IGFBP1 promotes the proliferation and migration of lung adenocarcinoma cells through the PPARα pathway.

BACKGROUND: The immune status is closely linked to cancer progression, metastasis, and prognosis. Lipid metabolism, crucial for reshaping immune status, plays a key role in regulating the advancement of lung adenocarcinoma (LUAD) and deserves further investigation. METHODS: This study classifies LUAD patients into different immune subtypes based on lipid metabolism-related genes and compares the clinical characteristics among these subtypes. Single-multi COX analysis screens out key genes related to prognosis, and a risk feature and prognostic model are constructed. Cell cloning, scratch, transwell, western blotting and flow cytometry cell cycle analysis to detect the function of key genes. A subcutaneous tumor animal model is used to investigate the in vivo function and molecular mechanisms of key genes. RESULTS: LUAD patients are classified into three immune subtypes, among which C3 subtype has lower immune status and higher frequency of gene mutations, and show lower immunoreactivity in immunotherapy. COX analysis identified a prognostic model for four lipid metabolism factors (IGFBP1, NR0B2, PPARA, and POMC). IGFBP1, a core gene in this model, is highly expressed in the C3 subtype. Functionally, knocking down IGFBP1 significantly inhibits tumor cell cloning, scratch, and migration abilities, and downregulates the expression of cell cycle and EMT-related proteins. Knocking down IGFBP1 significantly inhibits tumor burden (P < 0.05). Mechanistically, knocking down IGFBP1 inhibits the activation of PPARα to regulate tumor cell growth. CONCLUSIONS: This study found that lipid metabolism genes are closely related to LUAD, and IGFBP1 may be a key gene in regulating tumor growth and development.

A Nonlinear Relation between Body Mass Index and Long-Term Poststroke Functional Outcome-The Importance of Insulin Resistance, Inflammation, and Insulin-like Growth Factor-Binding Protein-1.

Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.

Protein Plasma Levels of the IGF Signalling System Are Altered in Major Depressive Disorder.

The Insulin-like growth factor 2 (IGF-2) has been recently proven to alleviate depressive-like behaviors in both rats and mice models. However, its potential role as a peripheral biomarker has not been evaluated in depression. To do this, we measured plasma IGF-2 and other members of the IGF family such as Binding Proteins (IGFBP-1, IGFBP-3, IGFBP-5 and IGFBP-7) in a depressed group of patients (n = 51) and in a healthy control group (n = 48). In some of these patients (n = 15), we measured these proteins after a period (19 ± 6 days) of treatment with antidepressants. The Hamilton Depressive Rating Scale (HDRS) and the Self-Assessment Anhedonia Scale (SAAS) were used to measure depression severity and anhedonia, respectively. The general cognition state was assessed by the Mini-Mental State Examination (MMSE) test and memory with the Free and Cued Selective Reminding Test (FCSRT). The levels of both IGF-2 and IGFBP-7 were found to be significantly increased in the depressed group; however, only IGF-2 remained significantly elevated after correction by age and sex. On the other hand, the levels of IGF-2, IGFBP-3 and IGFBP-5 were significantly decreased after treatment, whereas only IGFBP-7 was significantly increased. Therefore, peripheral changes in the IGF family and their response to antidepressants might represent alterations at the brain level in depression.

Serum IGFBP-1 Concentration as a Predictor of Outcome after Ischemic Stroke-A Prospective Observational Study.

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4-8.5 and OR 5.7, 95% CI: 2.5-12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1-3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality.

Study of hydrosalpinx on endometrial growth and expression of HOXA10mRNA and related factors.

Objective: The objective of the study is to extract the patient's endometrium at the time of proliferative stage using hydrosalpinx in order to culture the cells and decidualization induction in vitro. Further, the study is also intended at identifying the expression of HOXA10mRNA and related factors and understand the hydrosalpinx's impact upon the working mechanism of endometrial cells. Methods: Once the extraction of the primary cells is over, the cells are cultured and other activities are performed such as the cell identification, CCK8 assay, cell decidua induction and HE staining. The researchers assessed the expression levels of HOXA10, IGFBP1 and avß3 in either proliferation or secretion of the endometrium. This was accomplished using Western blot assay and real-time fluorescence quantitative PCR. Results: The results confirmed that at the time of endometrial proliferation, there was a decline in the expression of HOXA10 as a result of tubal effusion influence. This affected its expression in the secretory stage i.e., corresponding function. Further, a significant decline was observed in the levels of HOXA10mRNA of endometrial cells that were subjected to continuous tubal effusion, post decidualization. It was found that during decidualization, if thetubal effusion is removed, it is possible to restore the expression of HOXA10mRNA to a certain extent, though it is not possible to reach the general endometrial level. So, in terms of clinical aspects, the expression of HOxa10 mRNA by the endometrial cells decreases significantly when blocking the hydrosalpinx. Conclusions: Among hydrosalpinx patients, one of the major mechanisms that damage the endometrium was found to be the abnormal expression of HOXA10 followed by IGFBP1 and avß3, its downstream genes. This further results in the implantation of the embryo as well. Though it is possible to gradually repair the damage after the removal of hydrosalpinx, the recovery is a time-consuming process.

