scholarly journals WITHDRAWN: Potential therapeutic targets screening for esophageal squamous cell carcinoma via combined analysis of genomic sequencing data and target pharmacophore database

Oncotarget ◽  
2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Ling Zhang ◽  
Ling Zhang ◽  
Feng Liu ◽  
Feng Liu ◽  
Yanghui Bi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Targets ◽  
Genomic Sequencing ◽  
Sequencing Data ◽  
Combined Analysis

scholarly journals Prognostic Value of Combined Analysis of CTLA-4 and PLR in Esophageal Squamous Cell Carcinoma (ESCC) Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Cui-Ying Zhang ◽  
Juan Zhang ◽  
Yun-Fan Ma ◽  
Hong Zhe ◽  
Ren Zhao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Value ◽  
Cytotoxic T Lymphocyte ◽  
Expression Level ◽  
Prognostic Role ◽  
Combined Analysis

Objective. The purpose of this study was to evaluate the prognostic role of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) expression level and the platelet lymphocyte ratio (PLR) level in esophageal squamous cell carcinoma (ESCC) patients. Methods. 84 ESCC patients who received surgical treatment in our hospital were enrolled in the study. The correlation of each biomarker’s level with ESCC patients’ clinicopathological characteristics and overall survival (OS) was assessed. Results. The elevated expression rate of T-CTLA-4 (tumor cell CTLA-4) and I-CTLA-4 (interstitial lymphocyte CTLA-4) was 48.8% and 44.0%, respectively. The number of enrolled patients with a higher PLR level (≥119) was 48. The prognostic value of T-CTLA-4, I-CTLA-4, and PLR in ESCC patients was not detected. However, patients with both a low T-CTLA-4 expression level and a low PLR level that had longer OS (p=0.023) were found. The prognostic role of T-CTLA-4(-) +PLR (-) status in ESCC patients was also confirmed in multivariate analyses (p=0.027). Conclusion. These results demonstrated the potential prognostic value of combined analysis of CTLA-4 and PLR in ESCC patients.

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 A Computational Systems Analyses to Identify Biomarkers and Mechanistic Link in Psoriasis and Cutaneous Squamous Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Sidra Adil ◽  
Rehan Zafar Paracha ◽  
Salma Tariq ◽  
Maryum Nisar ◽  
Sadaf Ijaz ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Targets ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Sequencing Data ◽  
Skin Cancers ◽  
Autoimmune Pathology ◽  
Significant Pathway ◽  
Potential Biomarkers

Psoriasis is the most common and chronic skin disease that affects individuals from every age group. The rate of psoriasis is increasing over the time in both developed and developing countries. Studies have revealed the possibility of association of psoriasis with skin cancers, particularly non-melanoma skin cancers (NMSC), which, include basal cell carcinoma and cutaneous squamous cell carcinoma (cSCC). There is a need to analyze the disease at molecular level to propose potential biomarkers and therapeutic targets in comparison to cSCC. Therefore, the second analyzed disease of this study is cSCC. It is the second most common prevalent skin cancer all over the world with the potential to metastasize and recur. There is an urge to validate the proposed biomarkers and discover new potential biomarkers as well. In order to achieve the goals and objectives of the study, microarray and RNA-sequencing data analyses were performed followed by network analysis. Afterwards, quantitative systems biology was implemented to analyze the results at a holistic level. The aim was to predict the molecular patterns that can lead psoriasis to cancer. The current study proposed potential biomarkers and therapeutic targets for psoriasis and cSCC. IL-17 signaling pathway is also identified as significant pathway in both diseases. Moreover, the current study proposed that autoimmune pathology, neutrophil recruitment, and immunity to extracellular pathogens are sensitive towards MAPKs (MAPK13 and MAPK14) and genes for AP-1 (FOSL1 and FOS). Therefore, these genes should be further studied in gene knock down based studies as they may play significant role in leading psoriasis towards cancer.

