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Neda Nikpoor, David T Tse, Daniel Pelaez; Proteomic profiling of adenoid cystic carcinoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):90.
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to evaluate the effect of intra-arterial cytoreductive chemotherapy on the different cellular compartments of ACC
Biopsy specimens (pre-chemotherapy) and surgical resection specimens (post-chemotherapy) were obtained for 6 patients who underwent intra-arterial cytoreductive chemotherapy for AdCC. Standard techniques were used to deparaffinize and isolate full-length proteins from the specimens. The protein isolates were sent for unbiased high-density phenotypic analysis. Quantitative results were obtained on the normalized amount of each protein present in the paired samples. These results were then confirmed with immunohistochemistry and western blot.
As was expected, the results show that the vast majority of proteins were less prevalent, likely lost due to cytoreductive effects, in the post-chemotherapy specimens. A subset of proteins were present in higher amounts, either upregulated or enriched for, in the post-chemotherapy group. Proteins were clustered based on their putative roles, with several factors related to apoptosis, insulin metabolism, stem cell phenotypes, and survival pathways being differentially expressed due to chemotherapeutic treatment. Of these, fibroblast growth factor receptor 1 (FGFR1) was significantly upregulated in all specimens post-chemotherapy. Immunohistochemistry on paired pre-chemotherapy and post-chemotherapy slides revealed that there were indeed much higher levels of FGFR1 on the cell membrane after cyctoreductive chemotherapy.
When analyzing the results, many proteins were found in higher amounts after cytoreductive chemotherapy. Special attention was paid to proteins with high therapeutic biomarker potential - those known to be found on the cell membrane and for which a drug was already in clinical trials. FGFR1 was significantly upregulated in all specimens and was felt to have the most potential as a neoadjuvant drug target. While limited by the small sample size, this study demonstrates the value of unbiased phenotypic characterization to the understanding of how certain cellular subpopulations can subvert the effects of chemotherapy, and to the identification of potential therapeutic biomarkers.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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