An extracellular matrix-based signature associated with immune microenvironment predicts the prognosis of patients with hepatocellular carcinoma - 28/05/22
, Chenxuan Wu a, b, c, d, ⁎ Highlights |
• | A series of investigations led us to identify 13 ECM-related genes which we utilized to construct a prognostic signature with a larger area under the curve of 0.808. |
• | This ECM-related signature can be utilized as independent predictor of survival in HCC. |
• | Low-risk patients stratified by the final model presented higher sensitivity to 8 targeted drugs (especially sorafenib) and 2 common chemo-drugs. |
• | ECM-associated genes can play a crucial role in tumors development through immune system and that individuals at high risk with HCC can benefit from immunotherapy. |
• | TGF-β pathway act as an important bridge between ECM remodeling procedures and TME of HCC and are worthy of further study. |
• | This signature will assist patients of HCC and give new insights into the underlying processes of the disease. |
Abstract |
Objective |
Increased data showed that genes related to extracellular matrix (ECM) are important to hepatocellular carcinoma (HCC) development. In contrast, no research was carried out that proposed that ECM-related genes should be reliable prognostic signature.
Methods |
This study used data from The Cancer Genome Atlas along with The International Cancer Genome Consortium to gather ECM-related gene expression as well as clinical information related to the extracellular matrix. The least absolute shrinkage, Cox analysis, along with selection operator Cox regression and random forest have been utilized for establishing an ECM-related prognostic models.
Results |
A series of investigations led us to identify 13 ECMs which we utilized to construct a prognostic signature with a larger area under the curve of 0.808. HCC patients have been categorized into 2 main groups based on the risk score formula: low risk along with high risk. The findings of the Kaplan-Meier curve revealed that there had been a statistically significant difference between these two groups. Our ECM-related signature can be utilized as independent predictor of survival in HCC. Low-risk patients stratified by the final model presented higher sensitivity to 8 targeted drugs (especially sorafenib) and 2 common chemo-drugs. Our gene set enrichment analysis outcomes recommended that high-risk group have been enriched in ECM, tumorigenesis, as well as immune-related pathways. Immune cell analysis showed that high-risk group had lower cell fraction of CD8+ T cells, Macrophages M1, B naïve cells, memory resting CD4+ T cells, Monocytes, resting Dendritic cells and activated Mast cells, along with higher PD-1 and CTLA4 expression levels as compared to low-risk group.
Conclusion |
Our identified ECM-related signature can also give new insight into underlying mechanisms along with therapeutic strategies in order to treat HCC.
Il testo completo di questo articolo è disponibile in PDF.Keywords : Hepatocellular carcinoma, Extracellular matrix, CIBERSORT, Prognosis, Tumor microenvironment
Abbreviations : AUC, CTLs, DAVID, ECM, GO, GSEA, ICGC, KEGG, KM, OS, ROC, TCGA, TME, TIDE, TAMs
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Vol 46 - N° 4
Articolo 101877- Aprile 2022 Ritorno al numero
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