Serum Galectin-3 Research Articles

Circulating Galectin-3: A Prognostic Biomarker in Hepatocellular Carcinoma.

Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC. We prospectively enrolled and collected clinicopathologic data and serum samples from 767 patients with HCC between 2001 and 2014 at The University of Texas MD Anderson Cancer Center. Two hundred patients without HCC were also enrolled and had data collected. The Kaplan-Meier method was used to estimate overall survival (OS) distributions. The median OS in this cohort was 14.2 months (95% CI, 12-16.1). At the time of analysis, the 1-year OS rate was 45% (95% CI, 0.4-0.51) among patients with high galectin-3 levels and 59% (95% CI, 0.54-0.63) among patients with low galectin-3 levels. OS was significantly inferior in patients with high galectin-3 levels than in patients with lower galectin-3 levels (median OS: 10.12 vs. 16.49 months; p = 0.0022). Additionally, the multivariate model showed a significant association between high galectin-3 level and poor OS (hazard ratio [HR] = 1.249; 95% CI, 1.005-1.554). Comparison between low ( n = 464 patients) and high ( n = 302 patients) galectin-3 levels showed that mean serum galectin-3 levels were significantly higher in patients with HCC who had hepatitis C virus (HCV) infection ( p = 0.0001), higher Child-Pugh score (CPS) ( p = 0.0009), and higher Cancer of the Liver Italian Program (CLIP) score ( p = 0.0015). Our study shows that serum galectin-3 level is a valid prognostic biomarker candidate.

Higher Serum Galectin‑3 Levels Were Associated with More Severe Motor Performance in Parkinson's Disease.

Parkinson's disease (PD) is a movement disorder that lacks proven biomarkers. Case-control genome-wide association studies revealed the potential effect of galectin‑3 (GAL3) on motor progression in PD patients. Based on this finding, our study aimed to explore the correlation between serum GAL3 levels and motor performance in PD patients. Five hundred PD patients and 200healthy controls were recruited. The serum levels of GAL3 were measured in participants by enzyme linked immunosorbent assay (ELISA). The baseline characteristics of the participants were collected, and the associated scale scores were obtained. Compared with healthy controls, the serum levels of GAL3 were greatly increased in PD patients. These levels could distinguish between PD patients and healthy controls with a sensitivity of 0.798 and a specificity of 0.815 (AUC = 0.795, 95% CI 0.757-0.834, P < 0.001). Patients with age >60 years tended to have higher serum GAL3 levels, disease duration, Hoehn-Yahr stage, MDS-UPDRS III total score, tremor subscores, rigid subscores, and bradykinesia subscores than those with age ≤60 years. When adjusting for confounders, higher GAL3 level was significantly correlated with MDS-UPDRS III total score and rigid subscores. In men with PD, GAL3 was significantly correlated with MDS-UPDRS III total score; but the association between GAL3 and bradykinesia subscores was found in women. Moreover, the associations between GAL3 with MDS-UPDRS III total score and bradykinesia subscores were significant in patients with age >60 years. Higher GAL3 level was related to more severe motor performance in patients with age >60 years, and it may be a potential predictive biomarker for motor performance in PD patients.

Galectin-3 and cancer mortality in patients with suspected or known coronary artery disease: the ANOX study

