Luo Yi, Cai Jie, Yin Yanze, Xia Qiang
Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Engineering Research Center of Transplantation and Immunology, Shanghai, China.
Transl Cancer Res. 2024 Oct 31;13(10):5446-5457. doi: 10.21037/tcr-24-492. Epub 2024 Oct 29.
Patients diagnosed with hepatocellular carcinoma (HCC) generally have an unfavorable outlook, with lung metastasis being a prevalent factor contributing to mortality. The metastatic microenvironment is critical to the tumor metastatic process. The exact impact of Triggering Receptor Expressed on Myeloid Cells 1 (TREM1) on tumor metastasis and the microenvironment of metastasis is still not known. By analyzing online databases and a clinical cohort, we evaluated the predictive significance of TREM1 and its correlation with the tumor microenvironment (TME).
Using the Gene Expression Omnibus (GEO) dataset (GSE141016), genes differentially expressed in liver cancer and lung metastases were analyzed. Data from liver hepatocellular carcinoma (LIHC) of The Cancer Genome Atlas (TCGA) were acquired through RNA sequencing. The abundance of tumor-infiltrating immune cells was estimated using Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE). The single sample gene set enrichment analysis (ssGSEA) algorithm was utilized to determine the association between TREM1 and immune cells. The level of TREM1 and immune cells were determined in formalin-fixed paraffin-embedding (FFPE) specimens.
Increased expression of TREM1 in HCC was linked to a poorer clinical prognosis and elevated incidence of lung metastasis. Furthermore, TREM1 was found to be associated with multiple immune cells in the TME. We noticed that lung metastases in the same patient had higher levels of TREM1 protein compared to primary liver cancer. Additionally, lung metastases exhibited increased neutrophil numbers and neutrophil extracellular traps (NETs) formation compared to primary liver cancer. Moreover, there was a positive correlation between TREM1 and both neutrophils and NETs.
Increased expression of TREM1 in HCC is linked to a poorer clinical outlook and elevated incidence of lung metastasis, suggesting its potential as a prognostic biomarker for patients with liver cancer lung metastasis.
被诊断为肝细胞癌(HCC)的患者总体预后不佳,肺转移是导致死亡的常见因素。转移微环境对肿瘤转移过程至关重要。髓系细胞表达的触发受体1(TREM1)对肿瘤转移及转移微环境的确切影响尚不清楚。通过分析在线数据库和一个临床队列,我们评估了TREM1的预测意义及其与肿瘤微环境(TME)的相关性。
使用基因表达综合数据库(GEO)数据集(GSE141016),分析在肝癌和肺转移中差异表达的基因。通过RNA测序获取癌症基因组图谱(TCGA)中肝细胞癌(LIHC)的数据。使用利用表达数据估计恶性肿瘤组织中的基质和免疫细胞(ESTIMATE)方法估计肿瘤浸润免疫细胞的丰度。采用单样本基因集富集分析(ssGSEA)算法确定TREM1与免疫细胞之间的关联。在福尔马林固定石蜡包埋(FFPE)标本中测定TREM1和免疫细胞的水平。
HCC中TREM1表达增加与较差的临床预后和较高的肺转移发生率相关。此外,发现TREM1与TME中的多种免疫细胞有关。我们注意到,同一患者的肺转移灶中TREM1蛋白水平高于原发性肝癌。此外,与原发性肝癌相比,肺转移灶中的中性粒细胞数量增加,中性粒细胞胞外陷阱(NETs)形成增多。而且,TREM1与中性粒细胞和NETs均呈正相关。
HCC中TREM1表达增加与较差的临床预后和较高的肺转移发生率相关,提示其有可能作为肝癌肺转移患者的预后生物标志物。