Erratum: Overexpression of ZEB1 and YAP1 is related to poor prognosis in patients with gliomas with different IDH1 status.

[This corrects the article on p. 138 in vol. 16, PMID: 37559682.].

Overexpression of ZEB1 and YAP1 is related to poor prognosis in patients with gliomas with different IDH1 status.

OBJECTIVE: Whether there is a correlation between zinc-finger E-box-binding homolog 1 (ZEB1) and Yes-associated protein 1 (YAP1) with clinical outcome in gliomas remains unclear. Hence, this study aimed to investigate the effects of ZEB1 and YAP1 on the prognosis of human gliomas and its relationship with the isocitrate dehydrogenase 1 (IDH1) gene state. METHODS: Immunohistochemical staining was used to record the expression levels of ZEB1, YAP1, and p-YAP1 in 122 cases of low-grade glioma (LGGs) and 69 cases of glioblastoma (GBMs). The correlations of ZEB1 and YAP1 with pathological data were determined by Pearson's Chi-square test. Spearman correlation analysis was then used for analyzing the relationship among YAP1, ZEB1, and IDH1 gene status. The effects of ZEB1 and YAP1 on prognosis were investigated through survival analysis. RESULTS: We detected high ZEB1 expression levels in 29 LGGs (23.8%) and 39 GBMs (56.5%), and high YAP1 expression levels in 22 LGGs (18.0%) and 44 of GBM (63.8%). These results revealed that the protein expression levels of ZEB1 and YAP1 were higher in GBM (P < 0.001). There was a significantly positive correlation between ZEB1 and YAP1 (P < 0.001; r = 0.533). High ZEB1 expression was related to tumor grade (P < 0.001) and Ki-67 (P = 0.0037). YAP1 overexpression was correlated with Ki-67 (P < 0.001), P53 (P = 0.009), tumor grade (P < 0.001), and tumor location (P = 0.018). Patients with ZEB1 and YAP1 high expression had worse overall survival (OS) (P < 0.001). The multivariate analysis showed that YAP1 was an independent prognostic factor for OS. In the LGG group, worse OS were observed in glioma patients with elevated YAP1 expression level. Spearman correlation analysis revealed no association between ZEB1 expression and IDH1 state (P = 0.360; r = -0.084), and YAP1 expression had a negative correlation with IDH1 mutation (P < 0.001, r = -0.364). CONCLUSIONS: Our study showed that ZEB1 and YAP1 were significantly activated in GBM, and patients with high ZEB1 and YAP1 expression had worse OS. ZEB1 expression was significantly correlated with YAP1 in glioma. ZEB1 and YAP1 coexpression may serve as a useful prognostic biomarker for glioma, and aberrant YAP1 expression may be associated with IDH1 gene state.

Increased plasma asprosin levels are associated with overeating and loss of control in drug-free bulimia nervosa.

PURPOSE: Abnormalities in appetite hormones have been implicated in bulimia nervosa (BN). Orexigenic hormone asprosin has been reported to be associated with food intake and weight gain, but no relevant studies have yet been reported in BN. This study investigated asprosin concentrations and their association with eating disorder symptoms in patients with BN. METHODS: This study recruited a total of 26 BN patients and 23 healthy controls (HC). Symptom severity for eating disorders, depression, and anxiety was determined by the Eating Disorder Examination Questionnaire 6.0, Beck Depression Inventory, Version 2, and Beck Anxiety Inventory, respectively. In addition, the study employed sandwich enzyme-linked immunoassay technology to determine plasma asprosin and glucose concentrations in all participants. RESULTS: The results revealed that plasma asprosin concentrations were significantly higher in BN patients than in HC (P = 0.037), but the difference disappeared after adjusting for the covariate BMI (F = 2.685, P = 0.108). Correlation analysis showed that asprosin concentration was positively correlated with overeating (r = 0.451, P = 0.021) and eating loss of control (r = 0.483, P = 0.012) in BN patients. Linear regression analysis indicated that an increase in asprosin concentration was associated with an increase in the times of overeating (F = 6.303, P = 0.019, R2 = 0.208). Multiple linear regression showed that increases in asprosin concentration and BDI-II total score could explain the frequent eating loss of control (F = 5.766, P = 0.009, R2 = 0.334). CONCLUSIONS: The present study is the first report of plasma asprosin concentration in BN patients and found that overeating and eating loss of control increased with the increase of asprosin concentration. Additionally, asprosin level and degree of depression may explain the frequency of loss of control. LEVEL OF EVIDENCE: Level III: Evidence obtained from case-control studies.

Analysis of the expression and prognostic value of MT1-MMP, ß1-integrin and YAP1 in glioma.

Increased expression of membrane type 1-matrix metalloproteinase (MT1-MMP/MMP14) is associated with the development of many cancers. MT1-MMP may promote the entry of yes-associated protein1 (YAP1) into the nucleus by regulating the regulation of ß1-integrin. The purpose of this study was to investigate the effects of MT1-MMP, ß1-integrin and YAP1 on the prognosis of gliomas. The expression of proteins was detected by bioinformatics and immunohistochemistry. The relationship between three proteins and clinicopathological parameters was analyzed by the χ 2 test. Survival analysis was used to investigate the effects of three proteins on prognosis. The results showed that high expressions of MT1-MMP, ß1-integrin and YAP1 were found in glioblastoma (GBM) compared with lower-grade glioma (LGG). There was a significantly positive correlation between MT1-MMP and ß1-integrin (r = 0.387), MT1-MMP and YAP1 (r = 0.443), ß1-integrin and YAP1 (r = 0.348). Survival analysis showed that patients with overexpression of MT1-MMP, ß1-integrin and YAP1 had a worse prognosis. YAP1 expression was the independent prognostic factor for progression-free survival (PFS). There was a statistical correlation between the expression of MT1-MMP and YAP1 and isocitrate dehydrogenase 1 (IDHl) mutation. Thus, this study suggested that MT1-MMP, ß1-integrin and YAP1, as tumor suppressors, are expected to be promising prognostic biomarkers and therapeutic targets for glioma patients.

