Abstract 4301: ADAM9 plays a key role in the aggressive behavior of triple negative breast carcinoma and represents a potential treatment target
Authors: Zhou Rui , Cho William CS , Ma Victor WS , Cheuk Wah , Yik-ka So Grace , Wong SC Cesar , Chan Lawrence WC 
Published: September 2020

Introduction: A Disintegrin and Metalloproteinase 9 (ADAM9) promotes cancer progression via its metalloproteinase and disintegrin domains, and upregulated ADAM9 is found in pancreatic, prostate and breast carcinomas. The expression of ADAM9 in triple negative breast carcinoma (TNBC), however, is still unclear. We investigated the expression of ADAM9 in TNBC, its role in tumor progression and prognostic implication in TNBC patients.

Materials and Methods: The expression of ADAM9 was investigated in TNBC and non-TNBC cell lines as well as TNBC and non-TNBC tumor tissues. ADAM9 mRNA expression data in TNBC cell lines (n = 14) and non-TNBC cell lines (n = 11) were obtained from Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo/) database. A total of 24 TNBC and 20 non-TNBC breast tumor specimens were also collected. The Kaplan-Meier (KM) plotter was used to investigate the association between ADAM9 expression level and survival in TNBC patients. Cell proliferation, migration and invasion assays were performed to investigate the role of ADAM9 in TNBC cell line (MDA-MB-231).

Results: ADAM9 mRNA expression in TNBC cell lines was significantly higher than that of non-TNBC cell lines (p = 0.038). Strong staining of ADAM9 was detected in primary tumor tissues from TNBC patients, but only weak staining was found in primary non-TNBC tumors. Statistical analysis showed that the ADAM9 staining intensity (p &lt; 0.05) and expression level (p &lt; 0.05) were markedly increased in TNBC group compared with the non-TNBC group. High level of ADAM9 mRNA expression was associated with poorer overall survival (p &lt; 0.01), more distant metastasis-free survival (p &lt; 0.01) and shorter relapse-free survival (RFS) (p &lt; 0.001). Furthermore, high ADAM9 mRNA level was also significantly associated with poor RFS in TNBC (p &lt; 0.01). ADAM9 mRNA expression level was associated with RFS in grade II and III tumors, but not in grade I tumors (p = 0.21). An increased hazard ratio was also found with grade II tumors (p = 0.2) and grade III tumors (p = 0.003). Scrambled siRNA with green fluorescent protein was transfected in MDA-MB-231 cells by lipofectamine 2000. ADAM9 protein and mRNA expression were successfully inhibited in these transfected MDA-MB-231 cells, which lead to suppression in cell proliferation, migration and invasion on functional assays.

Conclusion: Our results showed the ADAM9 was overexpressed in TNBC and was associated with poor prognosis in TNBC patients. ADAM9 was found to play a key role and may represent a potential treatment target because inhibition of ADAM9 mRNA and protein expression was associated with suppression of cell proliferation, migration and invasion in TNBC cell line.

Keywords: ADAM9, Prognosis, Triple negative breast cancer

Citation Format: Rui Zhou, William CS Cho, Victor WS Ma, Wah Cheuk, Grace Yik-ka So, SC Cesar Wong, Lawrence WC Chan. ADAM9 plays a key role in the aggressive behavior of triple negative breast carcinoma and represents a potential treatment target [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4301.