Abstract Background Galectin-3 is a multifunctional carbohydrate-binding lectin that is involved in inflammation, tissue remodeling, and fibrosis. High circulating levels of galectin-3 are associated with all-cause mortality, cardiovascular (CV) mortality, and/or major adverse CV events in patients with CV diseases such as heart failure and coronary artery disease (CAD). However, the associations of galectin-3 with non-CV mortality and cancer mortality in patients with suspected or known CAD are unknown. Methods Serum galectin-3 levels were measured in 2,418 patients with suspected or known CAD undergoing elective coronary angiography. The outcomes were all-cause death, CV death, non-CV death, cancer death, and other non-CV death. Patients were followed up over a 6-year period. Results During the follow-up, 536 (22.2%) deaths occurred, including 166 (6.9%) CV deaths, 326 (13.5%) non-CV deaths, 128 (5.3%) cancer deaths, 198 (8.2%) other non-CV deaths, and 44 (1.8%) undetermined deaths. After adjustment for potential clinical confounders (i.e., age, sex, body mass index, hypertension, dyslipidemia, diabetes, current smoker, estimated glomerular filtration rate, the Gensini score, previous myocardial infarction, previous stroke, previous heart failure hospitalization, atrial fibrillation, valvular heart disease, malignancies, anemia, antihypertensive drug use, statin use, and aspirin use) and established CV biomarkers (i.e., N-terminal pro-brain natriuretic peptide, high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein), galectin-3 levels were significantly associated with all-cause death (hazard ratio [HR] for 1-SD increase, 1.22; 95% confidence interval [CI], 1.13–1.31), CV death (HR, 1.16; 95% CI, 1.02–1.33), non-CV death (HR, 1.27; 95% CI, 1.15–1.40), cancer death (HR, 1.31; 95% CI, 1.07–1.61), and other non-CV death (HR, 1.30; 95% CI, 1.15–1.46). The addition of galectin-3 levels to the model with potential clinical confounders and established CV biomarkers significantly improved the prediction of all-cause death (P&amp;lt;0.001 for continuous net reclassification improvement [NRI], P&amp;lt;0.001 for integrated discrimination improvement [IDI]) and cancer death (P=0.001 for NRI, P=0.005 for IDI), but not that of CV death (P=0.601 for NRI, P= 0.708 for IDI), non-CV death (P=0.060 for NRI, P=0159 for IDI), or other non-CV death (P=0.266 for NRI, P=0.699 for IDI). Conclusions The galectin-3 level independently predicted all-cause mortality and cancer mortality in patients with suspected or known CAD.

Serum Galectin-3 Level in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial tissue transformation and fibroblast-like synoviocyte (FLS) proliferation. Galectin-3 is gaining attention as a diagnostic and prognostic biomarker for RA diagnosis. Elevated levels of Galectin-3 cause RA[1]FLSs to stimulate and generate proinflammatory agents, contributing to cartilage degradation and osteoclast formation. This systematic review and meta-analysis aimed to evaluate published evidence and support future investigation of Galectin-3 as an early biomarker for RA. A systematic search was performed through four databases, including PubMed, the Web of Science, Scopus, and Embase, to find the studies examining Galectin-3 in individuals with RA compared to healthy controls. The risk of bias was evaluated using the Newcastle-Ottawa Quality Assessment Scale. Random-effects meta-analysis comparing serum/plasma Galectin-3 levels between individuals with RA and healthy control groups was performed to determine the standardized mean differences (SMD) along with 95% confidence intervals. Following the initial search, studies went through screening. 12 studies, involving 773 patients with RA and 411 healthy controls, were included. Meta-analysis of the included studies revealed that individuals with RA had significantly higher levels of circulatory Galectin-3 compared to healthy control groups (SMD 0.957, 95% CI 0.393 to 1.520). Univariable meta-regression showed no significant association between age, publication year, sample size, or the male percentage with effect size. According to the results, Galectin-3 might be useful as a biomarker for RA. To support these findings, further investigations of Galectin-3 as a possible early biomarker of RA is necessary.

Usefulness of Galectin-3 as a Biochemical Marker to Detect Ventricular and Supraventricular Arrhythmias in Children.

Galectin-3 (Gal-3) has been demonstrated to play a pivotal role in the pathogenesis of several fibrotic disorders. A number of studies have examined the relationship between galectin-3 levels and cardiac fibrosis in heart failure. Nevertheless, the role of galectin-3 in the etiology of supraventricular (SVa) and ventricular (Va) arrhythmias remains largely unexamined. The objective of this prospective study was to investigate the potential correlation between galectin concentration and the occurrence of idiopathic cardiac arrhythmias in pediatric patients. Biochemistry analysis was performed on 30 children (11-18 years; 14 boys and 16 girls). The control group consisted of 20 children. Cardiac arrhythmia was confirmed by a 24 h Holter ECG recording. Serum galectin-3 levels were measured via enzyme-linked immunosorbent assay (ELISA). Statistical analysis of the data showed significant associations between creatinine kinase (CK) and Gal-3 in patients with SVa (SVT-supraventricular tachycardia) arrhythmias, suggesting a potential effect of CK on Gal-3 levels. However, no correlation was identified between Gal-3 concentration and the occurrence of cardiac arrhythmias under investigation. We concluded that galectin-3 does not have the potential to be a biomarker in the diagnosis of idiopathic arrhythmias in pediatric patients.

