Open Access

Elevation of ADAM12 facilitates tumor progression by enhancing metastasis and immune infiltration in gastric cancer

  • Authors:
    • Hai Zhu
    • Wen Jiang
    • Haixing Zhu
    • Jinwei Hu
    • Bingge Tang
    • Zhiqiang Zhou
    • Xinyang He
  • View Affiliations

  • Published online on: March 21, 2022     https://doi.org/10.3892/ijo.2022.5341
  • Article Number: 51
  • Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A disintegrin and metalloprotease 12 (ADAM12), an essential transmembrane protein with metalloprotease, cell binding and intracellular signal‑regulating capabilities, has been reported to play a crucial role in various types of cancers. However, the biological function of ADAM12 in gastric cancer (GC) remains unclear. Bioinformatic and experimental analyses were used to determine the expression level and prognostic value of ADAM12 in GC. The level of DNA methylation and the competing endogenous RNA (ceRNA) network was identified using MethSurv, Starbase3.0, miRNet2.0 and experimental analyses. Then, the co‑expression profiles of ADAM12 were determined and subjected to enrichment analysis using the LinkedOmics database. The protein‑protein interaction network and the docking model of ADAM12 were constructed using the GeneMANIA, STRING, and HDOCK webservers. The role of ADAM12 in tumor metastasis and immune infiltration was investigated using in vitro assays and TIMER database exploration. It was found that ADAM12 was overexpressed and was correlated with a poor prognosis of GC patients. In addition, the aberrant DNA methylation status and ceRNA regulation may contribute to the upregulation of ADAM12 in GC. Moreover, the enrichment analysis revealed that ADAM12 is involved in multiple vital biological functions and pathways, such as ‘macrophage activation’, ‘extracellular matrix binding’ and ‘ECM‑receptor interaction’. Subsequently, the protein‑protein interaction network and molecular docking model demonstrated that follistatin like 3 (FSTL3) is a potential binding partner of ADAM12. Finally, it was demonstrated that ADAM12 promotes tumor metastasis, immune infiltration and M2 macrophage polarization in GC. In summary, these results highlight the potential of ADAM12 to be used as a therapeutic target for GC.
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May-2022
Volume 60 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Zhu H, Jiang W, Zhu H, Hu J, Tang B, Zhou Z and He X: Elevation of ADAM12 facilitates tumor progression by enhancing metastasis and immune infiltration in gastric cancer. Int J Oncol 60: 51, 2022
APA
Zhu, H., Jiang, W., Zhu, H., Hu, J., Tang, B., Zhou, Z., & He, X. (2022). Elevation of ADAM12 facilitates tumor progression by enhancing metastasis and immune infiltration in gastric cancer. International Journal of Oncology, 60, 51. https://doi.org/10.3892/ijo.2022.5341
MLA
Zhu, H., Jiang, W., Zhu, H., Hu, J., Tang, B., Zhou, Z., He, X."Elevation of ADAM12 facilitates tumor progression by enhancing metastasis and immune infiltration in gastric cancer". International Journal of Oncology 60.5 (2022): 51.
Chicago
Zhu, H., Jiang, W., Zhu, H., Hu, J., Tang, B., Zhou, Z., He, X."Elevation of ADAM12 facilitates tumor progression by enhancing metastasis and immune infiltration in gastric cancer". International Journal of Oncology 60, no. 5 (2022): 51. https://doi.org/10.3892/ijo.2022.5341