Abstract
Background：
The membrane of tumor epithelial cells is more flexible than normal cells, and higher membrane tension can effectively inhibit the migration and invasion of tumor cells. Innovative therapies targeting the physical characteristics of tumor cells are worthy of attention. To investigate the prognostic value of membrane tension-related genes (MTGRs) in hepatocellular carcinoma (HCC) and its relationship with immunotherapy.
Method:
We obtained RNA-seq data and clinical characteristics data for HCC from The Cancer Genome Atlas (TCGA) database, the (International Cancer Genome Consortium) ICGC database and GEO database. Combined with univariate Cox regression analysis and LASSO (least absolute shrinkage and selection operator) regression analyses, 3-MTRGs risk model was established. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve were used to verify the model. The Nomogram model was constructed by combining the risk score and clinical characteristics, and its performance was evaluated by calibration curves. We conducted gene differential analysis and functional enrichment analysis on high- and low-risk groups, identifying relevant molecular pathways. Additionally, we analyzed the differences between the two groups in terms of immune cell infiltration, immune-related pathways, and immunotherapy. In addition, we analyzed single-cell sequencing data of HCC patients from the GEO database to study cellular infiltration in the tumor microenvironment and the distribution of model genes across different cell types. Finally, we validated the expression differences of model genes between HCC tissues and normal tissues using the GEO database (GSE121248 and GSE45267).
Results
3-MTRGs (CFL1, CRTC2, SRGAP2) were involved in the model construction, and the prognosis of patients in the low-risk group was better than that in the high-risk group. Kaplan-Meier survival curve and ROC curve illustrated that the model had reliable predictive value. Enrichment analysis showed that high-risk groups were mainly concentrated in the pathways related to TUMOR CELL CYCLE and ECM RECEPTOR INTERACTION. Immuno-correlation analysis of the two groups showed that the high-risk group was associated with immune escape. High-risk HCC patients exhibited notable sensitivity to chemotherapy drugs such as 5 - Fluorouracil, Dasatinib, Osimertinib and Paclitaxel. External data sets showed that the model genes were highly expressed in HCC tissues.
Conclusion
We selected three MTRGs ( CFL1, CRTC2 and SRGAP2) as prognostic indicators of HCC and established a Nomogram model to predict the prognosis and efficacy of immunotherapy in HCC patients.