ADAM12as a Clinical Prognostic Indicator Associated with Tumor Immune Infiltration in Lung Adenocarcinoma

生物 基因敲除 免疫系统 腺癌 癌症研究 生物标志物 肺癌 免疫疗法 免疫组织化学 细胞 基因 临床意义 基因表达 蛋白水解酶 生存分析 基质金属蛋白酶 细胞外 癌症 基因表达谱 细胞粘附 免疫学 细胞培养 肿瘤科 肺腺癌
作者
Junfan Pan,Zhidong Huang,Yuan Zhang,Yiquan Xu
出处
期刊:DNA and Cell Biology [Mary Ann Liebert, Inc.]
卷期号:41 (4): 410-423 被引量:6
标识
DOI:10.1089/dna.2021.0764
摘要

Twenty-two functional α-disintegrin and metalloproteinases (ADAMs) have been identified in humans, 12 of which have proteolytic activity. The role of ADAMs in cancer has attracted increasing attention. However, the expression and significance of ADAMs in lung adenocarcinoma (LUAD) remain unclear. Most recently, we investigated the transcriptional data of ADAMs and related overall survival in patients with LUAD based on several databases, including TCGA, cBioPortal, Kaplan-Meier Plotter, LinkedOmics, KEGG, TIMER, and TISIDB. Knockdown of ADAM12 was performed in vitro to verify its biological function. According to our findings, 10 ADAMs exhibited significant differential expression in LUAD compared with cancer-adjacent normal tissues. ADAM12 expression was significantly higher in LUAD tissues than in paracancerous tissues, and lower ADAM12 expression was associated with better survival. Genetic alterations of ADAM12 mainly included missense mutations, amplifications, and deep deletions. ADAM12 and positively correlated genes were mainly enriched in protein digestion and absorption, extracellular matrix-receptor interaction, and adhesion plaques. ADAM12 had a moderate correlation with immune cell markers EBIP1, CCNB1, EXO1, KNTC1, PRC1, and FAM198B. Prognostic model was established based on ADAM12 and immune-related genes. In vitro experiments revealed that knocking down ADAM12 inhibited cell proliferation, migration, and invasion. ADAM12 potentially plays an important role in the occurrence of LUAD and may be utilized as an immunotherapy target and a valuable prognostic biomarker for LUAD.
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