Serum galectin-3 and fibroblast growth factor-23 levels in relation with type 2 diabetes and cardiovascular risk

Serum galectin-3 and fibroblast growth factor-23 levels in relation with type 2 diabetes and cardiovascular risk

Association Between Serum Galectin-3 and Parkinson's Disease: A Two-Sample Mendelian Randomization Study.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder with poor prognosis. Observational studies have demonstrated a significant correlation between serum galectin-3 and PD, suggesting a potential role of galectin-3 as a biomarker for PD. However, it is still unclear whether galectin-3 contributes to the risk of the disease. A two-sample Mendelian randomization (MR) approach was used in this study. Genetic instruments for serum galectin-3 level were selected from a genome-wide association study (GWAS), including 30,931 European individuals. Summary-level statistics for PD were derived from another published GWAS, including 33,674 cases and 449,056 controls. Primary analysis was conducted using the inverse-variance weighting (IVW) method. Weighted median, MR-Egger, simple mode, weighted mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods were used as complementary analyses. To detect heterogeneity, Cochran's Q statistic and leave-one-out analysis were used. For testing potential horizontal pleiotropy, the MR-Egger intercept test and MR-PRESSO global test were conducted. MR analysis using IVW model (OR 1.112, 95% CI 1.025-1.206, p = 0.010), weighted median (OR 1.135, 95% CI 1.037-1.242, p = 0.006), weighted mode (OR 1.142, 95% CI 1.038-1.257, p = 0.030), and MR-PRESSO (OR 1.112, 95% CI 1.046-1.182, p = 0.012) presented a consistent result, indicating that increased serum galectin-3 was associated with a higher risk of PD. No heterogeneity or horizontal pleiotropy was detected in the analyses. The study shows a suggestive association between galectin-3 and PD. Increasing serum galectin-3 was associated with an increase in PD risk. Galectin-3 may play an important role in the causal pathway to PD.

Evaluation of galectin-3 and titin in cats with a sarcomeric gene mutation associated with echocardiography

Background and Aim: Cardiac biomarkers, such as serum galectin-3 (Gal-3) and titin levels, may be related to cats with sarcomeric gene mutations. This study evaluated cardiac biomarkers and echocardiographic parameters in cats with or without myosin-binding protein C3 (MYBPC3) gene mutations. Materials and Methods: Forty-two healthy cats without cardiac symptoms, including Bengal, Maine Coon, Scottish fold, and Ragdoll cats, were enrolled in this study. Cats were categorized into three groups: Homozygous wild type (n = 17), homozygous MYBPC3 gene mutation (n = 14), and heterozygous MYBPC3 gene mutation (n = 11). All recruited cats underwent echocardiography, and blood samples were collected for DNA extraction. DNA sequencing for MYBPC3 gene mutations at A31P and A74T loci was first examined by Sanger sequencing. The biomarkers of cardiac fibrosis (Gal-3) and myocardial stiffness (titin) were measured by enzyme-linked immunosorbent assay. Results: Gal-3 levels &gt;250 pg/mL were associated with echocardiographic parameters. However, Gal-3 levels were not significantly different between cats with MYBPC3 gene mutations and those in the wild-type group. Titin was associated with the left ventricular (LV) thickness and systolic function (r = 0.405, p = 0.013). Qualitative measurement of titin antibodies showed that the highest percentage of these antibodies was found in homozygous wild-type cats. No correlation was found between titin levels and MYBPC3 gene mutations. Weight was positively associated with interventricular septum (r = 0.312, p = 0.056) and LV wall thickness (LVPW) (r = 0.219, p = 0.187). However, they were not associated with Gal-3 levels. Conclusion: LVPW was correlated with weight in cats with sarcomeric gene mutations. Serum titin may be an underlying factor for cardiac hypertrophy in cats. Keywords: cardiac biomarker, cat, hypertrophic cardiomyopathy, myosin-binding protein C3.

