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基于基因共表达网络分析鉴定肝细胞癌中的免疫浸润细胞相关生物标志物。

Identification of immune-infiltrating cell-related biomarkers in hepatocellular carcinoma based on gene co-expression network analysis.

机构信息

Department of Gastroenterology, The Second People's Hospital of Liaocheng City, No.306 Jiankang Street, Linqing City, 252600, Shandong Province, China.

出版信息

Diagn Pathol. 2021 Jul 4;16(1):57. doi: 10.1186/s13000-021-01118-y.

DOI:10.1186/s13000-021-01118-y
PMID:34218795
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8255019/
Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is often caused by chronic liver infection or inflammation. Searching for potential immunotherapy targets will aid the early diagnosis and treatment of HCC.

METHODS

Firstly, detailed HCC data were downloaded from The Cancer Genome Atlas database. GDCRNATools was used for the comprehensive analysis of RNA sequencing data. Subsequently, the CIBERSORT package was used to estimate infiltration scores of 22 types of immune cells in complex samples. Furthermore, hub genes were identified via weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis. In addition, multiple databases were used to validate the expression of hub gene in the tumor tissue. Finally, prognostic, diagnostic and immunohistochemical analysis of key hub genes was performed.

RESULTS

In the present study, 9 hub genes were identified using WGCNA and PPI network analysis. Furthermore, the expression levels of 9 genes were positively correlated with the infiltration levels of CD8-positive T (CD8 T) cells. In multiple dataset validations, the expression levels of CCL5, CXCR6, CD3E, and LCK were decreased in cancer tissues. In addition, survival analysis revealed that patients with LCK low expression had a poor survival prognosis (P < 0.05). Immunohistochemistry results demonstrated that CCL5, CD3E and LCK were expressed at low levels in HCC cancer tissues.

CONCLUSION

The identification of CCL5, CXCR6, CD3E and LCK may be helpful in the development of early diagnosis and therapy of HCC. LCK may be a potential prognostic biomarker for immunotherapy for HCC.

摘要

背景

肝细胞癌（HCC）通常由慢性肝脏感染或炎症引起。寻找潜在的免疫治疗靶点将有助于 HCC 的早期诊断和治疗。

方法

首先，从癌症基因组图谱数据库中下载详细的 HCC 数据。使用 GDCRNATools 对 RNA 测序数据进行综合分析。随后，使用 CIBERSORT 程序包估计复杂样本中 22 种免疫细胞的浸润分数。此外，通过加权基因共表达网络分析（WGCNA）和蛋白质-蛋白质相互作用（PPI）网络分析鉴定枢纽基因。此外，使用多个数据库验证肿瘤组织中枢纽基因的表达。最后，对关键枢纽基因进行预后、诊断和免疫组织化学分析。

结果

本研究通过 WGCNA 和 PPI 网络分析鉴定了 9 个枢纽基因。此外，9 个基因的表达水平与 CD8 阳性 T（CD8 T）细胞的浸润水平呈正相关。在多个数据集的验证中，CCL5、CXCR6、CD3E 和 LCK 的表达水平在癌组织中降低。此外，生存分析显示 LCK 低表达的患者生存预后较差（P<0.05）。免疫组织化学结果表明，CCL5、CD3E 和 LCK 在 HCC 癌组织中低表达。

结论

鉴定 CCL5、CXCR6、CD3E 和 LCK 可能有助于 HCC 的早期诊断和治疗。LCK 可能是 HCC 免疫治疗的潜在预后生物标志物。

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