Interferon-Stimulated Exonuclease Gene 20 is A Prognosis and Predictive Biomarker and Correlated with Macrophages M2 Polarization in Glioblastoma: A Pan-Cancer Analysis

Background: Since the mutation of isocitrate dehydrogenase 1 was confirmed to be different in the tumor microenvironment of multiple cancer types, several researchers have included it in the study of tumor-infiltrating immune cells. Interferon-stimulated exonuclease gene 20 (ISG20) plays a role in the modulation of immunity and inflammation, and its abnormally high expression is conducive for the progression of tumor malignancy. However, whether ISG20 is associated with isocitrate dehydrogenase 1 mutation during tumorigenesis and cancer progression remains unknown to date. Methods: TIMER2.0, ONCOMINE, GEPIA2, TCGA and CGGA were applied to assess the clinical significance of ISG20 and its correlation with tumor-infiltrating immune cells in glioma. cBioPortal and MethSurv databases were used to observe the genetic and DNA methylation changes of ISG20, respectively. Visualization of data was mostly achieved by R language. Quantitative real-time PCR (qRT-PCR) and Immunohistochemistry (IHC) was performed to evaluate the mRNA and protein expression.Results: ISG20 expression was significantly different in most cancers. However, when we combined ISG20 with isocitrate dehydrogenase 1 mutation, we found significant differences only in glioblastoma (GBM). The clinical values of ISG20 in glioblastoma showed that the ISG20 overexpression was strongly associated with a worse overall survival (OS). Additionally, ISG20 was altered in 9% of samples of patients with GBM, and ISG20 expression was negatively correlated with its DNA methylation level. More importantly, ISG20 expression was associated with macrophage alternatively activated (M2) polarization in glioblastoma. Conclusions: ISG20 overexpression is conducive to malignant phenotype but adverse to OS, suggesting that ISG20 is a potential therapeutic target and prognosis and predictive biomarker in patients with GBM.

Isocitrate Dehydrogenase–Mutated Cholangiocarcinoma: Natural History and Clinical Outcomes

Purpose Clinical-pathologic features and natural history of patients with isocitrate dehydrogenase ( IDH)-mutant intrahepatic cholangiocarcinoma (CCA) are not well characterized. Here, we sought to describe the natural history, clinical phenotype, and prognostic impact of advanced, IDH-mutated CCA. METHODS We conducted a multicentric, retrospective analysis of patients with IDH-mutated (IDH1 or IDH2) CCA between 2010 and 2020. Median overall survival (OS) and progression-free survival (PFS) analyses were performed using the Kaplan-Meier method. Chi-square test was used to analyze disease control rate (DCR) and overall response rate (ORR). Matched controls were used for comparing survival between patients with and without IDH mutations (mIDH). RESULTS Sixty-five patients with IDH-mutated CCA were included. All patients had intrahepatic CCA. On first-line chemotherapy, median OS and median PFS were 21.2 months and 8.3 months, respectively. Notably, median OS (32.4 v 19.5 months, P = .12) and PFS (18.0 v 8.0 months, P = .12) were not significantly affected by disease status at presentation (locally advanced v metastatic, respectively). Median OS was significantly longer in patients with mIDH (21.2 v 10.5 months; P < .01). First-line gemcitabine-containing regimens had a significantly higher DCR and ORR than non–gemcitabine-containing regimens (DCR: 75% v 33%, P = .01; ORR: 39% v 0%, P = .02). In patients receiving IDH inhibitor therapy, median PFS was 4.6 months with a DCR of 29%. CONCLUSION CCA with m IDH confers a unique subtype resulting in a better survival compared with that of counterparts. IDH inhibitors represent a promising therapeutic option in later lines of therapy in this subgroup.

Enhanced Production of Citric Acid by Mutant PN12 of Aspergillus fumigatus Using Statistical Design

Distillery spent wash is an unwanted residual liquid waste generated during alcohol production. It is a potential source for production of different industrially important products. Distillery spent wash is dark colored and has many organic compounds as a waste. In this experiment, removal of color and organic compounds was carried out by anaerobic treatment. The treated spent wash was utilized for citric acid production with the help of microorganisms. The current study was performed with the treated spent wash which was applied for high level of citric acid production by a mutant strain of Aspergillus fumigatus PN12. The parent strain Aspergillus fumigatus PN12 was mutagenized by UV exposure to enhance citric acid production. After UV exposure investigation, mutant strain was selected for optimization and statistical method. The best citric acid production obtained was, 26.45 g/L at 30 ℃ with pH 6.0, 0.1 g/L of KH2PO4 and (NH4)2SO4 under OFAT. Under RSM optimization, maximum citric acid production was achieved as 30.89 g/L. Thus, the process optimization through the statistical approach resulted in a 1.16-fold enhancement in citric acid production as compared to that of the OFAT parametric conditions. Citric acid producing enzymes such as aconitase, NAD+-isocitrate dehydrogenase and NADP+ isocitrate dehydrogenase was studied. Maximum activity (U/mg) of aconitase (3.19±0.023), NAD+-isocitrate dehydrogenase (3.0±0.15) and NADP+ isocitrate dehydrogenase (2.91±0.17) was observed at 96 h. The present study can conclude that spent wash is potential source for citric acid production. Utilization of mutant strain of Aspergillus fumigatus PN12 is beneficiary for large scale industrial fermentation and citric acid production.