Untargeted metabolomics analysis of esophageal squamous cell cancer progression.

90% of esophageal cancer are esophageal squamous cell carcinoma (ESCC) and ESCC has a very poor prognosis and high mortality. Nevertheless, the key metabolic pathways associated with ESCC progression haven't been revealed yet. Metabolomics has become a new platform for biomarker discovery over recent years. We aim to elucidate dominantly metabolic pathway in all ESCC tumor/node/metastasis (TNM) stages and adjacent cancerous tissues. We collected 60 postoperative esophageal tissues and 15 normal tissues adjacent to the tumor, then performed Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) analyses. The metabolites data was analyzed with metabolites differential and correlational expression heatmap according to stage I vs. con., stage I vs. stage II, stage II vs. stage III, and stage III vs. stage IV respectively. Metabolic pathways were acquired by Kyoto Encyclopedia of Genes and Genomes. (KEGG) pathway database. The metabolic pathway related genes were obtained via Gene Set Enrichment Analysis (GSEA). mRNA expression of ESCC metabolic pathway genes was detected by two public datasets: gene expression data series (GSE)23400 and The Cancer Genome Atlas (TCGA). Receiver operating characteristic curve (ROC) analysis is applied to metabolic pathway genes. 712 metabolites were identified in total. Glycerophospholipid metabolism was significantly distinct in ESCC progression. 16 genes of 77 genes of glycerophospholipid metabolism mRNA expression has differential significance between ESCC and normal controls. Phosphatidylserine synthase 1 (PTDSS1) and Lysophosphatidylcholine Acyltransferase1 (LPCAT1) had a good diagnostic value with Area under the ROC Curve (AUC) > 0.9 using ROC analysis. In this study, we identified glycerophospholipid metabolism was associated with the ESCC tumorigenesis and progression. Glycerophospholipid metabolism could be a potential therapeutic target of ESCC progression.

Peripheral CD4+ T cells correlate with response and survival in patients with advanced non-small cell lung cancer receiving chemo-immunotherapy.

Background: The aim of the present study was to explore the potential of peripheral immune cells in predicting the response and prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving anti-PD-1 immunotherapy and platinum-based chemotherapy. Participants and Methods: We utilized flow cytometry to examine the levels and dynamics of blood immune cells in 79 advanced NSCLC patients treated with the chemoimmunotherapy between December 2019 and January 2022. The pre- and post-treatment blood samples were collected within 3 days prior to the initiation of the first and third cycle of combination treatment, respectively. Progression-free survival (PFS) and overall survival (OS) analyses were conducted using Kaplan-Meier method and Cox regression models. Results: The pre-treatment CD4+/Total T cells ratio was significantly higher in responders than non-responders (P < 0.05). The levels of pre-treatment total lymphocytes (P = 0.012), total B lymphocytes (P = 0.025), and NK cells (P = 0.022), and post-treatment NK cells (P = 0.011) and NKT cells (P = 0.035) were significantly associated with OS. Post-treatment CD8+/Total T cells ratio was positively correlated with OS (P = 0.038). In multivariate analysis, post-treatment NK cells and post-treatment CD4+CD8+/Total T cells ratio were negatively associated with OS (hazard ratio [HR] = 10.30, P = 0.038) and PFS (HR = 1.95, P = 0.022), respectively. Notably, significantly positive correlations were observed between CD4+/Total T cells ratio and prognosis both before and after treatment (P < 0.05). Conclusion: To summarize, our finding reveals that high CD4+/total T cells ratio was associated with favorable response and prognosis, highlighting its potential as a predictive biomarker to guide the selection of likely responders to platinum and anti-PD-1 combination therapy.

