scholarly journals Identification and Characterization of Copy Number-Associated Driver Genes in Esophageal Squamous Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Kexin Jiang ◽  
Yijiang He ◽  
Xu Zhang
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Copy Number ◽  
Molecular Mechanisms ◽  
Driver Genes ◽  
Oncogenic Pathways

Background. Esophageal squamous cell carcinoma (ESCC) is a leading malignancy with both high incidence and mortality worldwide. However, the molecular mechanisms of the poor prognosis in ESCC are still unclear. Methods. We conducted differential expression analysis between ESCC and normal tissues and between ESCC samples with and without CNAs in a given gene. Overrepresentation enrichment and gene set enrichment analyses were used to identify the oncogenic pathways and abnormal transcription factors (TFs). The survival analysis was employed to identify the genes associated with overall survival. Results. In this study, we aimed to identify and interpret the driver genes triggered by the copy number alterations (CNAs), including CCND1, TEAD4, EIF4EBP1, EGFR, FGFR3, and FZD6. Furthermore, we identified oncogenic pathways, including RTK-RAS, WNT, PI3K, Hippo, and cell cycle, and key TFs including TEAD4, a transcription factor in the Hippo signaling pathway, and LEF1 in the WNT signaling pathway. Furthermore, we observed that upregulations of FGFR3 and EIF4EBP1 were significantly associated with shorter overall survival in ESCC. Conclusion. In conclusion, the driver genes triggered by CNAs not only exhibited critical functionality but also were clinically relevant in ESCC, which greatly improved our understanding of the molecular mechanisms in ESCC.

659 AN SINGLE-ARM OPEN-LABEL PHASE II STUDY OF CAMRELIZUMAB PLUS APATINIB AS SECOND-LINE TREATMENT FOR ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Feng Wang ◽  
Qingxia Fan ◽  
Junsheng Wang ◽  
Tao Wu ◽  
Yonggui Hong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Squamous Cell ◽  
Objective Response ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line

Abstract   Esophageal squamous cell carcinoma (ESCC) as a common malignancy is prevalent in East Asia and in eastern and southern Africa. Although pembrolizumab, nivolumab and camrelizumab are respectively recommended as second-line treatment for advanced ESCC due to improved overall survival (OS), objective response rate (ORR) was modest. New effective treatments are needed. Hence, the study of camrelizumab plus apatinib (VEGFR2 inhibitor) as second-line treatment for advanced ESCC was performed. Methods This ongoing phase II trial (NCT03736863) in six sites in China enrolled pts aged 18-75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line chemotherapy, and an ECOG performance status of 0-1. Pts received 200 mg camrelizumab intravenously every 2 weeks and apatinib 250 mg orally once per day in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and OS. Results At data cutoff (Feb 28, 2021), 52 pts were enrolled, including 42 males and 50 with distant metastases, with the median age of 62 years. In the evaluable population of 39 pts, ORR without confirmation was 43.59% and DCR was 94.87%. The median duration of response was 6.9 months (95% CI 4.57–9.23). The median PFS was 6.8 month (95% CI 2.66–10.94). The 12-month overall survival was 52.2%. A total of 80.8% of pts had treatment-related AEs (TRAEs) with 46.2% of grade ≥ 3 TRAEs. The safety profile of camrelizumab and apatinib was consistent with other anti–PD-1 antibodies and angiogenesis inhibitors. Conclusion This is the first study that evaluates the combination anti–PD-1 antibody and anti-angiogenesis inhibitor as a second-line therapy for advanced ESCC. Camrelizumab plus apatinib showed encouraging clinical efficacy and acceptable safety. Further phase III randomized trials are warranted.

scholarly journals Elevated Maspin Expression Is Associated with Better Overall Survival in Esophageal Squamous Cell Carcinoma (ESCC)

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e63581 ◽  
Author(s):  
Yang Wang ◽  
Shijie Sheng ◽  
Jianzhi Zhang ◽  
Sijana Dzinic ◽  
Shaolei Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Maspin Expression

scholarly journals Involvement of Indoleamine 2,3-Dioxygenase in Impairing Tumor-Infiltrating CD8+T-Cell Functions in Esophageal Squamous Cell Carcinoma

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Ge Zhang ◽  
Wan-Li Liu ◽  
Lin Zhang ◽  
Jun-Ye Wang ◽  
Miao-Huan Kuang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Survival Time ◽  
Squamous Cell ◽  
Tumor Immune Escape ◽  
Cell Functions ◽  
Indoleamine 2,3 Dioxygenase ◽  
Overall Survival Time

The indoleamine 2,3-dioxygenase-(IDO-) mediated microenvironment plays an important role in tumor immune escape. However, the inhibitory effects of IDO on the CD8+tumour-infiltrating lymphocytes (CD8+TILs) in esophageal squamous cell carcinoma (ESCC) have not been clarified yet. Here, we found that the level of IDO expression in ESCC tumor specimens correlated with a reduction in the number of CD8+TILs. Patients with high IDO expression and a low number of CD8+TILs had significantly impaired overall survival time. IDO expression and functional enzyme activity in ESCC cell lines could be induced by IFNγ. When exposed to the milieu generated by IDO-expressing Eca109 cells, the CD8+TILs were suppressed in proliferation, and their cytolytic functions against target tumor cells were lost. These results suggested that impairing CD8+TIL functions by IDO expressed in ESCC possibly contributed to the finding that patients with higher IDO expression have more aggressive disease progression and shorter overall survival time.

scholarly journals LINC00261 Suppresses Cisplatin Resistance of Esophageal Squamous Cell Carcinoma Through miR-545-3p/MT1M Axis

2021 ◽  
Vol 9 ◽  
Author(s):  
Lijun Wang ◽  
Xiaojun Wang ◽  
Pengwei Yan ◽  
Yatian Liu ◽  
Xuesong Jiang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Cure Rate ◽  
Downstream Target ◽  
Downstream Target Gene ◽  
Non Coding Rnas ◽  
New Treatment

To improve the survival rate and cure rate of patients, it is necessary to find a new treatment scheme according to the molecular composition of (ESCC) in esophageal squamous cell carcinoma. Long non-coding RNAs (lncRNAs) regulate the progression of ESCC by various pathophysiological pathways. We explored the possible function of the lncRNA LINC00261 (LINC00261) on cisplatin (DDP) resistance of ESCC and its relative molecular mechanisms. In the study, we found that LINC00261 was downregulated in ESCC tissues, cell lines, and DDP-resistant ESCC patients. Besides, overexpression of LINC00261 not only inhibited cell proliferation, and DDP resistance but also promotes cell apoptosis. Further mechanistic research showed that LINC00261 sponged miR-545-3p which was negatively correlated with the expression of LINC00261. In addition, functional experiments revealed that upregulation of miR-766-5p promoted proliferation and enhanced DDP resistance. Subsequently, MT1M was testified to be the downstream target gene of miR-545-3p. Rescue experiments revealed that overexpression of MT1M largely restores miR-545-3p mimics-mediated function on ESCC progression. Our results demonstrate that the LINC00261 suppressed the DDP resistance of ESCC through miR-545-3p/MT1M axis.

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