Search

Purpose: The primary objective was to establish whether blood-based leucine-rich alpha-2-glycoprotein (LRG1) can predict outcomes in patients with locally advanced prostate cancer undergoing androgen-deprivation therapy (ADT) and radiotherapy (RT) and to determine how it may relate to 92 immune-oncology (I-O)-related proteins in this setting. Methods: Baseline blood level of LRG1 from patients treated with ADT and RT enrolled in the CuPCa (n = 128) and IMRT (n = 81) studies was measured using ELISA. A longitudinal cohort with matched blood samples from start of ADT, start of RT, and end of RT protocol from 47 patients from the IMRT cohort was used to establish levels of I-O proteins by high-multiplexing Proximal Extension Assay by Olink Proteomics. Statistical analyses using Kaplan–Meier, Cox regression, and LIMMA analyses were applied to predict the prognostic value of LRG1 and its correlation to I-O proteins. Results: High baseline levels of LRG1 predicted a low frequency of treatment failure in patients undergoing ADT + RT in both the CuPCa and the IMRT cohorts. LRG1 was moderately correlated with CD4, IL6, and CSF1. We identified I-O proteins predicting metastatic failure (MF) at different timepoints. Conclusion: LRG1 biomarker is associated with I-O proteins and can be used to improve stratification and monitoring of prostate cancer patients undergoing ADT + RT. This work will require further in-depth analyses in independent cohorts with treatment outcome data. Study outline. A) Study cohorts. B) Sampling time points in a longitudinal cohort. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the diagnostic performance of Leucine-Rich Alpha-2-Glycoprotein (LRG1) in pediatric acute appendicitis (PAA). We conducted a systematic review of the literature in the main databases of medical bibliography. Two independent reviewers selected the articles and extracted relevant data. Methodological quality was assessed using the QUADAS2 index. A synthesis of the results, standardization of the metrics and 4 random-effect meta-analyses were performed. Eight studies with data from 712 participants (305 patients with confirmed diagnosis of PAA and 407 controls) were included in this review. The random-effect meta-analysis of serum LRG1 (PAA vs control) resulted in a significant mean difference (95% CI) of 46.76 μg/mL (29.26–64.26). The random-effect meta-analysis for unadjusted urinary LRG1 (PAA vs control) resulted in a significant mean difference (95% CI) of 0.61 μg/mL (0.30–0.93). The random-effect meta-analysis (PAA vs control) for urinary LRG1 adjusted for urinary creatinine resulted in a significant mean difference (95% CI) of 0.89 g/mol (0.11–1.66). Conlusion: Urinary LRG1 emerges as a potential non-invasive biomarker for the diagnosis of PAA. On the other hand, due to the high between-study heterogeneity, the results on serum LRG1 should be interpreted with caution. The only study that analyzed salivary LRG1 showed promising results. Further prospective studies are needed to confirm these findings. What is Known: • Pediatric acute appendicitis continues to be a pathology with a high rate of diagnostic error. • Invasive tests, although useful, are a source of stress for patients and their parents. What is New: • LRG1 emerges as a promising urinary and salivary biomarker for the noninvasive diagnosis of pediatric acute appendicitis. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a commonly seen severe case in clinical practice and the main cause of health loss worldwide. Objective: We investigated the biological function of LRG1 and its underlying molecular mechanisms in sepsis-renal injury. Mice of sepsis model group were subjected to cecal ligation and puncture (CLP) surgery after anesthetization. THP-1 cell was induced by LPS for vitro model. Results: The mRNA and protein levels of LRG1 in renal tissue of sepsis model were reduced. LRG1 could reduce the inflammation reaction in model of sepsis-renal injury. In addition, LRG1 up-regulation reduced inflammation reaction and ROS production levels in vitro model via the activation of HIF-1α and suppression of NLRP3 inflammasome. Knockout of LRG1 increased inflammation reaction and ROS production levels in vitro model via the inactivation of HIF-1α and induction of NLRP3 inflammasome. Furthermore, the inhibition of HIF-1α reduced the effects of LRG1 on NLRP3 inflammasome in vitro model. Conclusions: The present study suggests that LRG1 expression reduced inflammation of sepsis-renal injury via activation of NLRP3 inflammasome by HIF-1α, thereby may be a promising therapeutic target of sepsis-renal injury. [ABSTRACT FROM AUTHOR]

Background: Leucine-rich alpha-2-glycoprotein-1 (LRG1) is widely involved in proliferation, migration, and invasion of various tumor cells. Recent studies have evaluated the potential of LRG1 as both an early tumor and a prognostic biomarker. Method: The relevant literature from PubMed is reviewed in this article. Results: It has been found that LRG1 mainly acts on the regulatory mechanisms of angiogenesis, epithelial-mesenchymal transition (EMT), and apoptosis by transforming growth factor (TGF-β) signaling pathway as well as affecting the occurrence and development of the tumors. Moreover, with advancement of research, LRG1 regulation pathways which are independent of TGF-β signaling pathway have been gradually revealed in different tumor cells; There are several studies on the biological effects of LRG1 as an inflammatory factor, vascular growth regulator, cell adhesion, and a cell viability influencing factor. In addition, various tumor suppression methods which are based on regulation of LRG1 levels have also shown high potential clinical value. Conclusions: LRG1 are critical for the processes of tumorigenesis, development, and metastasis in various tumors. The present study reviewed the latest research on the achievements of LRG1 in tumor genesis and development. Further, this study also discussed the related molecular mechanisms of various biological functions of LRG1. [ABSTRACT FROM AUTHOR]

