532 Evaluating fibroblast growth factor receptor (FGFR) pathway mRNA expression and protein activation in cholangiocarcinoma tumors
Objectives/Goals: Personalized cancer therapy based on genomic testing is advancing patient care. Genomic alterations in fibroblast growth factor receptor (FGFR) predict response to FGFR inhibitors; however, the role of RNA expression and protein activation is not known. We propose to examine the ph...
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Cambridge University Press
2025-04-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866124011087/type/journal_article |
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| author | Leah Stein Julie W. Reeser Michele R. Wing Eric Samorodnitsky Anoosha Paruchuri Amy Smith Thuy Dao Zachary Risch Emanuel F. Petricoin Sameek Roychowdhury |
| author_facet | Leah Stein Julie W. Reeser Michele R. Wing Eric Samorodnitsky Anoosha Paruchuri Amy Smith Thuy Dao Zachary Risch Emanuel F. Petricoin Sameek Roychowdhury |
| author_sort | Leah Stein |
| collection | DOAJ |
| description | Objectives/Goals: Personalized cancer therapy based on genomic testing is advancing patient care. Genomic alterations in fibroblast growth factor receptor (FGFR) predict response to FGFR inhibitors; however, the role of RNA expression and protein activation is not known. We propose to examine the phospho-proteomic signature in FGFR-altered cancers to identify new candidates for FGFR-targeted therapies. Methods/Study Population: In our preliminary study, we have curated a cohort of FGFR2 mutants (13 FGFR2-fusions and 4 FGFR2 point mutations) with known clinical outcomes to FGFR inhibitors and 8 FGFR2 wild-type (WT) cholangiocarcinoma tumor samples to investigate the phospho-proteomic fingerprint using a clinical grade reverse phase protein array (RPPA). RPPAs are high throughput quantitative antibody-based proteomics assays that can quantify hundreds of proteins in thousands of patient tissues providing a high degree of sensitivity through laser tumor microdissection (LCM). We have selected proteins in the FGFR signaling pathway including FGFR2, AKT, ERK1.2, STAT1/3, FRS2, and PLCg to define the range of phospho-proteomic signal between FGFR2 WT and mutant cancers. All samples will undergo evaluation with RNASeq for gene expression. Results/Anticipated Results: Our initial analysis defined the range of RNA expression of FGFR2 and pFGFR2 protein signal (Y653/654 and Y769) between FGFR2 WT and FGFR2 mutant samples. On average, the FGFR2 mutant cohort displayed higher FGFR2 RNA expression compared to the FGFR2 WT cohort. There is no apparent correlation between RNA expression and clinical response to FGFR-targeted therapy. However, in this small cohort, there is no significant difference in FGFR2 phosphorylation between FGFR2 WT and mutant cancers. RPPA analysis of FGFR downstream signaling proteins reveals a wide range of phosphorylation, but no significant difference between FGFR2 WT and mutant cancers. Discussion/Significance of Impact: These findings illustrate the complexities of FGFR signaling between FGFR2 WT and mutant cancers. These data suggest that tumors with genomically WT FGFR may display increased pFGFR2 and downstream signaling phospho-proteins. We propose a larger study of cholangiocarcinoma to evaluate evidence of FGFR pathway activation in WT tumors. |
| format | Article |
| id | doaj-art-325a61adc9b4497e80bbade277ed6f14 |
| institution | DOAJ |
| issn | 2059-8661 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj-art-325a61adc9b4497e80bbade277ed6f142025-08-20T02:40:51ZengCambridge University PressJournal of Clinical and Translational Science2059-86612025-04-01915515610.1017/cts.2024.1108532 Evaluating fibroblast growth factor receptor (FGFR) pathway mRNA expression and protein activation in cholangiocarcinoma tumorsLeah Stein0Julie W. Reeser1Michele R. Wing2Eric Samorodnitsky3Anoosha Paruchuri4Amy Smith5Thuy Dao6Zachary Risch7Emanuel F. Petricoin8Sameek Roychowdhury9The Ohio State UniversityThe Ohio State University Wexner Medical Center and James Cancer HospitalThe Ohio State University Wexner Medical Center and James Cancer HospitalThe Ohio State University Wexner Medical Center and James Cancer