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Expression, prognosis and functional role of Thsd7a in esophageal squamous cell carcinoma of Kazakh patients, Xinjiang.

ABSTRACT: Thsd7a (Thrombospondin type 1 domain containing 7a) is a critical transmembrane protein. Studies have indicated that Thsd7a was associated with cytoskeletal organization, cell migration and filopodia formation. However, the involvement of Thsd7a remains elusive in human Esophageal Squamous Cell Carcinoma (ESCC). Consequently, immunohistochemistry and reverse transcription-polymerase chain reaction were utilized to study the correlation between the expression of Thsd7a and clinical-pathological characteristics. The influence of Thsd7a on apoptosis, cell proliferating activity, cell cycle, migratory and invasive capacity was determined in Eca 109 and EC 9706 cell lines in vitro. And the influence on proliferating activity was testified using naked mice model in vivo. In addition, the potential molecular mechanism was tested by microarray. It was discovered that there is a certain correlation between Thsd7a and the Kazakh ESCC. By knocking out Thsd7a, the invasion, migration and proliferation could be decreased. And it could also arrest the cell cycle at G1 phase and increase the apoptosis rate. It was further verified that Thsd7a had obvious effect on proliferation in naked mice with xenograft of Eca109 cells. Finally, it was uncovered by microarray analysis that a variety of tumor genes and pathways related to Thsd7a. Together, it was demonstrated that Thsd7a might have a certain degree of carcinogenesis in ESCC.

SUBMITTER: Hou Z

PROVIDER: S-EPMC5601160 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Expression, prognosis and functional role of Thsd7a in esophageal squamous cell carcinoma of Kazakh patients, Xinjiang.

Hou Zhichao Z Abudureheman Abulajiang A Wang Lei L Hasim Ayshamgul A Ainiwaer Julaiti J Zhang Haiping H Niyaz Madiniyat M Upur Halmurat H Sheyhidin Ilyar I

Oncotarget 20170408 36

Thsd7a (Thrombospondin type 1 domain containing 7a) is a critical transmembrane protein. Studies have indicated that Thsd7a was associated with cytoskeletal organization, cell migration and filopodia formation. However, the involvement of Thsd7a remains elusive in human Esophageal Squamous Cell Carcinoma (ESCC). Consequently, immunohistochemistry and reverse transcription-polymerase chain reaction were utilized to study the correlation between the expression of Thsd7a and clinical-pathological c ...[more]

PMID: 28947992

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Project description:BackgroundThe role of the PRDM5 in esophageal squamous cell carcinoma (ESCC) has not been revealed. This study investigated the relationship between PRDM5 expression and survival outcome in esophageal squamous cell carcinoma and explored the mechanism in tumor development.MethodsIn present study, expression of PRDM5 mRNA in esophageal squamous cell carcinoma patients was conducted using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The expression of PRDM5 was assessed by immunohistochemical staining. Kaplan-Meier curve and Cox regression analysis was performed to analyze the survival outcome and independent predictive factors. qRT-PCR and Methylation-specific PCR were performed to identify the mRNA level of PRDM5 and Methylation rate. Cibersort algorithm to analyze the relationship between PRDM5 expression and immune cell invasion. Western-blot was performed to confirm the expression of esophageal tumor tissues and adjacent tissues.ResultsThe TCGA database and GEO database show that PRDM5 mRNA level in esophageal squamous cell carcinoma adjacent tissues was higher than that of cancer tissues, and ESCC patients with high expression of PRDM5 mRNA had better overall survival. Tissue microarray showed that the protein level of PRDM5 in the adjacent tissues of patients with ESCC was higher than that in cancer tissues, and the expression level of PRDM5 was significantly correlated with the grade of clinicopathological characteristics (P < 0.001). Patients with high expression of PRDM5 displayed a better OS and DFS. Cox regression analysis showed that PRDM5 was an independent risk factor and prognostic factor for ESCC patients (HR: 2.626, 95%CI: 1.824-3.781; P < 0.001). The protein level of PRDM5 matched with the transcriptional level, whereas the DNA methylation affected the transcriptional level. Cibersort showed that T cells CD4 memory resting, mast cells resting, eosinophils, M2 macrophages and mast cells activated were significantly positively correlated with PRDM5 expression (P < 0.05), while regulatory T cells, monocytes and dendritic cells negatively correlated with PRDM5 expression (P < 0.05).ConclusionPRDM5 can be used as a biomarker to predict the survival of ESCC patients. Furthermore, PRDM5 expression in ESCC cells may affect WNT/β-catenin signaling pathways, thus further affect the ESCC cell proliferation, migration, and invasion capacity.

Dataset Information

Expression, prognosis and functional role of Thsd7a in esophageal squamous cell carcinoma of Kazakh patients, Xinjiang.

Publications

Expression, prognosis and functional role of Thsd7a in esophageal squamous cell carcinoma of Kazakh patients, Xinjiang.

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