Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China.
Orthopedic Laboratory of Chongqing Medical University, 400016 Chongqing, China.
Front Biosci (Landmark Ed). 2024 Apr 12;29(4):151. doi: 10.31083/j.fbl2904151.
The extracellular matrix (ECM) modeling induced by the metalloproteinases is a vital characteristic for tumor progression. Previous studies mainly focus on the functions of two subgroups of metalloproteinases: matrix metalloproteinases (MMPs) and a disintegrin and metalloproteases (ADAMs) in tumors. The roles of another important group: the ADAMs with thrombospondin motifs (ADAMTS) remain unclear. This study aimed to perform a pan-cancer analysis of procollagen N-propeptidase subgroup of ADAMTS (PNPSA).
We systematically analyzed expression landscape, genomic variations, prognostic value, and cell expression clusters of PNPSA in pan-cancer based on the multiple integrated open databases. Besides, we also analyzed the impacts of expressions and genomic variations of PNPSA members on tumor immune microenvironment (TIME) and immune-related molecules in pan-cancer based on the immune-related open databases. The Gene Set Variation Analysis (GSVA) was performed to evaluate the associations of the whole PNPSA with prognosis, tumor indicators, TIME, and drug sensitivities. Meanwhile, the Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to reveal related signaling pathways. Finally, immunohistochemical staining was used to validate the differential analysis results.
We found a dual prognostic role of PNPSA members in pan-cancer and they were significantly correlated with TIME and immune-related molecules. Interestingly, the copy number variations (CNVs) of all PNPSA members were revealed to be negatively correlated with NK cell infiltration in most cancers. Single-cell sequencing analysis reveals expressions of PNPSA gene family members on some specific tumor and immune cells in addition to the fibroblasts. The GSVA score was found to have some predictive value for survival status in Brain Lower Grade Glioma (LGG), Mesothelioma (MESO), and Uveal Melanoma (UVM) and to be significantly correlated with tumorigenesis-related pathways such as PI3K-Akt, AGE-RAGE, etc. The GSVA score also shows some predictive value for chemotherapy and immunotherapy efficacy in some tumors.
PNPSA was correlated with tumor development and might be potential tumor biomarker and therapeutic target.
细胞外基质（ECM）的重塑是肿瘤进展的一个重要特征，这种重塑是由金属蛋白酶诱导的。以前的研究主要集中在金属蛋白酶的两个亚群：基质金属蛋白酶（MMPs）和解整合素金属蛋白酶（ADAMs）在肿瘤中的作用。另一个重要的亚群：富含血栓反应蛋白基序的解整合素金属蛋白酶（ADAMTS）的作用仍不清楚。本研究旨在对 ADAMTS 中前胶原 N 端肽酶亚群（PNPSA）进行泛癌分析。
我们基于多个综合开放数据库，系统地分析了 PNPSA 在泛癌中的表达谱、基因组变异、预后价值和细胞表达聚类。此外，我们还基于免疫相关的开放数据库，分析了 PNPSA 成员的表达和基因组变异对泛癌肿瘤免疫微环境（TIME）和免疫相关分子的影响。进行基因集变异分析（GSVA）以评估整个 PNPSA 与预后、肿瘤指标、TIME 和药物敏感性的相关性。同时，进行京都基因与基因组百科全书（KEGG）分析以揭示相关信号通路。最后，使用免疫组织化学染色验证差异分析结果。
我们发现 PNPSA 成员在泛癌中的双重预后作用，它们与 TIME 和免疫相关分子显著相关。有趣的是，所有 PNPSA 成员的拷贝数变异（CNVs）在大多数癌症中与 NK 细胞浸润呈负相关。单细胞测序分析显示，PNPSA 基因家族成员在一些特定的肿瘤和免疫细胞以及成纤维细胞上表达。GSVA 评分在脑低级别神经胶质瘤（LGG）、间皮瘤（MESO）和葡萄膜黑色素瘤（UVM）的生存状态中具有一定的预测价值，并且与 PI3K-Akt、AGE-RAGE 等肿瘤发生相关通路显著相关。GSVA 评分还对一些肿瘤的化疗和免疫治疗疗效具有一定的预测价值。
PNPSA 与肿瘤的发生发展有关，可能是潜在的肿瘤标志物和治疗靶点。