Keratin gene signature expression drives epithelial-mesenchymal transition through enhanced TGF-ß signaling pathway activation and correlates with adverse prognosis in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) stands as the foremost histological subtype of non-small-cell lung cancer, accounting for approximately 40% of all lung cancer diagnoses. However, there remains a critical unmet need to enhance the prediction of clinical outcomes and therapy responses in LUAD patients. Keratins (KRTs), serving as the structural components of the intermediate filament cytoskeleton in epithelial cells, play a crucial role in the advancement of tumor progression. This study investigated the prognostic significance of the KRT family gene and developed a KRT gene signature (KGS) for prognostic assessment and treatment guidance in LUAD. Methods: Transcriptome profiles and associated clinical details of LUAD patients were meticulously gathered from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The KGS score was developed based on the expression of five prognostic KRT genes (KRT7, KRT8, KRT17, KRT18, and KRT80), and the upper quartile of the KGS score was chosen as the cutoff. The Kaplan-Meier method was evaluated to compare survival outcomes between KGS-high and KGS-low groups. The underlying mechanism was further investigated by GSEA, GSVA, and other bioinformatic algorithms. Results: High expression of the KGS signature exhibited a robust association with poorer overall survival (OS) in the TCGA-LUAD dataset (HR: 1.81; 95% CI: 1.35-2.42, P = 0.00011). The association was further corroborated in three external GEO cohorts, including GSE31210 (HR: 3.31; 95% CI: 1.7-6.47, P = 0.00017), GSE72094 (HR: 1.95; 95% CI: 1.34-2.85, P = 0.00057) and GSE26939 (HR: 3.19; 95% CI: 1.74-5.84, P < 0.0001). Interestingly, KGS-high tumors revealed enrichments in TGF-ß and WNT-ß catenin signaling pathways, exhibited heightened activation of the epithelial-mesenchymal transition (EMT) pathway and proved intensified tumor stemness compared to their KGS-low counterparts. Additionally, KGS-high tumor cells exhibited increased sensitivity to several targeted agents, including gefitinib, erlotinib, lapatinib, and trametinib, in comparison to KGS-low cells. Conclusion: This study developed a KGS score that independently predicts the prognosis in LUAD. High expression of KGS score, accompanied by upregulation of TGF-ß and WNT-ß catenin signaling pathways, confers more aggressive EMT and tumor progression.

CUL4B is a Potential Novel Prognostic Biomarker and is Correlated with Immune Infiltrates in Malignant Pleural Mesothelioma.

Background: Malignant pleural mesothelioma (MPM) is a particularly fatal cancer with a median survival of less than one year. The value of single-agent checkpoint inhibitors is still obscure in MPM. We aim to reveal CUL4B prognostic role and immune infiltrates in MPM patients. Methods: CUL4B expression profile and clinical information of malignant pleura mesothelioma individuals were collected from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) dataset. Quantitative real-time PCR (qRT-PCR) analysis measured CUL4B mRNA expression in epithelioid, biphasic, sarcomatoid, and normal pleural cell lines. Results: CUL4B expression elevated in MPM and had a high diagnostic value with AUC = 0.772. Additionally, our results showed that CUL4B high expression significantly correlated with poorer outcomes in MPM. Moreover, GSEA revealed 15 KEGG pathways enriched in the CUL4B high-expression group, and 22 were exhibited in the CUL4B low-expression group. Otherwise, our results showed that CUL4B was relevant to Wnt antagonistic factors (BARX2), Insulin-like growth factor binding protein 3 (IGFBP3), and Phosphatase and tensin homolog (PTEN). In addition, our results revealed that CUL4B expression was positively linked with four types of immune cells, whereas CUL4B expression was negatively linked with three types of immune cells. Additionally, our results showed that CUL4B expression regulates T helper cells, Tcm, and Th2 cells infiltration MPM microenvironment. Finally, our results identified CUL4B high expression in MPM cell line NCI-H2052 (epithelioid), MSTO-211H (biphasic), and NCI-H28 (sarcomatoid). Conclusion: CUL4B is a valuable prognostic biomarker and a critical immune cell infiltration regulator in MPM.

Long noncoding RNA GK-IT1 promotes esophageal squamous cell carcinoma by regulating MAPK1 phosphorylation.

