دورية أكاديمية

Identification and clinical validation of EMT-associated prognostic features based on hepatocellular carcinoma

التفاصيل البيبلوغرافية
العنوان: Identification and clinical validation of EMT-associated prognostic features based on hepatocellular carcinoma
المؤلفون: Dafeng Xu, Yu Wang, Jincai Wu, Shixun Lin, Yonghai Chen, Jinfang Zheng
المصدر: Cancer Cell International, Vol 21, Iss 1, Pp 1-21 (2021)
بيانات النشر: BMC, 2021.
سنة النشر: 2021
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
LCC:Cytology
مصطلحات موضوعية: EMT, HCC, Prognosis, G6PD, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
الوصف: Abstract Background The aim of this study was to construct a model based on the prognostic features associated with epithelial–mesenchymal transition (EMT) to explore the various mechanisms and therapeutic strategies available for the treatment of metastasis and invasion by hepatocellular carcinoma (HCC) cells. Methods EMT-associated genes were identified, and their molecular subtypes were determined by consistent clustering analysis. The differentially expressed genes (DEGs) among the molecular subtypes were ascertained using the limma package and they were subjected to functional enrichment analysis. The immune cell scores of the molecular subtypes were evaluated using ESTIMATE, MCPcounter, and GSCA packages of R. A multi-gene prognostic model was constructed using lasso regression, and the immunotherapeutic effects of the model were analyzed using the Imvigor210 cohort. In addition, immunohistochemical analysis was performed on a cohort of HCC tissue to validate gene expression. Results Based on the 59 EMT-associated genes identified, the 365—liver hepatocellular carcinoma (LIHC) samples were divided into two subtypes, C1 and C2. The C1 subtype mostly showed poor prognosis, had higher immune scores compared to the C2 subtype, and showed greater correlation with pathways of tumor progression. A four-gene signature construct was fabricated based on the 1130 DEGs among the subtypes. The construct was highly robust and showed stable predictive efficacy when validated using datasets from different platforms (HCCDB18 and GSE14520). Additionally, compared to currently existing models, our model demonstrated better performance. The results of the immunotherapy cohort showed that patients in the low-risk group have a better immune response, leading to a better patient’s prognosis. Immunohistochemical analysis revealed that the expression levels of the FTCD, PON1, and TMEM45A were significantly over-expressed in 41 normal samples compared to HCC samples, while that of the G6PD was significantly over-expressed in cancerous tissues. Conclusions The four-gene signature construct fabricated based on the EMT-associated genes provides valuable information to further study the pathogenesis and clinical management of HCC.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1475-2867
Relation: https://doaj.org/toc/1475-2867
DOI: 10.1186/s12935-021-02326-8
URL الوصول: https://doaj.org/article/7db4f30d144f4431a78638ec27c454dc
رقم الأكسشن: edsdoj.7db4f30d144f4431a78638ec27c454dc
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14752867
DOI:10.1186/s12935-021-02326-8