Association between IGFBP1 expression and cancer risk: A systematic review and meta-analysis.

Background: The results regarding the association between insulin-like growth factor binding protein 1 (IGFBP1) expression and cancer risk were controversial. We performed a meta-analysis to provide novel evidence on relationship between IGFBP1 expression and cancer risk. Methods: PubMed, Embase, Cochrane library and Web of science were searched for relevant cohort and case-control studies exploring the relationship between IGFBP1 expression and cancer risk. Odds ratios (ORs) were pooled in this meta-analysis using random model. Subgroup analyses were performed based on ethnicity, tumor types, publication year, study type, Newcastle-Ottawa Scale (NOS) score and sex. Results: A total of 27 studies including 16 cohort and 11 case-control studies were identified by literature search. No significant association was found between IGFBP1 expression and risk of various cancers [0.90, 95% confidence interval (CI): 0.79, 1.03]. The overall results showed that the pooled ORs were 0.71 (95% CI: 0.57, 0.88] for prostate cancer risk and 0.66 (95%CI: 0.44, 0.99) for colorectal cancer (CRC) risk. However, there is no significant association between IGFBP1 expression and risk for ovarian cancer (1.70, 95%CI: 0.41, 6.99), breast cancer (1.02, 95%CI: 0.85, 1.23), endometrial cancer (1.19, 95%CI: 0.64, 2.21), colorectal adenoma (0.93; 95%CI: 0.81, 1.07), lung cancer (0.81, 95%CI: 0.39, 1.68) or multiple myeloma (1.20, 95%CI: 0.98, 1.47). Conclusion: In this study, compared with individuals at low IGFBP1 expression adjusted for age, smoking status, alcohol intake and so on, risk of the prostate cancer and CRC were decreased among individuals of high IGFBP1 expression. There needs further study to confirm this issue.

Insulin-like growth factor binding protein-1 and insulin in polycystic ovary syndrome: a systematic review and meta-analysis.

Background: Insulin-like growth factor binding protein-1 (IGFBP-1) is considered a decline in polycystic ovary syndrome (PCOS), but it remains controversial that whether such reduction is attributed to obesity. Aims: This systematic review aims to explore whether IGFBP-1 is reduced in PCOS, and whether such reduction is associated with obesity. Results: Our pooled study included 12 studies with a total of 450 participants. IGFBP-1 levels in PCOS were significantly lower than that in non-PCOS (SMD (95%CI)=-0.49(-0.89, -0.09), P=0.02). No significant difference in IGFBP-1 levels between patients with or without PCOS classified by BMI. Whilst, stratification by PCOS status revealed a significant decrease in IGFBP-1 in overweight (SMD (95%CI)=-0.92(-1.46, -0.37), P=0.001). When comparing fasting insulin in the same way, PCOS patients had significantly elevated fasting insulin level but not statistically declined IGFBP-1 after classified by BMI. Conclusion: This meta-analysis provides evidence that the decrease of IGFBP-1 in PCOS was more strongly influenced by comorbid obesity than by PCOS itself. Additionally, contrast to previous findings that insulin significantly suppresses IGFBP-1, our results suggested that the suppression of PCOS-related hyperinsulinemia on IGFBP-1 seemed diminished. Overall, our work may provide a novel perspective on the mechanism between insulin and IGFBP-1 underlying PCOS development.

IGFBP-1 in cancer: expression, molecular mechanisms, and potential clinical implications.

