aimed at determining the diagnostic value of serum insulin-like growth factor-binding protein 7 (IGFBP7) promoter methylation in hepatitis B virus-associated HCC. A total of 217 subjects, including 136 HCC patients, 46 patients with chronic hepatitis B (CHB), and 35 healthy controls (HCs), were included. The methylation status of the serum IGFBP7 gene promoter was determined using methylation-specific PCR. The frequency of serum IGFBP7 promoter methylation in HCC patients (89/136, 65%) was significantly higher than that in CHB patients (8/46, 17%; X(2) = 31.883, P < 0.001) and HCs (5/35, 14%; X(2) = 29.429, P < 0.001). Moreover, elevated IGFBP7 methylation frequency was also observed in HCC patients with vascular invasion compared with those without vascular invasion (84 versus 60%, X(2) = 6.633, P = 0.010). The sensitivities of serum IGFBP7 methylation and alpha-fetoprotein (AFP) in detecting HCC were 65 and 57%, respectively. Of note, the combination of IGFBP7 methylation and AFP showed 85% for sensitivity. These results suggest that methylation of the serum IGFBP7 gene promoter may serve as a useful noninvasive biomarker for HCC diagnosis.