Department of Pediatric Surgery, Cangzhou Central Hospital, Xinhua Road, Yunhe District, Cangzhou, Heibei 061000, China.
Cancer Genet. 2021 Jun;254-255:75-81. doi: 10.1016/j.cancergen.2021.02.001. Epub 2021 Feb 10.
Liver cancer is one of the most lethal malignancies, presenting inferior survival outcomes once diagnosed. Current therapeutic approaches mainly target the tumor cells or vasculature, but rarely take the immune factors into consideration.
In our study, the compositions of tumor-infiltrating immune cells (TIICs) in liver cancer and paracancer samples were analyzed based on the gene expression profiles by CIBERSORT. After calculating the proportions of 22 TIICs subtypes in 51 paired cancer and paracancer samples, we found their proportions varied between intragroup and intergroup. Compared with the paracancer tissues, the relative proportions of macrophages M0 and resting mast cells in liver cancer samples were significantly elevated, while that of M2 macrophages were reduced.
Univariate Cox regression analysis with the 22 TIICs subtypes as continuous variables showed increased B cells memory and resting NK cells were significantly associated with poor survival outcome. Besides, hierarchical clustering analysis based on the proportions of 22 TIICs subtypes identified 3 clusters, which exhibited distinct prognosis. Among them, cluster 1 had superior survival outcomes, while cluster 3 had inferior survival outcomes.
Collectively, our research suggested certain TIICs subpopulations proportions, as well as cluster patterns were associated with the prognosis of liver cancer, which provided potential therapeutic targets for liver cancer.
肝癌是最致命的恶性肿瘤之一,一旦确诊,生存预后较差。目前的治疗方法主要针对肿瘤细胞或血管,但很少考虑免疫因素。
在我们的研究中,通过 CIBERSORT 基于基因表达谱分析了肝癌和癌旁样本中肿瘤浸润免疫细胞(TIICs)的组成。在计算了 51 对癌和癌旁样本中 22 种 TIIC 亚型的比例后,我们发现它们在组内和组间的比例存在差异。与癌旁组织相比,肝癌样本中巨噬细胞 M0 和静止肥大细胞的相对比例明显升高,而 M2 巨噬细胞的比例降低。
将 22 种 TIICs 亚型作为连续变量进行单因素 Cox 回归分析显示,记忆 B 细胞和静止 NK 细胞的增加与不良生存结局显著相关。此外,基于 22 种 TIICs 亚型比例的层次聚类分析确定了 3 个聚类,它们表现出不同的预后。其中,簇 1 具有较好的生存结局,而簇 3 具有较差的生存结局。
综上所述,我们的研究表明某些 TIICs 亚群比例以及聚类模式与肝癌的预后相关,为肝癌提供了潜在的治疗靶点。