The content of soluble forms of galectins -1, -3, -4, -7, -9 in patients with renal cell cancer of various morphological types

Background: Galectins are a family of β-galactoside binding proteins that regulate the vast majority of cellular functions, including proliferation, migration, adhesion, and phagocytosis in both health and disease. More and more experimental and clinical evidence indicates that galectins are involved in many stages of carcinogenesis, including patients with renal cell carcinoma (RCC). Aim: To analyze the clinical significance of soluble forms of galectins -1, -3, -4, -7, -9 in patients with various histological RCC types. Materials and methods: We performed a retrospective analysis of the clinical significance of galectins -1, -3, -4, -7, -9 in the serum of 140 RCC patients (84 with clear cell RCC (ccRCC), 38 with papillary (papRCC), 18 with chromophobe (chrRCC)) and in 73 healthy donors (control group), who were examined and treated from 2019 to 2023 in the N. N. Blokhin National Medical Research Center of Oncology. Galectin levels were measured in serum (obtained according to standard methods before the initiation of specific treatment) with an enzyme-linked immunosorbent assay. Results: There was a significant increase in serum galectin -1, -3, -9 levels in the whole RCC patient group, compared to the healthy donor control group; no increase was found for galectins -4 and -7. Serum galectin-1 levels in the ccRCC and papRCC patients were significantly higher than those in the controls (p = 0.0003 and p = 0.0135, respectively). No association between the serum galectins -1 and -7 and the clinical and morphological characteristics of RCC was found; however, serum galectin-7 levels in the papRCC patients correlated with the grade of tumor differentiation (r = -0.592; p = 0.001). The area under the ROC curve (AUC) for galectin-1 in ccRCC was 0.721 (p 0.0001), in papRCC 0.673 (p = 0.0086), and in chrRCC 0.576 (p = 0.355). For galectin-7, the ROC AUC values were 0.527 (p = 0.634) in ccRCC, 0.513 (p = 0.845) in papRCC, and 0.566 (p = 0.425) in chrRCC. In all histological types of RCC, there was a significant increase in serum galectin-3 compared to the controls (ccRCC, p = 0.0208; papRCC, p = 0.0014; chrRCC, p = 0.0041). The ROC analysis for galectin-3 in patients with RCC of various histological types showed AUC = 0.721 (p 0.0001) for ccRCC, 0.673 (p = 0.0086) for papRCC, and 0.576 (p = 0.355) for chrRCC. Galectin-9 levels was directly and significantly associated with the tumor size, as well as with regional metastases (r = 0.251, p = 0.021; r = 0.239, p = 0.028, respectively). The AUC values for galectin-4 were 0.619 (p = 0.021) in ccRCC, 0.577 (p = 0.214) in papRCC, and 0.534 (p = 0.666) for chrRCC. For galectin-9, they were 0.649 (p = 0.0075), 0.613 (p = 0.087), and 0.539 (p = 0.637), respectively. Conclusion: The study has demonstrated a certain association between serum galectin -1, -3, -4, -7, and -9 in the patients with RCC of various histological types. Although the results of the ROC analysis indicated average quality of the model, which does not allow for the use of the obtained data for diagnostic purposes, it is necessary to continue the research for better understanding of the mechanisms of galectin functioning, before galectin-based therapeutic agents would be introduced into clinical practice for the treatment of RCC.

Targeting Galectin-1 Overcomes Paclitaxel Resistance in Esophageal Squamous Cell Carcinoma.

Resistance to paclitaxel poses a major obstacle in esophageal squamous cell carcinoma (ESCC) treatment. A better understanding of the mechanisms underlying paclitaxel resistance could help identify prognostic biomarkers and improved therapeutic strategies. In this study, we established a patient-derived xenograft (PDX) model of acquired paclitaxel resistance and used RNA-sequencing to identify galectin-1, encoded by LGALS1, as a key mediator of resistance. Integrative analysis of clinical data and physiological studies indicated that serum galectin-1 levels were elevated in resistant patients and correlated with treatment outcomes before and during taxane therapy. Importantly, exposing cells to serum from resistant patients resulted in increased paclitaxel resistance compared to serum from sensitive patients, which was closely associated with galectin-1 concentrations in the serum. The specific clearance of galectin-1 from resistant patient serum significantly restored paclitaxel sensitivity, and inhibiting galectin-1, through knockdown or the pharmacologic inhibitor OTX008, increased sensitivity to paclitaxel. Galectin-1 inhibition reduced the activity of β-catenin, thereby inhibiting stem cell properties induced by the Wnt/β-catenin pathway. Furthermore, galectin-1 regulated MDR1 transcription through increased nuclear accumulation of β-catenin, thus increasing resistance to paclitaxel. Combining OTX008 with clinical taxane formulations effectively reversed paclitaxel resistance in vitro and in vivo. Elevated galectin-1 levels thus serve as an indicator of response to paclitaxel therapy in ESCC, offering a therapeutic intervention strategy to overcome drug resistance.

