Abstract
The “A Disintegrin and Metalloproteinase with Thrombospondin Motif” (ADAMTS) family of genes is involved in the occurrence and development of different cancers. However, the prognostic value of these genes in gastric cancer (GC) has not been revealed. The present study was thus conducted to determine the prognostic value for the ADAMTS family of genes in GC. First, we evaluated the mRNA expression levels of the ADAMTS family in GC patients using a GEPIA dataset. Thereafter, we determined the prognostic value of these genes by analyzing their mRNA level using the Kaplan–Meier Plotter database. The mRNA expression level of ADAMTS12 was randomly validated by qRT-PCR and meta-analysis while its coexpression genes were derived using Coexpedia. Finally, we performed Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using the OmicShare Tools. Compared to normal tissues, expression of ADAMTS2 and 12 was significantly higher while that of ADAMTS1, 13, and 15 was significantly lower in GC tissues. According to the RNA-seq and gene chip data, the ADAMTS family (6, 7, 12, 15, and 18) of genes was closely related to the prognosis of GC, and their high expression levels were associated with poor prognosis and survival time. In addition, ADAMTS12 was highly expressed in 20 pairs of GC tissues based on RT-PCR (P=0.016) and meta-analysis (SMD: 0.73, 95% CI: 0.32–1.14, P < 0.001). GO and KEGG pathway analyses indicated that the ADAMTS12 coexpressed genes were enriched in the pathways of extracellular matrix organization, extracellular matrix structural constituent, extracellular matrix, and protein digestion and absorption. Herein, we discovered the prognostic values and biological roles of the ADAMTS genes in GC.
Highlights
Gastric cancer (GC) is the most common lethal cancer worldwide
By analyzing the A Disintegrin and Metalloproteinase with rombospondins” (ADAMTSs) family of genes, we found that ADAMTS12 and ADAMTS16 had the highest mutation rate (i.e., 12%), which was mainly due to amplification and missense mutation. e lowest rate of genetic change occurred in ADAMTS6
For postprogression survival (PPS) (Figure 8), we found that 14 genes, namely, ADAMTS1 (HR 2.14, P < 0.001), ADAMTS2 (HR 1.66, P < 0.001), ADAMTS3 (HR 1.27, P < 0.001), ADAMTS5 (HR 1.89, P < 0.001), ADAMTS6 (HR 1.97, P < 0.001), ADAMTS7 (HR 1.98, P < 0.001), ADAMTS8 (HR 1.7, P < 0.001), ADAMTS9 (HR 1.42, P < 0.001), ADAMTS12 (HR 1.59, P < 0.001), ADAMTS14 (HR 1.94, P < 0.001), ADAMTS15 (HR 1.43, P < 0.001), ADAMTS17 (HR 1.44, P < 0.001), ADAMTS18 (HR 1.67, P < 0.001), and ADAMTS20 (HR 1.97, P < 0.001), were closely related to PPS. e total survival time of patients with a high expression level of these genes was significantly shorter than that of patients with a low expression level
Summary
Gastric cancer (GC) is the most common lethal cancer worldwide. The techniques used for early screening have improved, and there have been considerable improvements in comprehensive prevention and treatment measures owing to surgical treatment [2, 3], the prognosis of GC remains unsatisfactory [2]. Carcinogenesis is associated with abnormalities in different cellular and intercellular mechanisms such as extracellular matrix (ECM) remodeling. Among all ECM proteases, “A Disintegrin and Metalloproteinase with rombospondins” (ADAMTSs) are a relatively new group and are considered to be associated with carcinogenesis and the local/distant spread of cancer [4]. ADAMTS is a complex extracellular protease related to carcinogenesis and tumor protection.
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