scholarly journals Metabolomic Characterization Reveals ILF2 and ILF3 Affected Metabolic Adaptions in Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Bin Zang ◽  
Wen Wang ◽  
Yiqian Wang ◽  
Pengfei Li ◽  
Tian Xia ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Acid Metabolism ◽  
Metabolic Reprogramming ◽  
Chain Acyl ◽  
Glycolysis Pathway ◽  
Cancer Tissues

Esophageal cancer (EC) is a common malignant disease in eastern countries. However, a study of the metabolomic characteristics associated with other biological factors in esophageal squamous cell carcinoma (ESCC) is limited. Interleukin enhancer binding factor 2 (ILF2) and ILF3, double-stranded RNA-binding proteins, have been reported to contribute to the occurrence and development of various types of malignancy. Nevertheless, the underlying functions of ILF2 and ILF3 in ESCC metabolic reprogramming have never been reported. This study aimed to contribute to the metabolic characterization of ESCC and to investigate the metabolomic alterations associated with ILF2 and ILF3 in ESCC tissues. Here, we identified 112 differential metabolites, which were mainly enriched in phosphatidylcholine biosynthesis, fatty acid metabolism, and amino acid metabolism pathways, based on liquid chromatography–mass spectrometry and capillary electrophoresis–mass spectrometry approaches using ESCC tissues and paired para-cancer tissues from twenty-eight ESCC patients. In addition, ILF2 and ILF3 expression were significantly elevated in EC tissues compared to the histologically normal samples, and closely associated with PI3K/AKT and MAPK signaling pathways in ESCC. Moreover, in ESCC tissues with a high ILF2 expression, several short-chain acyl-carnitines (C3:0, C4:0, and C5:0) related to the BCAA metabolic pathway and long-chain acyl-carnitines (C14:0, C16:0, C16:0-OH, and C18:0) involved in the oxidation of fatty acids were obviously upregulated. Additionally, a series of intermediate metabolites involved in the glycolysis pathway, including G6P/F6P, F1,6BP, DHAP, G3P, and 2,3BPG, were remarkably downregulated in highly ILF3-expressed ESCC tissues compared with the corresponding para-cancer tissues. Overall, these findings may provide evidence for the roles of ILF2 and ILF3 during the process of ESCC metabolic alterations, and new insights into the development of early diagnosis and treatment for ESCC. Further investigation is needed to clarify the underlying mechanism of ILF2 and ILF3 on acyl-carnitines and the glycolysis pathway, respectively.

scholarly journals Analysis of SEPT9 Gene Promoter Methylation Status in Esophageal Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Aida Mirza Aghasi ◽  
Saied Ghorbian
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Promoter Methylation ◽  
Methylation Status ◽  
Gene Promoter ◽  
Sodium Metabisulfite ◽  
Significant Difference ◽  
Cancer Tissues

Introduction: The changes in the level of SEPT9 gene promoter methylation can contribute to the formation of esophageal squamous cell carcinoma. The aim of this study was to evaluate the level of changes in the level of SEPT9 gene promoter methylation in the esophageal squamous cell carcinoma. Methods: In the present case-control study, we collected 75 paraffin blocks of esophageal cancer tissues and 75 paraffin blocks healthy tissues, which were referred to the Noor-E-Nejat and Tabriz International Hospitals during 2013-2017. After DNA extraction and treatment with sodium metabisulfite, the changes of SEPT9 gene promoter methylation assessed using high resolution melting (HRM) technique. The data were analyzed by SPSS 22 and Chi-square test. Results: Our findings did not show a statistically significant difference between the changes of SEPT9 gene promoter methylation in cancer tissues compared to the healthy tissues (P=0.106). Conclusion: This study shows that SEPT9 gene promoter methylation cannot contribute to the esophageal squamous cell carcinoma cancerogenesis.  

scholarly journals NRF2/ACSS2 axis mediates the metabolic effect of alcohol drinking on esophageal squamous cell carcinoma

2020 ◽  
Vol 477 (16) ◽  
pp. 3075-3089
Author(s):  
Joab Otieno Odera ◽  
Zhaohui Xiong ◽  
Caizhi Huang ◽  
Ning Gu ◽  
Wenjun Yang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Alcohol Drinking ◽  
Molecular Mechanisms ◽  
Ethanol Exposure ◽  
Metabolic Effect ◽  
Metabolic Reprogramming ◽  
Acetyl Coa