Serum Galectin-10: A biomarker for persistent airflow limitation in adult asthmatics

BackgroundInhaled corticosteroids (ICS) are primary anti-inflammatory medications to control eosinophilic airway inflammation, and prevent asthma exacerbation. However, persistent airflow limitation (PAL) presents in some asthmatics even on ICS treatment, leading to lung function decline. Thus, we evaluated clinical associations of serum galectin-10 (Gal10) and galectin-3 (Gal3) levels in adult asthmatics who had maintained anti-asthma medication. MethodsSixty-seven asthmatics and 78 healthy controls (HCs) were recruited. Serum Gal10 and Gal3 levels were measured by enzyme-linked immunosorbent assay, and their clinical relevance with inflammatory and lung function parameters was evaluated. Spirometry was performed to assess PAL and small airway dysfunction (SAD). Airway epithelial cells were cocultured with eosinophils/neutrophils, and were exposed to house dust mites to assess the production of Gal10 and Gal3. ResultsSerum Gal10 (not Gal3) levels were significantly higher in asthmatics than in HCs (P < 0.001), in asthmatics with PAL than in those without PAL (P = 0.005), and in those with SAD than in those without SAD (P = 0.004). The Gal10-high group had significantly higher levels of peripheral CD66+ neutrophil counts, serum periostin and Gal3, and lower values of FEV1% and MMEF% than the Gal10-low group (P < 0.050 for all). The production of Gal10 and Gal3 was increased in eosinophilic airway model, while Gal10 (not Gal3) levels were increased in neutrophilic airway model as well as house dust mite stimulation. ConclusionOur findings suggest that serum Gal10 level may be a potential biomarker for PAL in adult asthmatics.

Assessment of Galectin 3 as a New Biomarker of Liver Fibrosis in Chronic HCV Egyptian Patients and its Correlation to Transient Elastography, FIB-4 Index, and APRI Score

Abstract Background Invasive liver biopsy is the current method for the assessment of liver fibrosis. In search of noninvasive alternatives, galectin-3-binding protein (G3BP) was introduced as a candidate-marker of hepatitis C-related fibrosis based on serum proteomics. Aim of the Work to evaluate serum Galectin-3 as a marker of liver fibrosis and correlate it to the stage of fibrosis assessed by FibroScan, FIB-4 index and APRI score Patients and Methods This was prospective study, was carried out on 30 patients with liver fibrosis/cirrhosis due to chronic HCV inthe Hepatic Virology Unit and the gastroenterology department of Ain Shams university hospitals and 30 health controls with normal, non fibrotic and non cirrhotic, liver, from January 2022 to June 2022 Results There were high significant difference between both groups as regard Serum level of Galectin-3 and APRI score. Conclusion Serum level of galectin-3 was highly expressed in chronic HCV Egyptain patients and positively correlated to FIB-4 index, APRI score and fibroscan.so the serum level of galectin-3 beside other modalities, lab investigations and clinical examination may guide us about the progression to fibrosis and cirrhosis in those patients. In these patients, if galectin-3 levels were found to be high, serum alpha-feto protein level and ultrasonographic examination could be repeated at more frequent intervals. This may also guide us in terms of the treatment plan. Measurement of galectin-3 in sera of large number of patients and follow up may pave the way to pick up early fibrosis and showed its prognostic effect.

Effects of Luhong Yixin Granules on myocardial fibrosis in heart failure rats based on TGF-β1/Smads signaling pathway

