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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

3621 - Predicting survival benefit of capecitabine plus cisplatin in patients with metastatic gastric cancer patients using quantitative proteomics.

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Dongyao Yan

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

D. Yan1, M. Ryu2, E. An1, Y.S. Park3, H. Na2, J. Ma4, Y. Tian1, F. Cecchi1, T. Hembrough1, Y. Kang4

Author affiliations

  • 1 R&d, NantOmics, LLC, 20850 - Rockville/US
  • 2 Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 05505 - Seoul/KR
  • 3 Department Of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 05505 - Seoul/KR
  • 4 Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR
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Resources

Abstract 3621

Background

Capecitabine plus cisplatin (XP) is a standard treatment for metastatic gastric cancer (mGC). Capecitabine activation requires the enzymes uridine-cytidine kinase 2 (UCK2) and orotate phosphoribosyl transferase (OPRT). We previously used mass spectrometry to quantitate UCK2 in tumor samples from 5-FU-treated patients with stage II/III colorectal cancer; UCK2 protein expression > 319 amol/ug of tumor protein was associated with improved survival. Here, we assessed whether these biomarkers would predict survival among mGC patients treated with XP.

Methods

Archived tumor samples from patients with mGC were microdissected and solubilized for mass spectrometric quantitation of 16 protein biomarkers. Kaplan-Meier survival curves were compared using a log-rank test. Multivariate Cox models of survival included clinical covariates and protein biomarkers.

Results

mGC tumor samples from 116 XP-treated patients were analyzed (males: 64%; median age: 55 years). All samples expressed OPRT protein (range: 202 – 1719 amol/ug), and 114 of 116 expressed UCK2 (range: 119 – 933 amol/ug). Patients with UCK2 expression above the pre-defined cutoff of 319 amol/μg (n = 30) had longer time to progression (TTP) (HR: 0.60; p = 0.020) than patients below the cutoff. Results for overall survival (OS) were similar (HR: 0.59; p = 0.015). OPRT protein expression > 790 amol/ug (n = 24) was associated with longer TTP (HR: 0.58; p = 0.019) and longer OS (HR: 0.60; p = 0.029). In multivariate analysis, UCK2 and OPRT remained independent predictors of survival after adjustment for age, gender, ECOG performance status, metastatic sites, and other clinical covariates.

Conclusions

We validated a pre-defined UCK2 expression cutoff and discovered an OPRT cutoff in an XP-treated mGC patient cohort. Patients with tumor expression of UCK2 and OPRT proteins above quantified thresholds survived longer than patients with lower expression. Mass spectrometric quantitation of these common tumor proteins at diagnosis may improve patient selection for XP. Studies to validate these and other chemopredictive biomarkers are ongoing.

Clinical trial identification

Legal entity responsible for the study

NantOmics.

Funding

NantOmics.

Editorial Acknowledgement

Disclosure

D. Yan, E. An, Y. Tian, F. Cecchi, T. Hembrough: Employment: NantOmics. All other authors have declared no conflicts of interest.

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