Identification of LSM Family Members as Novel Unfavorable Biomarkers in Hepatocellular Carcinoma.
Identification of LSM Family Members as Novel Unfavorable Biomarkers in Hepatocellular Carcinoma.
复制标题
DOI：
10.3389/fonc.2022.871771
复制
发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
史密斯样（LSM）家族成员在几种类型的恶性肿瘤的多种肿瘤学过程中发挥关键作用。对肝癌LSM家族成员的研究可能为肝癌的发生和治疗提供新的思路。通过多种生物信息学方法和体外研究评估LSM家族成员的临床意义和肿瘤生物学功能。还使用单样本基因集富集分析（ssGSEA）和ESTIMATE算法研究了LSM家族成员与肿瘤免疫之间的潜在相关性。LSM家族成员在HCC中的过度表达与不良的临床结局显著相关，如较高的TNM分期、较高的组织学分级和较差的预后。基于LSM 5、LSM 10、LSM 12和LSM 14 B的风险评分系统显示出对HCC患者OS的可靠预测能力。功能富集分析表明LSM家族成员均参与细胞周期相关的生物学过程。此外，发现LSM 12、LSM 14 A和LSM 14 B与PI 3 K-Akt-mTOR和T细胞受体信号通路显著相关。LSM 12、LSM 14 A和LSM 14 B过表达的肿瘤显示活化CD 8 + T细胞浸润较低，溶细胞活性和免疫评分下降，但Th 2细胞和Th 2/Th 1浸润增加。LSM 12、LSM 14 A和LSM 14 B过表达也与较高的肿瘤相关免疫检查点（例如，PD-L1、B7-H3和PVR）表达和对免疫检查点阻断（ICB）的治疗不敏感性增加。此外，LSM 12、LSM 14 A和LSM 14 B的敲低显著抑制HCC细胞的增殖和侵袭。本研究系统地研究了LSM家族成员在肝癌中的表达模式和生物学价值，并确定了LSM家族成员作为肝癌治疗的新靶点。
Smith-like (LSM) family members play critical roles in multiple oncologic processes in several types of malignancies. The study on LSM family members of HCC might provide new insights into the tumorigenesis and therapeutic strategies of HCC. The clinical significance and oncologic biological functions of LSM family members were assessed through multiple bioinformatics methods and in vitro studies. The potential correlation between LSM family members and tumor immunity was also investigated using single sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm. LSM family member overexpression in HCC was significantly correlated with poor clinical outcomes such as higher TNM stage, advanced histologic grade, and worse prognosis. A risk score system based on LSM5, LSM10, LSM12, and LSM14B showed a reliable predictive ability for OS of HCC patients. Functional enrichment analysis demonstrated that LSM family members overexpressed were all involved in cell cycle related biological processes. Besides, LSM12, LSM14A, and LSM14B were found to be significantly associated with PI3K-Akt-mTOR and T cell receptor signaling pathways. Tumors with LSM12, LSM14A, and LSM14B overexpression exhibited lower infiltration of activated CD8+ T cells with declined cytolytic activity and immune score, but increased infiltration of Th2 cells and Th2/Th1. LSM12, LSM14A, and LSM14B overexpression is also associated with higher tumor-related immune checkpoints (e.g., PD-L1, B7-H3, and PVR) expression and increased therapeutic insensitivity to immune checkpoint blockade (ICB). Moreover, the knockdown of LSM12, LSM14A, and LSM14B significantly inhibited the proliferation and invasion of HCC cells. This study systematically investigated the expression pattern and biological values of LSM family members in HCC and identified LSM family members as novel therapeutic targets in HCC.
登录
查看更多内容
表观遗传调控与基因治疗介导的免疫检查点阻断相结合可诱导体内抗肿瘤作用和免疫反应
影响因子：
16.6
作者：
Fang H;Guo Z;Chen J;Lin L;Hu Y;Li Y;Tian H;Chen X
通讯作者：
Chen X
影响因子：
11.4
作者：
Achsel, T;Brahms, H;Lührmann, R
通讯作者：
Lührmann, R
影响因子：
11.2
作者：
Fraser, MM;Watson, PM;Watson, DK
通讯作者：
Watson, DK
肝移植后的急性排斥反应不太常见，但预示着 HBV 相关肝细胞癌患者的预后会更好
影响因子：
6.6
作者：
Mao, Jia-Xi;Guo, Wen-Yuan;Ding, Guo-Shan
通讯作者：
Ding, Guo-Shan
影响因子：
5.8
作者：
Farzaneh Z;Vosough M;Agarwal T;Farzaneh M
通讯作者：
Farzaneh M