scholarly journals Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma

2012 ◽  
Vol 5 (1) ◽  
pp. 73 ◽  
Author(s):  
Wusheng Yan ◽  
Joanna H Shih ◽  
Jaime Rodriguez-Canales ◽  
Michael A Tangrea ◽  
Kris Ylaya ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Targets

scholarly journals Fusobacterium Nucleatum Predicts a Risk for Esophageal Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Chao Shi ◽  
Zhen Li ◽  
Jiawen Zheng ◽  
Weimin Kong ◽  
Taibing Fan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Clinical Stage ◽  
Fusobacterium Nucleatum ◽  
Protein Domain ◽  
Major Type ◽  
Neoplastic Progression ◽  
Sequencing Data

Abstract Background: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in China. The role of the bacteria present in Esophageal squamous cell carcinoma (ESCC) tissue in neoplastic progression has not been fully elucidated. This study aimed to uncover different bacterial communities in ESCC tissues and examine the correlation between the abundance of the esophageal flora and clinical characteristics of ESCC.Method: Samples from total of 111 ESCC patients were collected, and 21 pairs of ESCC samples were analyzed by 16S rRNA sequencing. qPCR was used to verify the abundances of specific bacteria. Gene Ontology and protein domain analyses were used to analyze the whole-exome sequencing data of ESCC specimens to analyze the relationship between the abundance of the esophageal flora and signaling pathways.Results: Microorganisms in tumors and normal tissues showed obvious clustering characteristics. The abundance of Fusobacterium (P=0.0052) was increased in tumor tissues. The high level of Fusobacterium nucleatum was significantly associated with pT stage (P=0.039) and clinical stage (P=0.0039). The WES data showed that COL22A1, TRBV10-1, CSMD3, SCN7A and PSG11 were present in only the F. nucleatum-positive ESCC samples. GO and protein domain enrichment results suggested that epidermal growth factor might be involved in the regulation of cell apoptosis in F. nucleatum-positive ESCC. Both a higher mutational burden and F. nucleatum-positive was observed in tumors with metastasis than in tumors without metastasis.Conclusion: F. nucleatum is closely related to the pT stage and clinical stage of ESCC. The abundance of F. nucleatum and tumor mutation burden may be used in combination as a marker to predict metastasis in ESCC.

scholarly journals Interleukin 32 Promotes Foxp3+ Treg Cell Development and CD8+ T Cell Function in Human Esophageal Squamous Cell Carcinoma Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Li Han ◽  
Shiyu Chen ◽  
Zheyi Chen ◽  
Bingqian Zhou ◽  
Yingxia Zheng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Treg Cells ◽  
Sequencing Data

Proinflammatory cytokine interleukin 32 (IL-32) is involved in infectious diseases and cancer, but what subtypes of immune cells express IL-32 and its roles in tumor microenvironment (TME) have not been well discussed. In this study, we applied bioinformatics to analyze single-cell RNA sequencing data about tumor-infiltrating immune cells from esophageal squamous cell carcinoma (ESCC) TME and analyzed IL-32 expression in different immune cell types. We found CD4+ regulatory T cells (Treg cells) express the highest level of IL-32, while proliferating T and natural killer cells expressed relatively lower levels. Knocking down of IL-32 reduced Foxp3 and interferon gamma (IFNγ) expressions in CD4+ and CD8+ T cells, respectively. IL-32 was positively correlated with Foxp3, IFNG, and GZMB expression but was negatively correlated with proliferation score. IL-32 may have a contradictory role in the TME such as it promotes IFNγ expression in CD8+ T cells, which enhances the antitumor activity, but at the same time induces Foxp3 expression in CD4+ T cells, which suppresses the tumor immune response. Our results demonstrate different roles of IL-32 in Treg cells and CD8+ T cells and suggest that it can potentially be a target for ESCC cancer immunosuppressive therapy.

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