Abstract 490P
Background
A disintegrin and metalloprotease (ADAM) family is a widely expressed protease that has been implicated in pathological condition. ADAM15, a catalytically active member of ADAM family, is upregulated in multiple tumors including breast, lung, prostate and liver. ADAM15 play a critical role in tumor progression, it enhances the expression of pro-angiogenic genes and potentiates integrin binding and inflammation, thus regulating cell adhesion and migration. However, the role of ADAM15 in the tumor prediction, immunity and therapy is still elusive.
Methods
By combining results of multiple databases, the presence of ADAM15 was examined in pan-caner. Immunohistochemistry was obtained from Human Protein Atlas (HPA) database in particular tumor tissues. Tumor Immune Estimation Resource (TIMER) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm were utilized to analyze the immune infiltration and immune checkpoint genes associated with ADAM15. The impact on ADAM15 was explored using TISMO. Finally, drug sensitivity analysis and following molecular docking were conducted to assess potential sensitivity compounds. Validation was performed using with reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC).
Results
Both mRNA and protein of ADAM15 are highly expressed in different types of cancer, validated by IHC and RT-PCR. Moreover, high ADAM15 expression is associated with poor prognosis and could be noted as a novel biomarker for outstanding diagnostic performance. From the perspective of tumor microenvironment (TME), ADAM15 related with cancer immune regulation. Drug sensitivity analysis revealed a positive correlation and significant change of gene with AZD-8055 and Nitazoxanide, negative correlation with Oxaliplatin and Ponatinib, which was confirmed by molecular docking.
Conclusions
ADAM15 may exert a significant influence on cancer development, prognosis, and susceptibility to therapy. In addition, it may serve as a potential prognostic and immunological pan-cancer biomarker.
Clinical trial identification
Editorial acknowledgement
We acknowledge all the patients who offered the tissue specimens.
Legal entity responsible for the study
The authors.
Funding
Key Discipline Construction Project Pudong Health Bureau of Shanghai (PWZxk2022-02), Scientific Research Project of Pudong New Area Science and Economic Commission (PKJ2022-Y18), Academic Leaders Training Program of Pudong Health Bureau of Shanghai (PWRd2022-05).
Disclosure
All authors have declared no conflicts of interest.