To investigate the effects of Luhong Yixin Granules on myocardial fibrosis in rats with heart failure and its possible mechanism, a total of 60 male Wistar rats were randomly divided into the control group, model group, and low-, medium-and high-dose Luhong Yixin Granules groups, with 12 rats in each group. Except for those in the control group, rats in the other groups were induced by intraperitoneal injection of doxorubicin(DOX) into a rat model. After the Luhong Yixin Granules were dissolved in the same amount of normal saline, they were given by gavage at low, medium and high doses(2.8, 5.6, 11.2 g·kg~(-1)·d~(-1)), and the control group and the model group were given the same amount of normal saline by gavage for 40 days. After the end of dosing, echocardiography was used to measure left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS). Rat body weight(BW) and heart weight(HW) were calculated as HW/BW. Enzyme-linked immunosorbent assay was used to measure the levels of interleukin-6(IL-6), interleukin-17(IL-17), tumor necrosis factor-α(TNF-α), transforming growth factor-β1(TGF-β1), growth stimulation expressed gene 2 protein(ST2), N-terminal pro-B-type natriuretic peptide(NT-proBNP), galectin-3(Gal-3) and creatine kinase isoenzyme(CK-MB) in serum. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of myocardial tissue. Western blot and quantitative real-time polymerase chain reaction were used to detect the protein and mRNA expression levels of IL-6, IL-17, TNF-α, TGF-β1, Smad3, Smad7, α-smooth muscle actin(α-SMA), and collagen Ⅰ(COL-Ⅰ), respectively. RESULTS:: showed that compared with those in the control group, LVEF, LVFS, and HW/BW in the model group were decreased(P&lt;0.05), and the levels of IL-6, IL-17, TNF-α, TGF-β1, ST2, NT-proBNP, Gal-3, and CK-MB were increased(P&lt;0.05). HE staining showed inflammatory changes in myocardial tissue; Masson staining showed decreases in the cross-sectional area and ventricular cavity area of the heart, and myocardial fibrosis of varying degrees(P&lt;0.05). The protein and mRNA expression of IL-6, IL-17, TNF-α, TGF-β1, Smad3, α-SMA, and COL-Ⅰ were increased(P&lt;0.05), and the protein and mRNA expression of Smad7 protein was decreased(P&lt;0.01). Compared with those in the model group, LVEF, LVFS and HW/BW of the low-, medium-and high-dose Luhong Yixin Granules groups were increased(P&lt;0.05), and the levels of IL-6, IL-17, TNF-α, TGF-β1, ST2, NT-proBNP, Gal-3 and CK-MB were decreased(P&lt;0.05). HE staining showed gradually reduced inflammatory changes of myocardial tissue, and Masson staining showed increased cross-sectional area and ventricular cavity area of the heart and decreased area of myocardial fibrosis(P&lt;0.05). The protein and mRNA expression levels of IL-6, IL-17, TNF-α, TGF-β1, Smad3, α-SMA, and COL-Ⅰ were decreased(P&lt;0.05), while the protein and mRNA expression levels of Smad7 were increased(P&lt;0.05). Luhong Yixin Granules may be of great value in the treatment of heart failure by regulating the TGF-β1/Smads signaling pathway, inhibiting the expression of inflammation-related proteins, reducing the deposition of extracellular matrix, and alleviating myocardial fibrosis.

Prognostic Value of Serum Galectin-3 for Survival in Patients with Cardiac Light-Chain Amyloidosis.

Amyloid light-chain (AL) amyloidosis is a multisystem disorder, with cardiac amyloid infiltration being a prevalent manifestation. This study aimed to explore the prognostic value of galectin-3 (Gal-3), a soluble marker associated with fibrosis, inflammation, heart failure, and kidney injury, in patients with cardiac AL amyloidosis. A total of 60 patients who were diagnosed with cardiac AL amyloidosis from January 2015 to May 2018 were enrolled. The prognostic value of Gal-3 was assessed. Receiver operating characteristic (ROC) curves were used to evaluate the predictive accuracy of Gal-3. A Gal-3 cut-off value was identified to predict survival rates. The ROC curves demonstrated a moderate predictive accuracy of Gal-3 for 0.5- and 5-year survival, with area under the curve (AUC) values of 0.722 and 0.788, respectively. A Gal-3 cut-off value of 15.154 ng/mL was found to predict survival. Kaplan-Meier survival analysis revealed a significant difference in mean overall survival between patients with Gal-3 levels below and above the established cut-off (69.2 months versus 42.1 months, respectively; p = 0.036). Multivariate analysis confirmed that Gal-3 > 15.154 ng/mL remained an independent predictor of survival (HR 2.451, 95% CI 1.017-5.910, p = 0.046). This study suggests that Gal-3 holds independent prognostic value for survival in patients with cardiac AL amyloidosis. Gal-3 could potentially enhance the prognostic capabilities of the current soluble markers, thereby improving the management of cardiac AL amyloidosis. However, further validation in larger prospective studies is warranted.

Correlation Analysis of Genetic Mutations and Galectin Levels in Breast Cancer Patients.

Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients' sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test (α=0.05). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis.