HospitalThe Ohio State University Wexner Medical Center and James Cancer HospitalThe Ohio State University Wexner Medical Center and James Cancer HospitalThe Ohio State University Wexner Medical Center and James Cancer HospitalThe Ohio State University Wexner Medical Center and James Cancer HospitalCenter for Applied Proteomics and Molecular Medicine, George Mason UniversityThe Ohio State University Wexner Medical Center and James Cancer HospitalObjectives/Goals: Personalized cancer therapy based on genomic testing is advancing patient care. Genomic alterations in fibroblast growth factor receptor (FGFR) predict response to FGFR inhibitors; however, the role of RNA expression and protein activation is not known. We propose to examine the phospho-proteomic signature in FGFR-altered cancers to identify new candidates for FGFR-targeted therapies. Methods/Study Population: In our preliminary study, we have curated a cohort of FGFR2 mutants (13 FGFR2-fusions and 4 FGFR2 point mutations) with known clinical outcomes to FGFR inhibitors and 8 FGFR2 wild-type (WT) cholangiocarcinoma tumor samples to investigate the phospho-proteomic fingerprint using a clinical grade reverse phase protein array (RPPA). RPPAs are high throughput quantitative antibody-based proteomics assays that can quantify hundreds of proteins in thousands of patient tissues providing a high degree of sensitivity through laser tumor microdissection (LCM). We have selected proteins in the FGFR signaling pathway including FGFR2, AKT, ERK1.2, STAT1/3, FRS2, and PLCg to define the range of phospho-proteomic signal between FGFR2 WT and mutant cancers. All samples will undergo evaluation with RNASeq for gene expression. Results/Anticipated Results: Our initial analysis defined the range of RNA expression of FGFR2 and pFGFR2 protein signal (Y653/654 and Y769) between FGFR2 WT and FGFR2 mutant samples. On average, the FGFR2 mutant cohort displayed higher FGFR2 RNA expression compared to the FGFR2 WT cohort. There is no apparent correlation between RNA expression and clinical response to FGFR-targeted therapy. However, in this small cohort, there is no significant difference in FGFR2 phosphorylation between FGFR2 WT and mutant cancers. RPPA analysis of FGFR downstream signaling proteins reveals a wide range of phosphorylation, but no significant difference between FGFR2 WT and mutant cancers. Discussion/Significance of Impact: These findings illustrate the complexities of FGFR signaling between FGFR2 WT and mutant cancers. These data suggest that tumors with genomically WT FGFR may display increased pFGFR2 and downstream signaling phospho-proteins. We propose a larger study of cholangiocarcinoma to evaluate evidence of FGFR pathway activation in WT tumors.https://www.cambridge.org/core/product/identifier/S2059866124011087/type/journal_article |
| spellingShingle | Leah Stein Julie W. Reeser Michele R. Wing Eric Samorodnitsky Anoosha Paruchuri Amy Smith Thuy Dao Zachary Risch Emanuel F. Petricoin Sameek Roychowdhury 532 Evaluating fibroblast growth factor receptor (FGFR) pathway mRNA expression and protein activation in cholangiocarcinoma tumors Journal of Clinical and Translational Science |
| title | 532 Evaluating fibroblast growth factor receptor (FGFR) pathway mRNA expression and protein activation in cholangiocarcinoma tumors |
| title_full | 532 Evaluating fibroblast growth factor receptor (FGFR) pathway mRNA expression and protein activation in cholangiocarcinoma tumors |
| title_fullStr | 532 Evaluating fibroblast growth factor receptor (FGFR) pathway mRNA expression and protein activation in cholangiocarcinoma tumors |
| title_full_unstemmed | 532 Evaluating fibroblast growth factor receptor (FGFR) pathway mRNA expression and protein activation in cholangiocarcinoma tumors |
| title_short | 532 Evaluating fibroblast growth factor receptor (FGFR) pathway mRNA expression and protein activation in cholangiocarcinoma tumors |
| title_sort | 532 evaluating fibroblast growth factor receptor fgfr pathway mrna expression and protein activation in cholangiocarcinoma tumors |
| url | https://www.cambridge.org/core/product/identifier/S2059866124011087/type/journal_article |
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