基于癌症基因组图谱数据库结直肠癌免疫细胞浸润预测模型的建立

doi:10.19723/j.issn.1671-167X.2022.02.001

摘要/Abstract

摘要：

目的: 研究结直肠癌组织的免疫细胞浸润与临床预后之间的相关性。方法: 从癌症基因组图谱(the can-cer genome atlas,TCGA)中提取结直肠癌数据,基于反卷积算法(CIBERSORT)分析评估结直肠癌组织中22种肿瘤浸润性免疫细胞(tumor-infiltrating immune cells,TIICs)的浸润模式,以确定不同TIICs表达程度与5年生存率之间的关联。使用条形图展示结直肠癌样本中TIICs比例,绘制矩阵图分析不同TIICs之间的相关性。结果: 共从 TCGA数据库中提取了473例结直肠癌组织和41个正常对照组织,对比分析表明,结直肠癌组织中各种TIICs比例存在差异。在研究的细胞亚群中,结直肠癌组织中M0、M1和M2巨噬细胞和单核细胞的比例相对较高,而B细胞和中性粒细胞的比例相对较低。TIICs的比例与患者的TNM分期及临床分级显著相关:静息NK细胞、CD8⁺T细胞、浆细胞与T期相关,活化树突状细胞与N期相关,嗜酸性粒细胞、M1巨噬细胞及活化肥大细胞与M期相关,M1巨噬细胞和单核细胞与临床分级相关。生存分析结果显示,活化的树突状细胞与结直肠癌患者的5年生存率呈正相关,幼稚CD4⁺T细胞与5年生存率呈负相关。结论: 分析结直肠癌患者肿瘤组织TIICs亚群比例具有潜在的临床预后价值,可通过其识别可能从化疗中受益的患者,并预测新药的可能靶点。

关键词: 淋巴细胞, 肿瘤浸润, 结直肠肿瘤, 基因数据库, 列线图, 临床病理特征

Abstract:

Objective: To study the correlation between immune cell infiltration in colorectal cancer tissue and clinical prognosis and to explore the levels of some immune cell genes for predicting the prognosis of patients with glioma colorectal cancer. Methods: In this study, we extracted colorectal cancer data from the cancer genome atlas (TCGA). Based on a deconvolution algorithm (called CIBERSORT) and clinically annotated expression profiles, the analysis assessed the infiltration patterns of 22 immune cells in colorectal cancer tissue to determine the association between each cell type and survival. Differences in five-year survival rate effectively illustrate the clinical prognostic value of each immune cell proportion in colorectal cancer, using a bar graph, correlation-based heatmap to represent the proportion of immune cells in each colorectal cancer sample. Results: A total of 473 colorectal cancer tissues and 41 normal control tissues were extracted from the TCGA database, and the comparative analysis showed that there were differences in the proportion of various TIICs in colorectal cancer tissues, which could characterize individual differences and have prognostic value. Among the cell subsets studied, the proportions of memory B cells, plasma cells, CD4⁺ T cells, natural killer (NK) cells, M0 macrophages, M2 macrophages, and activated mast cells were significantly different between normal and cancer tissues. Resting NK cells, CD8⁺ T cells, and plasma cells were associated with T phase, activated dendritic cells were associated with N phase, and eosinophils, M1 macrophages, and activated mast cells were associated with M phase. Survival analysis showed that activated dendritic cells were positively associated with five-year survival rate in colorectal cancer patients. Naive CD4⁺ T cells were inversely associated with five-year survival rate. Conclusion: There are different degrees of immune cell infiltration in colorectal cancer tissues, and these differences may be important determinants of prognosis and treatment response. We conducted a new gene expression-based study of immune cell subtype levels and prognosis in colorectal cancer, which has potential clinical prognostic value in colorectal cancer patients.

Key words: Lymphocytes, tumor-infiltrating, Colorectal neoplasms, Genetic databases, Nomogram, Clinicopathological characteristics

中图分类号:

R730.51

丁婷婷,曾楚雄,胡丽娜,余明华. 基于癌症基因组图谱数据库结直肠癌免疫细胞浸润预测模型的建立[J]. 北京大学学报（医学版）, 2022, 54(2): 203-208.

DING Ting-ting,ZENG Chu-xiong,HU Li-na,YU Ming-hua. Establishment of a prediction model for colorectal cancer immune cell infiltration based on the cancer genome atlas (TCGA) database[J]. Journal of Peking University (Health Sciences), 2022, 54(2): 203-208.

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Characteristics	n (%)
Gender
Male	238 (50.4)
Female	235 (49.6)
Vital status
Living	88 (18.6)
Deceased	385 (81.4)
Clinical stage
StageⅠ-Ⅱ	254 (53.7)
Stage Ⅲ-Ⅳ	219 (46.3)
T stage
T1	10 (2.1)
T2	77 (16.3)
T3	308 (65.1)
T4	78 (16.5)
N stage
N0	270 (57.1)
N1	103 (21.8)
N2	100 (21.1)
M stage
M0	334 (70.6)
M1	62 (23.1)
Mx	77 (16.3)