scholarly journals Distinct Landscapes of Genetic and Epigenetic Alterations of E2F Family Genes Between Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma

2020 ◽  
Author(s):  
Guo-Liang Zheng ◽  
Guo-Jun Zhang ◽  
Tian-Yi Wu ◽  
Yan Zhao ◽  
Zhi-Chao Zheng
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Esophageal Adenocarcinoma ◽  
Squamous Cell ◽  
Cancer Genomics ◽  
Mrna Levels ◽  
Epigenetic Alterations ◽  
Genetic Changes ◽  
E2f Transcription Factors

Abstract Background/Aims: Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are primarily driven by different genetic changes. The E2F transcription factors (E2Fs) are involved in various malignancies; yet little is known about their roles in ESCC and EAC. This study aimed to investigate genetic and epigenetic alterations of the E2F family genes in ESCC and EAC, and to examine whether the differential changes are associated with the distinct mechanisms. Materials and Methods: mRNA and methylation levels of E2F family genes in ESCC and EAC were retrieved from the database UALCAN. The cBioPortal for Cancer Genomics and Search Tool for the Retrieval of Interacting Genes (STRING) database were used to analyze genetic mutations and interaction networks for E2Fs, respectively.Results: The genetic alteration patterns of E2Fs were different between ESCC and EAC. Furthermore, differences in methylation levels, CNV, and mutation frequency in certain E2F family genes were observed between ESCC and EAC. Moreover, E2Fs were co-expressed and interacted with proteins involved in the N6-methyladenosine (m6A) and histone modifications in EC. Additionally, Kaplan–Meier analysis revealed significant lower E2F1, E2F3, E2F5, E2F7, and E2F8 mRNA levels in association with better prognosis for EAC; while lower E2F1, E2F3, E2F6, E2F7, and E2F8 mRNA levels indicated poorer outcome for ESCC. Conclusions: The different patterns of genetic and epigenetic alterations in the E2F family genes between ESCC and EAC are likely to be associated with different mechanisms. Certain E2Fs hold promise as biomarkers for differential diagnosis of EAC and ESCC, and for prognostic prediction.

scholarly journals Potential Role of Targeting KDR and Proteasome Inhibitors in the Therapy of Esophageal Squamous Cell Carcinoma

2020 ◽  
Vol 19 ◽  
pp. 153303382094806
Author(s):  
Ling Zhang ◽  
Xia Niu ◽  
Yanghui Bi ◽  
Heyang Cui ◽  
Hongyi Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Zinc Finger Protein ◽  
Cancer Genomics ◽  
Therapeutic Targets ◽  
Specific Inhibitor ◽  
Genomic Variation ◽  
Tumor Xenograft

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancer types in China. In recent years, progress has been made in various types of cancer genomics including ESCC. However, the clinical significance of genomic variation of ESCC remains poorly defined. In the present study, genomic sequencing data from 469 ESCC cases were analyzed and potential therapeutic targets in the Druggable Genome Interaction Database (DGIdb) were screened. A series of potential therapeutic target genes and pathways were identified, of which treatment of ESCC with bortezomib (a specific inhibitor targeting proteasome) potently inhibited the proliferation of 5 ESCC cell lines and administration of bortezomib led to significant tumor xenograft regression in SCID mice. It was also identified that kinase insert domain receptor (KDR), which had drug recommendations from all 6 sources integrated by the DGldb and harbored significant amplification in ESCC, might be a downstream target of zinc finger protein 750 (ZNF750). ZNF750 acts as a transcription factor and has been demonstrated to harbor frequently inactivating mutations in ESCC by previous independent studies. In the present study, KDR was upregulated upon ZNF750 knockdown and the rescue of ZNF750 also led to marked restoration of KDR. KDR knockdown in stable ZNF750-knockdown KYSE150 and KYSE140 ESCC cells significantly attenuated the promotion of cell growth, colony formation, invasion and migration induced by ZNF750 knockdown. Further experiments found that apatinib treatment, a potent inhibitor of KDR, resulted in profound inhibition of cell proliferation and invasion. Collectively, the present study provided insight for genomic alterations as potential therapeutic targets in ESCC and supported the possibility of a therapeutic strategy targeting the proteasome in ESCC. The present results also suggested that targeting KDR may be an effective way to treat ESCC, not only in KDR variant cases, but also in individuals with ZNF750 mutations and deletions.

scholarly journals Preliminary evaluation for Bit1 as a potential biomarker for squamous cell carcinoma and adenocarcinoma of esophagus

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770826
Author(s):  
Jing Chen ◽  
Hongtao Liu ◽  
Pan Gao ◽  
Yiran Hui ◽  
Zhenzhen Yang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Matrix Metalloproteinase ◽  
Cell Carcinoma ◽  
Esophageal Adenocarcinoma ◽  
Squamous Cell ◽  
Expression Patterns ◽  
Matrix Metalloproteinase 2 ◽  
Potential Biomarker ◽  
Well Differentiated

Mounting evidence has demonstrated that Bit1 has been investigated as an etiological factor for certain cancers, including esophageal squamous cell carcinoma reported in our previous study, but data regarding possible roles of Bit1 in esophageal squamous cell carcinoma and esophageal adenocarcinoma remain to be elucidated. The purpose of this study was to examine whether Bit1 can be a novel diagnostic marker for the patients with esophageal squamous cell carcinoma and esophageal adenocarcinoma. The results revealed that Bit1 level in esophageal squamous cell carcinoma was significantly higher than that in esophageal adenocarcinoma tissues ( p < 0.05); notably, Bit1 level in esophageal adenocarcinoma tissues was lower than that in paired normal tissues but no difference was found ( p > 0.05). Bit1 expression patterns were completely in accordance with matrix metalloproteinase 2 and Bcl-2 in esophageal squamous cell carcinoma and esophageal adenocarcinoma. In addition, Bit1, Bcl-2, and matrix metalloproteinase 2 expression patterns in different differentiated esophageal squamous cell carcinoma were higher than those in corresponding normal esophageal tissues. Bit1 expression in poorly differentiated esophageal squamous cell carcinoma was significantly higher than that in normal esophageal tissues ( p < 0.05) but not in moderately and well-differentiated esophageal squamous cell carcinoma. Matrix metalloproteinase 2 expression patterns in poorly and moderately differentiated esophageal squamous cell carcinoma were significantly higher than those in corresponding normal esophageal tissues ( p < 0.01) but not in well-differentiated esophageal squamous cell carcinoma tissue ( p > 0.05). Bcl-2 expression patterns in various differentiated esophageal squamous cell carcinoma were higher than those in corresponding normal esophageal tissues with no statistical differences ( p > 0.05). Importantly, Bit1 expression was positively correlated with both matrix metalloproteinase 2 and Bcl-2 expression in esophageal squamous cell carcinoma and esophageal adenocarcinoma tissues ( p < 0.05). Collectively, these preliminary data support further investigation of Bit1 as an important diagnostic factor for esophageal squamous cell carcinoma and esophageal adenocarcinoma.

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