鉴定肝癌患者 PBMC 中的免疫相关靶标和预后生物标志物。
Identification of immune-related target and prognostic biomarkers in PBMC of hepatocellular carcinoma.
机构信息
Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Futian District, Shenzhen, 518033, Guangdong Province, China.
Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
出版信息
BMC Gastroenterol. 2023 Jul 12;23(1):234. doi: 10.1186/s12876-023-02843-y.
BACKGROUND
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and is characterized by insidious onset, rapid progression, and poor prognosis. Immunotherapy is a first-line treatment for advanced HCC. The identification of immune-related prognostic markers may be an effective strategy to predict and improve clinical response rate of immunotherapy.
METHODS
The DESeq2, edgeR, and limma R packages were used to compare the transcriptomes of HCC with different prognoses. Cancer-related databases such as UALCAN, TNMplot, GEPIA, muttarget and Human Protein Atlas (HPA), and the Kaplan-Meier Plotter platform were used to analyze the relationship between CLDN18 and the clinical characteristics, as well as prognosis of HCC. The co-expressed genes of CLDN18 were obtained from LinkedOmics platform, and GO functional enrichment and KEGG pathway analysis were performed. The CIBERSORT, TIMER, Timer 2.0 and TISIDB algorithms were used to analyze immune infiltration.
RESULTS
CLDN18 was differentially expressed in HCC patients with different prognoses, and its expression level in PBMC was positively correlated with the stage of BCLC. In addition, CLDN18 was significantly overexpressed in HCC tumor tissues compared to adjacent non-tumor tissues, which was consistent with PBMC sequencing results and immunohistochemical data from human protein profiles. CLDN18 was also positively correlated with HCC staging and grading, and high expression levels of CLDN18 predicted shorter overall survival. Functional annotation of CLDN18 in HCC revealed enrichment of the cellular senescence and protein activation cascade, along with biological processes such as cell cycle, inflammatory response, and cellular ketone metabolism. In addition, CLDN18 was also associated with tumor infiltrating immune cells, suppressive immune cell markers, T lymphocyte depletion and activation of HCC, and low expression of CLDN18 was associated with higher CD8 + T cell infiltration and better survival rates.
CONCLUSIONS
CLDN18 is a potential prognostic marker and immunotherapeutic target for HCC.
背景
肝细胞癌（HCC）是全球癌症相关死亡的第三大原因，其特点是发病隐匿、进展迅速、预后不良。免疫疗法是治疗晚期 HCC 的一线治疗方法。鉴定与免疫相关的预后标志物可能是预测和提高免疫治疗临床反应率的有效策略。
方法
使用 DESeq2、edgeR 和 limma R 包比较不同预后 HCC 的转录组。使用 UALCAN、TNMplot、GEPIA、muttarget 和 Human Protein Atlas（HPA）等癌症相关数据库以及 Kaplan-Meier Plotter 平台分析 CLDN18 与 HCC 的临床特征和预后的关系。从 LinkedOmics 平台获取 CLDN18 的共表达基因，并进行 GO 功能富集和 KEGG 通路分析。使用 CIBERSORT、TIMER、Timer 2.0 和 TISIDB 算法分析免疫浸润。
结果
CLDN18 在不同预后 HCC 患者中差异表达，其在 PBMC 中的表达水平与 BCLC 分期呈正相关。此外，CLDN18 在 HCC 肿瘤组织中的表达明显高于相邻非肿瘤组织，这与 PBMC 测序结果和人类蛋白质图谱的免疫组化数据一致。CLDN18 还与 HCC 分期和分级呈正相关，高表达水平的 CLDN18 预示着总生存期更短。CLDN18 在 HCC 中的功能注释显示细胞衰老和蛋白激活级联的富集，以及细胞周期、炎症反应和细胞酮代谢等生物学过程。此外，CLDN18 还与肿瘤浸润免疫细胞、抑制性免疫细胞标志物、T 淋巴细胞耗竭和 HCC 激活有关，CLDN18 低表达与 CD8+T 细胞浸润更高和生存率更高有关。
结论
CLDN18 是 HCC 的一个潜在的预后标志物和免疫治疗靶点。
Zotero 插件