Leucine-rich alpha-2-glycoprotein-1 (LRG1) has been shown to compete with apoptosis activating factor-1 (Apaf-1) for binding cytochrome c (Cyt c) and could play a role in inhibition of apoptosis. Employing MCF-7 breast cancer cells, we report that intracellular LRG1 does protect against apoptosis. Thus, cells transfected with the lrg1 gene and expressing higher levels of LRG1 were more resistant to hydrogen peroxide-induced apoptosis than parental cells, while cells in which LRG mRNA was knocked down by short hairpin (sh) RNA-induced degradation were more sensitive. The amount of Cyt c co-immunoprecipitated with Apaf-1 from the cytosol of apoptotic cells was inversely related to the level of LRG1 expression. In lrg1-transfected cells partially-glycosylated LRG1 was found in the cytosol and there was an increase in cytosolic Cyt c in live lrg1-transfected cells relative to parental cells. However, apoptosis was not spontaneously induced because Cyt c was bound to LRG1 and not to Apaf-1. Cyt c was the only detectable protein co-immunoprecipitated with LRG1. Following hydrogen peroxide treatment degradation of LRG1 allowed for induction of apoptosis. We propose that intracellular LRG1 raises the threshold of cytoplasmic Cyt c required to induce apoptosis and, thus, prevents onset of the intrinsic pathway in cells where Cyt c release from mitochondria does not result from committed apoptotic signaling. This mechanism of survival afforded by LRG1 is likely to be distinct from its extracellular survival function that has been reported by several research groups. [ABSTRACT FROM AUTHOR]

Leucine-rich α glycoprotein 1 (LRG1) has been shown to be aberrantly expressed in multiple human malignancies. However, the biological functions of LRG1 in human glioblastoma remain unknown. Here, we report for the first time the role of LRG1 in glioblastoma development based on the preliminary in vitro and in vivo data. We first confirmed the expression of LRG1 in human glioblastoma cell lines. Next, to investigate the role of LRG1 in the tumorigenesis and development of glioblastoma, a short hairpin RNA (shRNA) construct targeting LRG1 mRNA was transfected into U251 glioblastoma cells to generate a cell line with stably silenced LRG1 expression. The results showed that silencing of LRG1 significantly inhibited cell proliferation, induced cell cycle arrest at G0/G1 phase, and enhanced apoptosis in U251 cells in vitro. Consistently, LRG1 silencing resulted in the downregulation of key cell cycle factors including cyclin D1, B, and E and apoptotic gene Bcl-2 while elevated the levels of pro-apoptotic Bax and cleaved caspase-3, as determined by Western blot analysis. We further demonstrate that the silencing of LRG1 expression effectively reduced the tumorigenicity of U251 cells, delayed tumor formation, and promoted apoptosis in a xenograft tumor model in vivo. In conclusion, silencing the expression of LRG1 suppresses the growth of glioblastoma U251 cells in vitro and in vivo, suggesting that LRG1 may play a critical role in glioblastoma development, and it may have potential clinical implications in glioblastoma therapy. [ABSTRACT FROM AUTHOR]

Heart failure is a life-threatening condition that carries a considerable emotional and socio-economic burden. As a result of the global increase in the ageing population, sedentary life-style, increased prevalence of risk factors, and improved survival from cardiovascular events, the incidence of heart failure will continue to rise. Despite the advances in current cardiovascular therapies, many patients are not suitable for or may not benefit from conventional treatments. Thus, more effective therapies are required. Transforming growth factor (TGF) β family of cytokines is involved in heart development and dys-regulated TGFβ signalling is commonly associated with fibrosis, aberrant angiogenesis and accelerated progression into heart failure. Therefore, a potential therapeutic pathway is to modulate TGFβ signalling; however, broad blockage of TGFβ signalling may cause unwanted side effects due to its pivotal role in tissue homeostasis. We found that leucine-rich α-2 glycoprotein 1 (LRG1) promotes blood vessel formation via regulating the context-dependent endothelial TGFβ signalling. This review will focus on the interaction between LRG1 and TGFβ signalling, their involvement in the pathogenesis of heart failure, and the potential for LRG1 to function as a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is one of the most common female malignancies. The patients with high-risk factors may have poor prognosis. Therefore, there is an urgent need to find a new molecule to more accurately predict survival of patients. Leucine-rich-alpha-2-glycoprotein1 (LRG1), one of leucine-rich repeat family, was closely associated with cancer metastasis and poor prognosis. The biological functions and the expression level of LRG1 remain obscure in EC. In this study, by immunohistochemical analysis of 242 EC patient tissues, we found that LRG1 expression was associated with stage and lymphatic metastasis in both test cohort (133 patients) and validation cohort (109 patients). Furthermore, to investigate the prognostic value of LRG1 in endometrial carcinoma, we analyzed the correlation between variables and overall survival with Cox proportional hazard regression. The result showed that LRG1 was an independent prognostic factor for overall survival of endometrial carcinoma patients. To further evaluate the prognostic efficiency of LRG1 in endometrial carcinoma, we compared the sensitivity and specificity of LRG1 in endometrial carcinoma prognosis by logistic regression. The result showed that LRG1 combining with other clinicopathological risk factors was a stronger prognostic model than clinicopathological risk factors alone or their combination. Thus, LRG1 potentially offered clinical value in directing personal treatment for endometrial carcinoma patients. [ABSTRACT FROM AUTHOR]