肺癌
安非雷古林
医学
癌症研究
腺癌
肺
表皮生长因子受体
血栓反应素
靶向治疗
肿瘤科
转移
癌症
内科学
金属蛋白酶
基质金属蛋白酶
作者
Hsiao-Chen Lee,Chao‐Yuan Chang,Kwou‐Yeung Wu,Hung‐Hsing Chiang,Yung-Yun Chang,Lian-Xiu Liu,Yu‐Tung Huang,Jen‐Yu Hung,Ya‐Ling Hsu,Yu‐Yuan Wu,Yu-Chen Tsai
摘要
Lung cancer is well known for its high mortality worldwide. The treatment for advanced lung cancer needs more attention to improve its survival time. A disintegrin and metallopeptidase with thrombospondin motifs 8 (ADAMTS8) has been linked to several cancer types. However, its role in lung cancer is worthy of deep investigation to promote novel drug development. This study took advantage of RNA-seq and bioinformatics to verify the role that ADAMTS8 plays in lung cancer. The functional assays suggested that ADAMTS8 mediates invasion and metastasis when expressed at a low level, contributing to poor overall survival (OS). The expression of ADAMTS8 was under the regulation of GATA Binding Protein 1 (GATA1) and executed its pathologic role through Thrombospondin Type 1 Domain Containing 1 (THSD1) and ADAMTS Like 2 (ADAMTSL2). To define the impact of ADAMTS8 in the lung cancer treatment strategy, this study further grouped lung cancer patients in the TCGA database into mutated epidermal growth factor receptor (EGFR)/wild-type EGFR and programmed death ligand 1 (PD-L1) high/low groups. Importantly, the expression of ADAMTS8 was correlated positively with the recruitment of anticancer NKT cells and negatively with the infiltration of immunosuppressive Treg and exhausted T cells. The results indicated that lung cancer patients with higher ADAMTS8 levels among wild-type EGFR or low PD-L1 groups survive longer than those with lower levels do. This study indicates that ADAMTS8 might be a treatment option for patients with lung adenocarcinoma who lack efficient targeted or immunotherapies.
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