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Cancer Progression Mediated by CAFs Relating to HCC and Identification of Genetic Characteristics Influencing Prognosis.
Song, Li; Li, Qiankun; Lu, Yao; Feng, Xianqi; Yang, Rungong; Wang, Shouguo.
Afiliação
  • Song L; Academy of Advanced Interdisciplinary Studies, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province 250353, China.
  • Li Q; Department of Tissue Repair and Regeneration, The First Medical Center of Chinese PLA General Hospital, Beijing, Beijing 250353, China.
  • Lu Y; Department of Tissue Repair and Regeneration, The First Medical Center of Chinese PLA General Hospital, Beijing, Beijing 250353, China.
  • Feng X; Academy of Advanced Interdisciplinary Studies, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province 250353, China.
  • Yang R; Department of Tissue Repair and Regeneration, The First Medical Center of Chinese PLA General Hospital, Beijing, Beijing 250353, China.
  • Wang S; Academy of Advanced Interdisciplinary Studies, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province 250353, China.
J Oncol ; 2022: 2495361, 2022.
Article em En | MEDLINE | ID: mdl-36299502
ABSTRACT

Background:

Hepatocellular carcinoma (HCC) is one of the most common malignancies, and although there are several treatment options, the overall results are not satisfactory. Cancer-associated fibroblasts (CAFs) can promote cancer progression through various mechanisms.

Methods:

HCC-associated mRNA data were sourced from The Cancer Genome Atlas database (TCGA) and International Cancer Genome Consortium (ICGC) database. First, the differentially expressed CAF-related genes (CAF-DEGs) were acquired by difference analysis and weighted gene coexpression network analysis (WGCNA). Moreover, a CAF-related risk model was built by Cox analysis. Kaplan-Meier (K-M) curves and receiver operating characteristic (ROC) curves were utilized to evaluate the validity of this risk model. Furthermore, enrichment analysis of differentially expressed genes (DEGs) between the high- and low-risk groups was executed to explore the functions relevant to the risk model. Furthermore, this study compared the differences in immune infiltration, immunotherapy, and drug sensitivity between the high- and low-risk groups. Finally, we verified the mRNA expression levels of selected prognostic genes by quantitative real-time polymerase chain reaction (qRT-PCR).

Results:

107 CAF-DEGs were identified in the HCC samples, and five prognosis-related genes (ACTA2, IGJ, CTHRC1, CXCL12, and LAMB1) were obtained by Cox analysis and utilized to build a CAF-related risk model. K-M analysis illustrated a low survival in the high-risk group, and ROC curves revealed that the risk model could accurately predict the 1-, 3-, and 5-year overall survival (OS) of HCC patients. In addition, Cox analysis demonstrated that the risk score was an independent prognostic factor. Enrichment analysis illustrated that DEGs between the high- and low-risk groups were related to immune response, amino acid metabolism, and fatty acid metabolism. Furthermore, risk scores were correlated with the tumor microenvironment, CAF scores, and TIDE scores, and CAF-related marker genes were positively correlated with all five model genes. Notably, the risk model was relevant to the sensitivity of chemotherapy drugs. Finally, the results of qRT-PCR demonstrated that the expression levels of 5 model genes were in accordance with the analysis.

Conclusion:

A CAF-related risk model based on ACTA2, IGJ, CTHRC1, CXCL12, and LAMB1 was built and could be utilized to predict the prognosis and treatment of HCC.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Prognostic_studies Idioma: En Revista: J Oncol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Prognostic_studies Idioma: En Revista: J Oncol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China