Abstract
BackgroundA disintegrin and metalloprotease 12 (ADAM12) is a member of the multidomain protein family, but the mechanisms by which it affects prognosis and immune cell infiltration in patients with colon adenocarcinoma (COAD) remain unclear. Here, our study aimed to analyze the prognostic value of ADAM12 and investigate the correlation between ADAM12 expression and immune cell infiltration in patients with COAD.MethodsDifferential expression analyses were performed using the Oncomine and UALCAN databases, and prognostic analyses were conducted using PrognoScan, Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan–Meier Plotter. Then, the cBioPortal database was used to analyze alterations in the ADAM12 gene, and the STRING and Metascape websites were used to conduct Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Additionally, relationships between ADAM12 and the immune microenvironment were evaluated based on the TIMER, GEPIA, and TISIDB databases.ResultsADAM12 was overexpressed in COAD tissues, and higher ADAM12 expression correlated with a worse prognosis for patients with COAD. The gene regulatory network suggested that ADAM12 was mainly enriched in extracellular matrix (ECM) organization, ECM proteoglycans, skeletal system development, and ossification, among other pathways. Moreover, ADAM12 expression significantly correlated with the abundance of CD4+ T cells, B cells, CD8+ T cells, neutrophils, macrophages, dendritic cells, and their markers, as well as lymphocytes, immunomodulators, and chemokines.ConclusionsIn colorectal tumors, ADAM12 may play vital roles in regulating the ECM and the recruitment of immune cells, and we suggest that ADAM12 will become a reliable biomarker for determining response to immunotherapy and the prognosis of patients with COAD.
Highlights
According to the latest global cancer survey, colorectal cancer (CRC), a highly heterogeneous disease, is the third most common malignant tumor worldwide [1]
A disintegrin and metalloprotease 12 (ADAM12) mRNA was overexpressed in tumor tissues, such as breast cancer, cervical cancer, CRC, and esophageal cancer
Using the interactive Venn diagram to analyze the difference between the two datasets, our results indicated that ADAM12 expression in colon adenocarcinoma (COAD) was strongly correlated with the Periostin (POSTN), Matrix metallopeptidase 14 (MMP14), Integrin subunit beta 1 (ITGB1), TIMP metallopeptidase inhibitor 2 (TIMP2), and Matrix metallopeptidase 2 (MMP2) genes (Figure 6B)
Summary
According to the latest global cancer survey, colorectal cancer (CRC), a highly heterogeneous disease, is the third most common malignant tumor worldwide [1]. The morbidity and mortality rates of CRC are increasing globally annually, especially in developing countries such as China, Brazil, and India, where CRC-related morbidity and mortality rates are increasing 20% each year [2]. This disease poses a major challenge to global health. A disintegrin and metalloprotease 12 (ADAM12) is a member of the multidomain protein family, but the mechanisms by which it affects prognosis and immune cell infiltration in patients with colon adenocarcinoma (COAD) remain unclear. Our study aimed to analyze the prognostic value of ADAM12 and investigate the correlation between ADAM12 expression and immune cell infiltration in patients with COAD
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