The Expression and Prognostic Value of ILK and YAP1 in Glioma.

Integrin-linked kinase (ILK) is a widely expressed serine/threonine-protein kinase that has been implicated in cancer development, progression, and metastasis. Yes-associated protein (YAP), as the most important effector of Hippo signaling pathway, which is considered to be a tumor suppressor pathway, acts as an oncogene in a variety of human cancers. The present study aimed to explore the expression of ILK and YAP1, the relationship between them, and the effect of ILK, YAP1 on prognosis in gliomas. Immunohistochemistry was used to examine the expression of ILK and YAP1. The χ2 test analyzes the relationship between ILK, YAP1, and pathologic parameters. The Spearman correlation analyzes the relationship between ILK and YAP1. Survival analysis was used to investigate the effect of ILK and YAP1 on prognosis. High expression of ILK was associated with the age above 50 (P=0.003), higher World Health Organization (WHO) grade (P<0.001), recurrence (P<0.001), and Ki-67 expression≥10% (P<0.001). High expression of YAP1 was associated with higher WHO grade (P<0.001), recurrence (P=0.043), and Ki-67 expression ≥10% (P=0.037). In lower grade gliomas, the high expression rate of ILK in isocitrate dehydrogenase 1 wild-type was higher than that in isocitrate dehydrogenase 1 mutant (P=0.048). The high expression rate of YAP1 in 1p19q non-codeletion was higher than that in 1p19q codeletion (P=0.022). There was a positive correlation between ILK and YAP1 (r=0.344). The patients with high expression of ILK and YAP1 had worse OS and PFS. As an upstream factor of the Hippo signaling pathway, ILK may affect the development and prognosis of gliomas by regulating YAP1.

Increased plasma asprosin levels in patients with drug-naive anorexia nervosa.

PURPOSE: Asprosin is a centrally acting appetite-promoting hormone and promotes glucose production in the liver. This study is the first to investigate the difference in asprosin in the plasma between anorexia nervosa (AN) and healthy controls, and to explore the relationship between asprosin changes and plasma glucose levels and AN symptoms. METHODS: Plasma asprosin and glucose concentrations were detected in AN patients (n = 46) and healthy control subjects (n = 47). Eating Disorder Inventory-2 (EDI-2) was used to assess subjects' eating disorder symptoms and related personality traits. The patient's concomitant levels of depression and anxiety were also measured using the beck depression inventory and beck anxiety inventory, respectively. RESULTS: Results indicate that AN patients had a higher asprosin concentration in their plasma compared to healthy controls (p = 0.033). Among AN patients, plasma asprosin levels correlated positively with EDI-2 interoceptive awareness subscale score (p = 0.030) and negatively with duration of illness (p = 0.036). Multiple linear regression analyses showed that increases in asprosin levels (p = 0.029), glucose levels (p = 0.024) and body mass index (p = 0.003) were associated with an increase of the score of EDI-2 bulimia subscale. CONCLUSIONS: Our findings suggest that the increase in plasma asprosin concentration in patients with AN may be a compensation for the body's energy shortage, and asprosin may be involved in the development of bulimia and lack of interoceptive awareness in AN patients. LEVEL OF EVIDENCE: Level III, case-control analytic study.

Expression of YAP1 and pSTAT3-S727 and their prognostic value in glioma.

AIMS: A growing research demonstrated that YAP1 played important roles in gliomagenesis. We explored the expression of YAP1 and STAT3, the relationship between them and the effect of YAP1, STAT3 on prognosis in glioma. METHODS: Expression of YAP1, p-YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 in 141 cases of low-grade gliomas (LGG) and 74 cases of high-grade gliomas (HGG) of surgical specimens were measured by immunohistochemistry. Pearson's X2 test was used to determine the correlation between immunohistochemical expressions and clinicopathological parameters. Pearson's or Spearman correlation test was used to determine the association between these proteins expression. Survival analysis was used to investigate the effect of these proteins on prognosis. RESULTS: High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in HGG compared with LGG (p=0.000). High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in 63.5%, 59.5%, 66.2% and 31.1% cases of HGG, respectively. YAP1 expression was associated to tumour location, Ki-67 and P53, STAT3 expression was related with Ki-67 and P53, and the expression of pSTAT3-S727 was associated with Ki-67. There was a significantly positive correlation between YAP1 and pSTAT3-S727 (p<0.0001; r=0.5663). Survival analysis revealed that patients with YAP1 and pSTAT3-S727 coexpression had worse overall survival (OS) and progression-free survival (PFS) (p<0.0001). Tumour grade, age, Ki-67 and YAP1 expression were independent prognostic factors for OS. In LGG group, both YAP1 and pSTAT3-S727 expressions were negative correlation with IDH1 mutation, YAP1 and pSTAT3-S727 coexpression showed worse OS and PFS of glioma patients. CONCLUSION: Our research showed that YAP1 and STAT3 were significantly activated in HGG compared with LGG. YAP1 significantly correlated with pSTAT3-S727 in glioma, YAP1 and pSTAT3-S727 coexpression may serve as a reliable prognostic biomarker and therapeutic target for glioma.