Song Caiyun, Chen Jionghuang, Zhang Chaolei, Dong Dapeng
Department of Gastroenterology, Wenzhou People's Hospital, Wenzhou, China.
Zhejiang Engineering Research Center of Cognitive Healthcare, School of Medicine, Zhejiang University, Hangzhou, China.
Front Oncol. 2022 Feb 23;12:849717. doi: 10.3389/fonc.2022.849717. eCollection 2022.
A Disintegrin and Metallopeptidase with Thrombospondin Type 1 Motif 12 (ADAMTS12), a member of the ADAMTS family of multidomain extracellular protease enzymes, is involved in the progression of many tumors. However, a pan-cancer analysis of this gene has not yet been performed. Its role in pancreatic adenocarcinoma (PAAD) also remains unclear.
The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression data (GTEx) databases were used to analyze ADAMTS12 expression in pan-cancer. We assessed the expression, clinical characteristics, prognostic significance, copy number alteration, methylation, and mutation of ADAMTS12 and its correlation with the tumor immune microenvironment. qRT-PCR and immunohistochemistry assays were also performed to validate the expression of ADAMTS12 in PAAD.
Through bioinformatics analysis and preliminary experimental verification, ADAMTS12 was found to be substantially overexpressed in PAAD. High expression level of ADAMTS12 was correlated with worse survival rates in patients with PAAD and high infiltration levels of tumor-associated macrophages, cancer-associated fibroblasts, immune checkpoint proteins, and immunosuppressive genes.
Our findings suggest ADAMTS12 as a potential prognostic biomarker in PAAD. Elevated ADAMTS12 expression may also indicate an immunosuppressive microenvironment.
含血小板反应蛋白基序的解聚素和金属蛋白酶12（ADAMTS12）是多结构域细胞外蛋白酶ADAMTS家族的成员，参与多种肿瘤的进展。然而，尚未对该基因进行泛癌分析。其在胰腺腺癌（PAAD）中的作用也仍不清楚。
使用癌症基因组图谱（TCGA）和基因型-组织表达数据（GTEx）数据库分析ADAMTS12在泛癌中的表达。我们评估了ADAMTS12的表达、临床特征、预后意义、拷贝数改变、甲基化和突变及其与肿瘤免疫微环境的相关性。还进行了qRT-PCR和免疫组织化学分析以验证ADAMTS12在PAAD中的表达。
通过生物信息学分析和初步实验验证，发现ADAMTS12在PAAD中显著过表达。ADAMTS12的高表达水平与PAAD患者较差的生存率以及肿瘤相关巨噬细胞、癌症相关成纤维细胞、免疫检查点蛋白和免疫抑制基因的高浸润水平相关。
我们的研究结果表明ADAMTS12是PAAD中一种潜在的预后生物标志物。ADAMTS12表达升高也可能表明存在免疫抑制微环境。
