Ding Huan, Hu Huan, Tian Feifei, Liang Huaping
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
State Key Laboratory of Trauma, Burns and Combined Injury, Department of Wound Infection and Drug, Daping Hospital, Army Medical University, Chongqing 400010, China.
Biosci Rep. 2021 Mar 26;41(3). doi: 10.1042/BSR20204219.
The 5-year survival of hepatocellular carcinoma (HCC) is difficult due to the high recurrence rate and metastasis. Tumor infiltrating immune cells (TICs) and immune-related genes (IRGs) bring hope to improve survival and treatment of HCC patients. However, there are problems in predicting immune signatures and identifying novel therapeutic targets. In the study, the CIBERSORT algorithm was used to evaluate 22 immune cell infiltration patterns in gene expression omnibus (GEO) and the cancer genome atlas (TCGA) data. Eight immune cells were found to have significant infiltration differences between the tumor and normal groups. The CD8+ T cells immune signature was constructed by least absolute shrinkage and selection operator (LASSO) algorithm. The high infiltration level of CD8+ T cells could significantly improve survival of patients. The weighted gene co-expression network analysis (WGCNA) algorithm identified MMP9 was closely related to the overall survival of HCC patients. K-M survival and tROC analysis confirmed that MMP9 had an excellent prognostic prediction. Cox regression showed that a dual immune signature of CD8+ T cells and MMP9 was independent survival factor in HCC. Therefore, a dual prognostic immune signature could improve the survival of patient and may provide a new strategy for the immunotherapy of HCC.
由于高复发率和转移率，肝细胞癌（HCC）的5年生存率较低。肿瘤浸润免疫细胞（TICs）和免疫相关基因（IRGs）为提高HCC患者的生存率和治疗效果带来了希望。然而，在预测免疫特征和识别新的治疗靶点方面存在问题。在本研究中，使用CIBERSORT算法评估基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据中的22种免疫细胞浸润模式。发现肿瘤组和正常组之间有8种免疫细胞存在显著的浸润差异。通过最小绝对收缩和选择算子（LASSO）算法构建了CD8 + T细胞免疫特征。CD8 + T细胞的高浸润水平可显著提高患者的生存率。加权基因共表达网络分析（WGCNA）算法确定基质金属蛋白酶9（MMP9）与HCC患者的总生存期密切相关。K-M生存分析和tROC分析证实MMP9具有出色的预后预测能力。Cox回归显示，CD8 + T细胞和MMP9的双重免疫特征是HCC的独立生存因素。因此，双重预后免疫特征可以提高患者的生存率，并可能为HCC的免疫治疗提供新策略。