Alcohol drinking is a leading risk factor for the development of esophageal squamous cell carcinoma (ESCC). However, the molecular mechanisms of alcohol-associated ESCC remain poorly understood. One of the most commonly mutated genes in ESCC is nuclear factor erythroid 2 like 2 (NFE2L2 or NRF2), which is a critical transcription factor regulating oxidative stress response and drug detoxification. When NRF2 is hyperactive in cancer cells, however, it leads to metabolic reprogramming, cell proliferation, chemoradioresistance, and poor prognosis. In this study, hyperactive NRF2 was found to up-regulate acetyl-CoA synthetase short-chain family members 2 (ACSS2), an enzyme that converts acetate to acetyl-CoA, in ESCC cells and mouse esophagus. We also showed that knockdown of NRF2 or ACSS2 led to decreased ACSS2 expression, which in turn reduced the levels of acetyl-CoA and ATP with or without ethanol exposure. In addition, ethanol exposure enhanced lipid synthesis in ESCC cells. Moreover, we observed a change in the metabolic profile of ESCC cells exposed to ethanol as a result of their NRF2 or ACSS2 status. We further showed that ACSS2 contributed to the invasive capability of NRF2high ESCC cells exposed to ethanol. In conclusion, the NRF2/ACSS2 axis mediates the metabolic effect of alcohol drinking on ESCC.

PD1+ tumor associated macrophages predict poor prognosis of locally advanced esophageal squamous cell carcinoma

2019 ◽  
Vol 15 (35) ◽  
pp. 4019-4030 ◽  
Author(s):  
Yufei Lu ◽  
Leiming Guo ◽  
Gaofeng Ding
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Locally Advanced ◽  
Rt Pcr ◽  
Tumor Associated Macrophages ◽  
Cancer Tissues

Aim: Tumor associated macrophages are the most abundant cancer immune cells. However, little was known about the identity of CD68+PD1+ macrophages as well as the contributions in the prognosis of esophageal squamous cell carcinoma (ESCC). Methods & methods: Immunofluorescence, flowcytometry and RT-PCR were used to analysis PD1+ macrophages in ESCC. Results: CD68+PD1+ macrophages which can express higher M2 markers in cancer tissues, increased about 4.2-times compared with para-cancer tissues. Additionally, PD1high macrophages were significantly correlated with more malignant phenotypes and poor prognosis. PD1 treatment can enhance phagocytosis of cultured macrophages and redirect this macrophage to M1-like phenotype. Conclusion: Thus, our findings overall indicate that CD68+PD1+ macrophages are tumor associated macrophagess in ESCC, which can forecast the prognosis of ESCC.

scholarly journals Fibroblast activating protein-α expression in squamous cell carcinoma of the esophagus in primary and irradiated tumors: the use of archival FFPE material for molecular techniques

2017 ◽  
Author(s):  
Renata Tabola ◽  
Magdalena Zaremba-Czogalla ◽  
Dagmara Baczynska ◽  
Roberto Cirocchi ◽  
Kamila Stach ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Techniques ◽  
Matched Pair ◽  
Carcinoma Of The Esophagus ◽  
Gene And Protein Expression ◽  
Cancer Tissues

There are numerous reports suggesting that fibroblast activating protein-α (FAP-α) plays an important role in invasion of various tumor types. We studied the expression pattern of FAP-α in esophageal squamous cell carcinoma (ESCC) patients who had not been treated primarily and those who had received neoadjuvant radiochemotherapy. Our goal was to establish whether readily available tissue specimens fixed in formalin and stored in paraffin blocks for years might still be a source of FAP-α RNA for PCR analysis. The study included 20 patients divided into two groups, 10 patients in each group. We evaluated the expression of FAP-α by PCR techniques in fresh frozen and in paraffin-embedded tissues, and compared it to the expression in non-cancer tissues. To detect the protein expression level of FAP-α in paraffin-embedded tissues we used chromogenic immunohistochemical (IHC) staining. Data were analyzed by t-test or the nonparametric Wilcoxon matched pair test using Statistica 12.5 software. We observed an increased level of the FAP-alpha gene and protein expression in cancer tissues when compared with their corresponding normal tissues. However, statistically significant differences were found only in the group of patients untreated before surgery. RNA extracted from paraffin-embedded tissue sections had very low quality, especially in the context of degradation. FAP-α remains a highly altered participant of a complex microenvironment in esophageal squamous cell carcinoma, and its role in cell signaling requires further study. In this paper, we conclude that the use of a regular RT-PCR method for diagnostic purposes, which we have presented in an earlier paper, can be as good as qRT-PCR. Also, immunohistochemistry proved to be very useful and the only reliable method that can be used on formalin-fixed, paraffin-embedded tissues stored long term.

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