Prognostic value of LECT2 and relevance to immune infiltration in hepatocellular carcinoma.
Prognostic value of LECT2 and relevance to immune infiltration in hepatocellular carcinoma.
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LECT2 的预后价值及其与肝细胞癌免疫浸润的相关性
DOI：
10.3389/fgene.2022.951077
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发表时间：
2022
影响因子：
3.7
通讯作者：
Xu, Honghai
中科院分区：
文献类型：
--
作者：
Qin, Jiangfeng;Sun, Weijie;Zhang, Hui;Wu, Zihao;Shen, Jiapei;Wang, Wenhai;Wei, Yuanyuan;Liu, Yanyan;Gao, Yufeng;Xu, Honghai
背景：已有研究表明，白细胞源性趋化因子2（LECT 2）与肝癌的发生发展有关。然而，目前还没有研究全面分析LECT 2在肝细胞癌（HCC）中的作用。 方法：应用TCGA数据集分析LECT 2在HCC中的表达。此外，还研究了LECT 2在HCC中的预后价值。DriverDBv 3用于分析LECT 2的突变、CNV和甲基化谱。并在72例HCC标本中进行了免疫组化验证。分析LECT 2的预后价值及其与临床病理特征的相关性。使用R软件包进行LECT 2共表达的GO/KEGG富集分析和基因集富集分析（GSEA）。PPI相互作用网络由检索工具检索相互作用基因（STRING）数据库构建。采用XCELL、TIMER、QUANTISEQ、MCPCOUNTER、EPIC、CIBERSORT abs和CIBERSORT算法评估免疫浸润，并使用斯皮尔曼分析其与LECT 2的相关性。此外，我们分析了LECT 2表达与免疫检查点分子和HLA基因的相关性。最后，我们通过pRRophetic软件包分析了六种化疗药物的IC 50值。 结果：在HCC患者中发现LECT 2表达水平降低。此外，LECT 2水平降低与总生存期、无病生存期、疾病特异性生存期和无进展生存期相关。此外，甲基化与LECT 2表达显著相关。功能富集分析显示，LECT 2可能通过多种途径影响HCC进展，如JAK/STAT信号通路、细胞周期和癌症中的途径。LECT 2的表达与B细胞、中性粒细胞、单核细胞、癌相关成纤维细胞、髓系树突状细胞的免疫浸润呈负相关，与T细胞CD 8+幼稚细胞、内皮细胞、造血干细胞的免疫浸润呈正相关。LECT 2表达与多种免疫检查点分子和HLA基因呈负相关。化疗敏感性分析显示LECT 2高表达组化疗敏感性较低。我们验证了LECT 2的预后价值，临床病理特征分析显示LECT 2高表达组TNM分期较低。 结论：LECT 2在肝癌组织中的低表达与预后不良密切相关，其独特的免疫学效应可能具有潜在的临床应用价值。
Background: Previous studies have shown that Leukocyte cell-derived chemotaxin2 (LECT2) is associated with the development of HCC. However, there are still no studies with a comprehensive analysis of the role of LECT2 in hepatocellular carcinoma (HCC). Methods: TCGA data sets were used to analyze the expression of LECT2 in HCC. In addition, the prognostic value of LECT2 in HCC was also investigated. DriverDBv3 was used to analyze the Mutation, CNV, and methylation profiles of LECT2. And, validated by immunohistochemistry in 72 HCC samples. The prognostic value of LECT2 and the correlation with clinicopathological features were analyzed. The GO/KEGG enrichment analysis of LECT2 co-expression and gene set enrichment analysis (GSEA) was performed using the R software package. The PPI interaction network was constructed by Search Tool for the Retrieval of Interacting Genes (STRING) database. Immune infiltration was estimated by the XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT abs and CIBERSORT algorithms, and Spearman was used to analyzing their correlation with LECT2. Moreover, we analyzed the correlation of LECT2 expression with immune checkpoint molecules and HLA genes. Finally, we analyzed the IC50 values of six chemotherapeutic drugs by the pRRophetic package. Results: Reduced LECT2 expression levels found in HCC patients. Moreover, decreased levels of LECT2 were associated with poor overall survival, disease-free survival, disease-specific survival, and progression-free survival. Besides, methylation was significantly associated with LECT2 expression. The functional enrichment analysis revealed that LECT2 may affect HCC progression through various pathways such as JAK/STAT signaling pathway, cell cycle, and pathways in cancer. Additionally, the results showed that LECT2 expression was negatively correlated with immune infiltration of B cells, Neutrophil, Monocyte, Cancer-associated fibroblast, and Myeloid dendritic cell, and positively correlated with T cell CD8+ naive, Endothelial cell, and Hematopoietic stem cell. LECT2 expression was negatively correlated with multiple immune checkpoint molecules and HLA genes. Chemosensitivity analysis showed that chemosensitivity was lower in the LECT2 high expression group. We validated the prognostic value of LECT2 and analysis of clinicopathological features showed a lower TNM stage in the group with high expression of LECT2. Conclusion: Low expression of LECT2 in HCC is closely associated with poor prognosis, LECT2 may have potential clinical applications due to its unique immunological effects.
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影响因子：
64.5
作者：
McGranahan N;Rosenthal R;Hiley CT;Rowan AJ;Watkins TBK;Wilson GA;Birkbak NJ;Veeriah S;Van Loo P;Herrero J;Swanton C;TRACERx Consortium
通讯作者：
TRACERx Consortium
影响因子：
13.5
作者：
L'Hermitte, Antoine;Pham, Sandrine;Couty, Jean-Pierre
通讯作者：
Couty, Jean-Pierre
影响因子：
4.4
作者：
Yamagoe, S;Yamakawa, Y;Suzuki, K
通讯作者：
Suzuki, K
EYA2 通过 SOCS3 介导的 JAK/STAT 信号传导阻断来抑制肝细胞癌的进展
影响因子：
37.3
作者：
Liu ZK;Li C;Zhang RY;Wei D;Shang YK;Yong YL;Kong LM;Zheng NS;Liu K;Lu M;Liu M;Hu CX;Yang XZ;Chen ZN;Bian H
通讯作者：
Bian H
DOI：
10.1111/cts.12469
发表时间：
2017-07
期刊：
Clinical and translational science
影响因子：
--
作者：
Slowik V;Apte U
通讯作者：
Apte U