Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8^(+)T cell immune infiltration and immune suppression.We constructed a CD8^(+)T cells related risk score model to predic...Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8^(+)T cell immune infiltration and immune suppression.We constructed a CD8^(+)T cells related risk score model to predict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8^(+)T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS 2,and TNFRSF1B was constructed.The risk score model was well validated through an independent external validation cohort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P<0.0001)and lower CD8^(+)T cells infiltration(P<0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P<0.01).Drug sensitivity analysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene model was verified by immunohistochemistry.In summary,the establishment and validation of a CD8^(+)T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.展开更多
基金国家自然科学基金项目(No.81902513)山西省应用基础研究计划项目(No.202303021211114 and 202103021224228)山西省高等教育百亿工程“科技引导”专项(No.BYJL047)资助。
文摘Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8^(+)T cell immune infiltration and immune suppression.We constructed a CD8^(+)T cells related risk score model to predict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8^(+)T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS 2,and TNFRSF1B was constructed.The risk score model was well validated through an independent external validation cohort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P<0.0001)and lower CD8^(+)T cells infiltration(P<0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P<0.01).Drug sensitivity analysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene model was verified by immunohistochemistry.In summary,the establishment and validation of a CD8^(+)T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.