BACKGROUND: Long noncoding RNAs (lncRNAs) are implicated in the oncogenesis and metastasis of multiple human cancers. Nonetheless, the precise molecular mechanisms underlying the oncogenic role of lncRNA in esophageal squamous cell carcinoma (ESCC) remains to be clarified. METHODS: The expression of GK intronic transcript 1 (GK-IT1) was analyzed using ESCC RNA-seq data from The Cancer Genome Atlas database. Quantitative real-time PCR was used to measure the expression of GK-IT1 in ESCC clinical samples and cells. The correlation between GK-IT1 expression and clinicopathological variables was examined using chi-squared tests. Kaplan-Meier survival and Cox regression analyses were employed to generate the survival curve and assess the prognostic value of GK-IT1. Functional experiments were utilized to explore the role of GK-IT1 in promoting cell migration, invasion, proliferation, and suppressing apoptosis and autophagy in ESCC. To understand the mechanism, an RNA pulldown assay, RNA immunoprecipitation, agarose gel electrophoresis, immunofluorescence, and co-immunoprecipitation assays were used. RESULTS: In this study we identified an unreported lncRNA, termed GK-IT1 that was aberrantly overexpressed in ESCC tissues and cells. GK-IT1 was closely associated with advanced clinical stage, and it was an independent prognostic indicator of ESCC. Functional assays verified that GK-IT1 significantly promoted ESCC proliferation, invasion, and migration, and suppressed ESCC apoptosis and autophagy. Furthermore, tumorigenesis experiments in nude mice indicated that GK-IT1 promoted ESCC tumor growth and metastasis. Mechanistically, GK-IT1 competitively bound to mitogen-activated protein kinase 1 (MAPK1) to prevent the interaction between dual specificity phosphatase 6 (DUSP6) and MAPK1, thereby controlling the phosphorylation of MAPK1 and promoting ESCC progression. CONCLUSION: Our study revealed that GK-IT1 competed with DUSP6 to attenuate the interaction between DUSP6 and MAPK1, leading to activation of the ERK/MAPK pathway, thereby promoting progression of ESCC. Our research indicated that GK-IT1 served as a novel potential target for the diagnosis and treatment of ESCC.

Microwave-assisted co-pyrolysis of chlorella vulgaris and polypropylene: Characteristic and product distribution analyses.

The co-pyrolysis characteristics and product yield of Chlorella vulgaris (CV) and polypropylene (PP) under different mixing ratios (10:0, 8:2, 6:4, 5:5, 4:6, 2:8 and 0:10) were studied by microwave oven. Then the effects of different graphite (GP) additions (10%, 20%, 30% and 40%) on the optimum mixing ratio of CV and PP were investigated. The composition of bio-oil was analyzed by GC-MS. The results indicated that the C8P2 (CV/PP = 8:2) group had the best pyrolysis characteristics. The maximum weight loss rate (Rm) and average weight loss rate (Rv) of the C8P2 with 30% GP addition achieved the peak value. In the absence of GP, compared with C10P0 group, the contents of nitrogen compounds in bio-oil of the C8P2 group decreased by 21.58%. After adding GP to the C8P2 group, the nitrogen compounds in bio-oil of 30% GP group was 1.93% lower than that in 0% GP group.

Study on microwave pyrolysis and production characteristics of Chlorella vulgaris using different compound additives.

Pyrolysis characteristics and bio-oil of Chlorella vulgaris were investigated under SiC and ZnO (SZ) mixture (compound additive) with various mixing ratios (S/Z = 10:0, 7:3, 5:5, 3:7, 0:10) and addition amounts (5%, 10%, 15%) by thermogravimetric analysis and GC-MS. At three experimental groups of 10% compound additive, as ZnO in compound additive increased, maximum weight loss rate (Rp) increased, the time (tp) corresponding to Rp and the weight stabilization time (tf) first decreased and then increased, while average rate of weight loss (Ra) and total weight loss (M) first increased and then decreased; maximum temperature rising rate (Hx) and average rate of temperature rising (Hg) increased, while the time (tx) corresponding to Hx decreased. Compound additives reduced the bio-oil yield, increased the gas yield, and reduced the acid compounds in bio-oil. Besides, it might promote the production of alicyclic hydrocarbons and oxygen/nitrogen-containing long-chain compounds.