Insulin-like growth factor binding protein-1 (IGFBP-1) belongs to the insulin-like growth factor (IGF) system, which plays an indispensable role in normal growth and development, and in the pathophysiology of various tumors. IGFBP-1 has been shown to be associated with the risk of various tumors, and has a vital function in regulating tumor behaviors such as proliferation, migration, invasion and adhesion through different molecular mechanisms. The biological actions of IGFBP-1 in cancer are found to be related to its phosphorylation state, and the IGF-dependent and -independent mechanisms. In this review, we provided an overview of IGFBP-1 in normal physiology, and its aberrantly expression and the underlying molecular mechanisms in a range of common tumors, as well as discussed the potential clinical implications of IGFBP-1 as diagnostic or prognostic biomarkers in cancer.

[Correlation between automated optical reading and double human reading for two tests of fetal membranes rupture]. / Concordance entre la lecture optique automatisée et la lecture visuelle double pour deux tests de rupture des membranes.

OBJECTIVES: To assess concordance between double human and automated optical reading (AOR) concerning two biological tests for rupture of membranes (ROM) METHODS: We conducted a monocentric, prospective, observational study comparing Actim Prom® (Alere SAS, Jouy-en Josas, France) and Hiprom Duo® (Fumouze, Levallois-Perret, France). Each test was performed simultaneously in patients with suspected ROM and read independently by 2 biologists and AOR device. ROM was clinically confirmed in case of recurrent leakage or spontaneous labour with no perceived membranes within 48hours. RESULTS: Concerning Actim Prom®, concordance was 100 %, 92.5 % and 91.6 % between biologists, biologists-AOR device and biologists or AOR vs. clinical presentation respectively. Concerning Hiprom Duo®, concordance was 97.2 % between biologists, 97.2 % between biologist 1 and AOR, 95.3 % between biologist 2 and AOR, 63.5 % between clinical presentation and human reading, 62.3 % between clinical presentation and AOR. False positive cases were significantly associated with modified cervix (21 % vs. 46 %, P=0.006). CONCLUSION: We demonstrated excellent correlation between biologists and good or excellent correlation between AOR and human reading supporting the use of AOR in clinical practice.

IGFBP1 Involved in the Decreased Birth Weight Due to Fetal High Estrogen Exposure in Mice.

Our previous study indicated that maternal high-estrogen environment in the first trimester is correlated with increased risks of low birth weight (LBW) and adult diseases. The present study aimed to establish an animal model to confirm such an effect in mice, and to further explore the mechanism involved. A mouse model with high estradiol (E2) exposure during early pregnancy was established, and the birth weight, growth after birth, and expression levels of insulin-like growth factor-binding protein 1 (IGFBP1) of pups were examined. Meanwhile, IGFBP1 expression after treatment of E2 was examined in a HepG2 hepatoma cell line. We found that after exposure to a high-E2 environment the weight of the pups decreased significantly, not only before but also after birth. Meanwhile, both mRNA and protein expressions of IGFBP1 were elevated in placenta and liver tissues. Furthermore, the level of IGFBP1 in the HepG2 cell line was elevated by the treatment of E2, whereas this effect was blocked by estrogen receptor antagonist ICI 182780. In summary, maternal high estrogen up-regulates expression of IGFBP1 in placenta and fetal livers, which contributes to LBW and decreases body weight in offspring.

[Comparison of diagnostic performance of two tests of premature rupture of membranes (IGFBP-1/PAMG-1) in clinical practice]. / Comparaison des performances diagnostiques de deux tests de rupture prématurée des membranes (IGFBP-1/PAMG-1) en pratique clinique.

OBJECTIVES: Evaluate the two main immunochromatographic tests of premature rupture of membranes (PROM): Actimprom(®) based on the discovery of insulin-like growth factor binding protein-1 (IGFBP-1) and Amnisure(®) based on the discovery of placental alpha 1-microglobulin (PAMG -1). The comparison was made voluntarily in clinical practice and is interested in a population whose failure is not clean break. MATERIALS AND METHODS: Prospective and comparative study performed on 2012, at the university hospital of Caen, in 85 patients with PROM suspected between 24 SA and 36 SA. The presence of blood, semen or vaginal infection has been notified. Frank rupture of membranes was an exclusion criterion. RESULTS: Actimprom(®) and Amnisure(®) were detected PROM with a specificity, sensitivity, PPV and NPV respectively 89.4% (CI 79.4-95.6%), 68.4% (CI 43.5-87.4%), 65% (CI 40.8-84.6%) and 90.8% (CI 81-96.5%). The results of both tests were not influenced by the presence of blood or inflammatory disease. CONCLUSION: Performance of these tests is probably related to the quality of the sample and the extraction step in bed of the patient. This work showed no significant difference between the two tests in terms of performance in the diagnosis of PROM. At present, there is no formally favor the use of one or the other.