scholarly journals Integrative topological analysis of mass spectrometry data reveals molecular features with clinical relevance in esophageal squamous cell carcinoma

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
She-Gan Gao ◽  
Rui-Min Liu ◽  
Yun-Gang Zhao ◽  
Pei Wang ◽  
Douglas G. Ward ◽  
...  
2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Shirui Chen ◽  
Kai Zhou ◽  
Liguang Yang ◽  
Guohui Ding ◽  
Hong Li

The incidence and histological type of esophageal cancer are highly variable depending on geographic location and race/ethnicity. Here we want to determine if racial difference exists in the molecular features of esophageal cancer. We firstly confirmed that the incidence rate of esophagus adenocarcinoma (EA) was higher in Whites than in Asians and Blacks, while the incidence of esophageal squamous cell carcinoma (ESCC) was highest in Asians. Then we compared the genome-wide somatic mutations, methylation, and gene expression to identify differential genes by race. The mutation frequencies of some genes in the same pathway showed opposite difference between Asian and White patients, but their functional effects to the pathway may be consistent. The global patterns of methylation and expression were similar, which reflected the common characteristics of ESCC tumors from different populations. A small number of genes had significant differences between Asians and Whites. More interesting, the racial differences of COL11A1 were consistent across multiple molecular levels, with higher mutation frequency, higher methylation, and lower expression in White patients. This indicated that COL11A1 might play important roles in ESCC, especially in White population. Additional studies are needed to further explore their functions in esophageal cancer.


2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Xue-feng Leng ◽  
Wenwu He ◽  
Tianqin Mao ◽  
Yongtao Han

Abstract   Long-term survival in esophageal squamous cell carcinoma (ESCC) is related with pathological response after neoadjuvant chemoradiation therapy (NCRT) followed by surgery. However, effective biomarkers for prediction of pathologic response is still lacking. Therefore, a systematic analysis focusing on genes associated with efficacy of chemoradiotherapy in ESCC will provide valuable insights to understand the molecular features. Methods We collected genes associated with efficacy of chemoradiotherapy by screening publications deposited in PubMed. A specific subnetwork was constructed using Steiner minimum tree algorithm. Then the correlations between gene expression and prognosis of ESCC patients was analyzed using Kaplan–Meier Plotter online resources. The key gene expression was evaluated by quantitative real-time polymerase chain reaction, western blotting analysis and immunohistochemical staining. The predictive performance of biomarkers was estimated using receiver operating characteristic (ROC) curve analysis. Results We identified 101 genes associated with efficacy of chemoradiotherapy. Moreover, specific molecular network included some potential related genes, such as CUL3, MUC13, MMS22L, MME, UBC, VAPA, CYP1B1 and UGDH. MMS22L mRNA expression level had most significant association with the ESCC patient outcome (P < 0.01). Furthermore, MMS22L was downregulated at both the mRNA (P < 0.01) and protein levels in tumor compared with normal tissues. Lymph node metastasis was significantly associated with low MMS22L expression (P < 0.001). MMS22L levels were inversely correlated with NCRT response in ESCC (P < 0.01). MMS22L yielded an area under the ROC curve (AUC) of 0.847 (P < 0.01). Conclusion Low MMS22L expression could be an effective predictive biomarker for resistance to NCRT in ESCC.


2021 ◽  
Vol 8 ◽  
Author(s):  
Bin Zang ◽  
Wen Wang ◽  
Yiqian Wang ◽  
Pengfei Li ◽  
Tian Xia ◽  
...  

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.


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