Published online Jan 14, 2020. doi: 10.3748/wjg.v26.i2.134
Peer-review started: September 30, 2019
First decision: November 10, 2019
Revised: November 23, 2019
Accepted: December 7, 2019
Article in press: January 7, 2020
Published online: January 14, 2020
Processing time: 105 Days and 1.8 Hours
Hepatocellular carcinoma (HCC) is a common cancer with a poor prognosis. Previous studies revealed that the tumor microenvironment (TME) plays an important role in HCC progression, recurrence, and metastasis, leading to poor prognosis. However, the effects of genes involved in TME on the prognosis of HCC patients remain unclear. Here, we investigated the HCC microenvironment to identify prognostic genes for HCC.
To identify a robust gene signature associated with the HCC microenvironment to improve prognosis prediction of HCC.
We computed the immune/stromal scores of HCC patients obtained from The Cancer Genome Atlas based on the ESTIMATE algorithm. Additionally, a risk score model was established based on Differentially Expressed Genes (DEGs) between high‐ and low‐immune/stromal score patients.
The risk score model consisting of eight genes was constructed and validated in the HCC patients. The patients were divided into high- or low-risk groups. The genes (Disabled homolog 2, Musculin, C-X-C motif chemokine ligand 8, Galectin 3, B-cell-activating transcription factor, Killer cell lectin like receptor B1, Endoglin and adenomatosis polyposis coli tumor suppressor) involved in our risk score model were considered to be potential immunotherapy targets, and they may provide better performance in combination. Functional enrichment analysis showed that the immune response and T cell receptor signaling pathway represented the major function and pathway, respectively, related to the immune-related genes in the DEGs between high- and low-risk groups. The receiver operating characteristic (ROC) curve analysis confirmed the good potency of the risk score prognostic model. Moreover, we validated the risk score model using the International Cancer Genome Consortium and the Gene Expression Omnibus database. A nomogram was established to predict the overall survival of HCC patients.
The risk score model and the nomogram will benefit HCC patients through personalized immunotherapy.
Core tip: We constructed a risk score model based on hepatocellular carcinoma (HCC) microenvironment that could predict the overall survival (OS) of HCC. It has a high sensitivity and specificity in predicting the OS, and was validated using the Gene Expression Omnibus and the International Cancer Genome Consortium dataset. In addition, the risk score model is associated with immunosuppressive environment and immune checkpoint expression, which will assist clinicians in selecting personalized immunotherapy for HCC patients.