Department of Medical Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Clin Transl Oncol. 2021 Sep;23(9):1923-1933. doi: 10.1007/s12094-021-02602-z. Epub 2021 Mar 25.
Colorectal cancer is one of the most common malignancies. With continuous exploration of the interaction between tumor cells and the immune system, tumor immunotherapy has become a revolution. However, CRC remains one of the less effective tumors for immunotherapy. The tumor microenvironment plays an important role in tumorigenesis and progression. The aim of this study is to explore tumor microenvironment-related genes that can predict the prognosis of colorectal adenocarcinoma, and also to provide new ideas for the mechanism of tumor development as well as immunotherapy.
After estimating Stromalscore and Immunescore of colorectal adenocarcinoma tumor samples according to RNA-Seq expression data downloaded from TCGA, we screened for TME-related differential genes. We filtered prognosis-related core genes by constructing protein-protein interaction networks and making one-factor cox analysis for prognosis. Finally, the relative content of 22 immune cells in tumor tissues was evaluated, and then immune cells associated with core genes were identified.
We screened 773 differential genes related to the TME. Then we identified C3 as a core gene associated with prognosis. Single gene analysis showed that C3 expression was significantly higher in tumor tissues than in normal tissues (p < 0.001). High C3 expression was associated with lower overall survival (p = 0.046). Tumor immune cell analysis showed that mast cells resting, mast cells activated, T cells CD4 memory activated, eosinophils, and macrophages M0 were C3-associated immune cells.
C3 has potential as a biomarker for colorectal adenocarcinoma and could provide new research ideas for the diagnosis and treatment of colorectal adenocarcinoma, especially for immunotherapy.
结直肠癌是最常见的恶性肿瘤之一。随着对肿瘤细胞与免疫系统相互作用的不断探索，肿瘤免疫治疗已成为一场革命。然而，CRC 仍然是免疫治疗效果较差的肿瘤之一。肿瘤微环境在肿瘤的发生和发展中起着重要作用。本研究旨在探索与肿瘤微环境相关的基因，这些基因可以预测结直肠腺癌的预后，并为肿瘤发生机制以及免疫治疗提供新的思路。
根据从 TCGA 下载的 RNA-Seq 表达数据，估计结直肠腺癌肿瘤样本的基质评分和免疫评分后，筛选出与 TME 相关的差异基因。通过构建蛋白质-蛋白质相互作用网络并对预后进行单因素 cox 分析，筛选出与预后相关的核心基因。最后，评估肿瘤组织中 22 种免疫细胞的相对含量，并确定与核心基因相关的免疫细胞。
我们筛选出 773 个与 TME 相关的差异基因。然后我们确定 C3 是一个与预后相关的核心基因。单基因分析表明，C3 在肿瘤组织中的表达明显高于正常组织（p<0.001）。C3 高表达与总生存期降低相关（p=0.046）。肿瘤免疫细胞分析表明，静止肥大细胞、激活肥大细胞、CD4 记忆激活 T 细胞、嗜酸性粒细胞和 M0 巨噬细胞是与 C3 相关的免疫细胞。
C3 可能成为结直肠腺癌的生物标志物，并为结直肠腺癌的诊断和治疗，特别是免疫治疗提供新的研究思路。