The Role of Galectin-3 Levels for Predicting Paroxysmal Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source.

Background/Objectives: Paroxysmal atrial fibrillation (PAF) is an important cause that is thought main potential factor in Embolic stroke of undetermined source (ESUS). Extended Holter ECG is an expensive and time-consuming examination. It needs another tools for predicting PAF in ESUS patients. In this study, serum galectin-3 levels, ECG parameters (PR interval, P wave time and P wave peak time) LA volume index, LA global peak strain and atrial electromechanical conduction time values were investigated for predicting PAF. Methods: 150 patients with ESUS and 30 volunteers for the control group were recruited to study. 48-72 h Holter ECG monitoring was used for detecting PAF. Patients were divided into two groups (ESUS + PAF and ESUS-PAF) according to the development of PAF in Holter ECG monitoring. Results: 30 patients with ESUS whose Holter ECG monitoring showed PAF, were recruited to the ESUS + PAF group. Other 120 patients with ESUS were recruited to the ESUS-PAF group. PA lateral, PA septum, and PA tricuspid were higher in the ESUS + PAF group (p < 0.001 for all). Serum galectin-3 levels were significantly higher in ESUS + PAF than in ESUS-PAF and control groups (479.0 pg/mL ± 435.8 pg/mL, 297.8 pg/mL ± 280.3 pg/mL, and 125.4 ± 87.0 pg/mL, p < 0.001, respectively). Serum galectin-3 levels were significantly correlated with LAVI, PA lateral, and global peak LA strain (r = 0.246, p = 0.001, p = 0.158, p = 0.035, r = -0.176, p = 0.018, respectively). Conclusion: Serum galectin-3 levels is found higher in ESUS patients which developed PAF and Serum galectin-3 levels are associated LA adverse remodeling in patients with ESUS.

Association between serum galectin-3 and chronic obstructive pulmonary disease: A meta-analysis.

Chronic obstructive pulmonary disease (COPD) is a significant public health issue characterized by progressive and irreversible airflow limitation. The aim of this meta-analysis was to determine the association between changes in serum galectin-3 levels and COPD and to assess the relationship between serum galectin-3 levels and acute exacerbations of COPD (AECOPD). Relevant observational studies were retrieved from electronic databases, including PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI). A random-effects model was used to combine the data, incorporating the influence of between-study heterogeneity. Twelve case-control studies were included. The pooled results showed a significantly higher serum level of galectin-3 in patients with COPD compared to controls (standardized mean difference [SMD] 0.60; 95% confidence interval [CI] 0.40 - 0.80; P < 0.001; I2 = 68%). Further meta-analysis suggested higher levels of serum galectin-3 in patients with AECOPD compared to those with stable COPD (SMD 0.33; 95% CI 0.20 - 0.46; P < 0.001; I2 = 0%). Subgroup analyses according to the mean age of the participants, the proportion of males, and study quality scores did not significantly change the results (P for subgroup differences all > 0.05). In conclusion, patients with COPD were found to have higher serum levels of galectin-3, with levels further elevated in patients with AECOPD compared to those with stable COPD.

Serum Galectin-3 as a Non-Invasive Marker for Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a serious liver disease associated with inflammatory bowel disease (IBD). Galectin-3, an inflammatory and fibrotic molecule, has elevated circulating levels in patients with chronic liver disease and inflammatory bowel disease (IBD). This study aims to clarify whether galectin-3 can differentiate between patients with IBD, PSC, and PSC-IBD. Our study measured serum galectin-3 levels in 38 healthy controls, 55 patients with IBD, and 22 patients with PSC (11 patients had underlying IBD and 11 patients did not), alongside the urinary galectin-3 of these patients and 18 controls. Serum and urinary galectin-3 levels in IBD patients were comparable to those in controls. Among IBD patients, those with high fecal calprotectin, indicating severe disease, exhibited lower serum and elevated urinary galectin-3 levels compared to those with low calprotectin levels. Serum galectin-3 levels were inversely correlated with C-reactive protein levels. PSC patients displayed higher serum and urinary galectin-3 levels than IBD patients, with the highest serum levels observed in PSC patients with coexisting IBD. There was no correlation between serum and urinary galectin-3 levels and laboratory indicators of liver injury in both IBD and PSC patients. In conclusion, this study demonstrates that serum and urinary galectin-3 levels can distinguish IBD from PSC patients, and also reveals higher serum galectin-3 levels in PSC-IBD patients compared to those with isolated PSC.

