CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
泛癌分析揭示 CD19 作为肿瘤免疫标志物的预后与免疫治疗意义
英文原题：The Pan-Cancer Analysis Uncovers the Prognostic and Immunotherapeutic Significance of CD19 as an Immune Marker in Tumor.
查看英文原题
The Pan-Cancer Analysis Uncovers the Prognostic and Immunotherapeutic Significance of CD19 as an Immune Marker in Tumor.
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研究概要
该研究揭示了 CD19 作为预测性生物标志物以及不同癌症免疫治疗靶点的潜力。
中文摘要
抗 CD19 嵌合抗原受体（CAR）T 细胞疗法具有特异性细胞毒作用，使既往接受过 B 细胞恶性肿瘤治疗者取得了显著结局。然而，CD19 阳性靶细胞可能对部分实体瘤产生抗肿瘤免疫作用，其具体生物学功能仍有待阐明。
我们从癌症基因组图谱（TCGA）、肿瘤免疫估计资源（TIMER）、基因型组织表达数据库（GTEx）和人类蛋白质图谱（HPA）等多个数据库收集肿瘤和正常样本中 CD19 mRNA 及蛋白表达水平。通过 Kaplan-Meier（KM）分析和单变量 Cox 回归，评估 CD19 表达与患者预后的关系。随后使用 ESTIMATE 算法估算恶性肿瘤组织中的免疫细胞浸润比例，并使用 GSCALite 数据库评估 CD19 表达型肿瘤对化疗药物的敏感性。最后，通过免疫组织化学对部分癌种临床样本进行验证。
除结肠腺癌（COAD）外，多数肿瘤类型的 CD19 表达模式存在差异。CD19 在 9 种不同肿瘤中显示出早期诊断价值，其过表达可能延长患者生存期。多种肿瘤中 CD19 表达与肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）及 ESTIMATE 评分呈正相关。此外，CD19 表达与免疫细胞浸润存在直接关联，在乳腺浸润性癌（BRCA）中尤为明显。CD19 对多种化疗药物也高度敏感。
本研究揭示 CD19 可能同时作为预测性生物标志物和多种癌症免疫疗法的靶点。
展开英文摘要原文
The specific cytotoxic effects of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy have led to impressive outcomes in individuals previously treated for B-cell malignancies. However, the specific biological role of CD19(+) target cells, which exert antitumor immunity against some solid tumors, remains to be elucidated.
We collected information regarding the level of CD19 mRNA and protein expression from various databases including The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) for both tumor and normal samples. To evaluate the patient's prognosis according to CD19 expression, a Kaplan-Meier (KM) analysis and univariate Cox regression were performed. Furthermore, using the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using the Expression Data (ESTIMATE) algorithm, we estimated the ratio of immune cells infiltrating malignant tumor tissues. Afterward, the GSCALite repository was employed to evaluate the vulnerability of tumors expressing CD19 to drugs used in chemotherapy. To validate the results in clinical samples of certain cancer types, immunohistochemistry was then performed.
Most tumor types exhibited CD19 expression differently, apart from colon adenocarcinoma (COAD). The early diagnostic value of CD19 has been demonstrated in 9 different tumor types, and the overexpression of CD19 has the potential to extend the survival duration of patients. Multiple tumors showed a positive correlation between CD19 expression and tumor mutation burden (TMB), microsatellite instability (MSI), and ESTIMATE score. Furthermore, a direct association was discovered between the expression of CD19 and the infiltration of immune cells, particularly in cases of breast invasive carcinoma (BRCA). Moreover, CD19 is highly sensitive to a variety of chemotherapy drugs.
The study reveals the potential of CD19 as both a predictive biomarker and a target for different cancer immunotherapies.
论文信息
- 作者
- Wei L、Meng J、Xiang D、Yang Q、Zhou Y、Xu L、Chen J、Han Y
- 单位
- Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People's Republic of China.China
- 期刊
- International journal of general medicine2024
- 原文标识
- PubMed 38855424 · DOI 10.2147/IJGM.S459914
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