Serum Mac-2 binding protein glycosylation isomer and galectin-3 levels in adult-onset Still's disease and their association with cytokines.

Autoinflammation with cytokine dysregulation may be implicated in the pathophysiology of adult-onset Still's disease (AOSD); however, the relationship between galectins and cytokines in patients with active AOSD remains unknown. We aimed to examine the relationship between circulating cytokines/chemokines and galectin-3 (Gal-3) or its ligand, Mac-2 binding protein glycosylation isomer (M2BPGi), in Japanese patients with AOSD. We recruited 44 consecutive patients diagnosed with AOSD according to the Yamaguchi criteria, 50 patients with rheumatoid arthritis (RA) as disease controls, and 27 healthy participants. Serum M2BPGi levels were directly measured using a HISCL M2BPGi reagent kit and an automatic immunoanalyzer (HISCL-5000). Serum Gal-3 concentrations were measured by enzyme-linked immunosorbent assay. The serum levels of 69 cytokines were analyzed in patients with AOSD using a multi-suspension cytokine array. We performed a cluster analysis of each cytokine expressed in patients with AOSD to identify specific molecular networks. Significant increases in the serum concentrations of Gal-3 and M2BPGi were found in the serum of patients with AOSD compared with patients with RA and healthy participants (both p <0.001). There were significant positive correlations between serum Gal-3 levels and AOSD disease activity score (Pouchot score, r=0.66, p <0.001) and serum ferritin levels. However, no significant correlations were observed between serum M2BPGi levels and AOSD disease activity scores (Pouchot score, r = 0.32, p = 0.06) or serum ferritin levels. Furthermore, significant correlations were observed between the serum levels of Gal-3 and various inflammatory cytokines, including interleukin-18, in patients with AOSD. Immunosuppressive treatment in patients with AOSD significantly reduced serum Gal-3 and M2BPGi levels (p = 0.03 and 0.004, respectively). Although both Gal-3 and M2BPGi were elevated in patients with AOSD, only Gal-3 was a useful biomarker for predicting disease activity in AOSD. Our findings suggest that circulating Gal-3 reflects the inflammatory component of AOSD, which corresponds to proinflammatory cytokine induction through inflammasome activation cascades.

Accumulation of Microvascular Target Organ Damage in Systemic Lupus Erythematosus Patients Is Associated with Increased Cardiovascular Risk.

Background: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease associated with increased cardiovascular (CV) burden. Besides increased arterial stiffness and subclinical atherosclerosis, microvascular dysfunction is considered an important component in the pathophysiology of CV disease. However, there is a lack of data regarding the effect of multiple target organ damage (TOD) on CV health. Objectives: This study aimed to evaluate (i) the presence of microvascular changes in SLE in various vascular beds, (ii) the possible associations between the accumulation of microvascular TOD and CV risk and (iii) whether Galectin-3 represents a predictor of combined microvascular TOD. Methods: Participants underwent (i) evaluation of skin microvascular perfusion (laser speckle contrast analysis), (ii) fundoscopy (non-mydriatic fundus camera), (iii) indirect assessment of myocardial perfusion (subendocardial viability ratio) and (iv) determination of urine albumin-to-creatinine ratio (UACR). CV risk was calculated using the QResearch Risk Estimator version 3 (QRISK3). Serum Galectin-3 levels were determined. Results: Forty-seven SLE patients and fifty controls were studied. SLE patients demonstrated impaired skin microvascular reactivity (160.2 ± 41.0 vs. 203.6 ± 40.1%), retinal arteriolar narrowing (88.1 ± 11.1 vs. 94.6 ± 13.5 μm) and higher UACR levels compared to controls. Furthermore, SLE individuals had significantly higher Galectin-3 levels [21.5(6.1) vs. 6.6(6.6) ng/dL], QRISK3 scores [7.0(8.6) vs. 1.3(3.6)%] and a greater chance for microvascular dysfunction. In the SLE group, patients with multiple TOD exhibited higher QRISK3. In the multivariate analysis, the accumulation of TOD correlated with disease activity and Galectin-3 (p < 0.05). Conclusions: Our study showed for the first time that SLE patients exhibit a greater number of cases of TOD. The accumulation of TOD was associated with increased CV risk. Clinicians dealing with SLE should be aware and seek microvascular alterations.