TY - JOUR
T1 - Multiplex Proximity Ligation Assay to Identify Potential Prognostic Biomarkers for Improved Survival in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy
AU - Rao, Avani D.
AU - Liu, Yufei
AU - von Eyben, Rie
AU - Hsu, Charles C.
AU - Hu, Chen
AU - Rosati, Lauren M.
AU - Parekh, Arti
AU - Ng, Kendall
AU - Hacker-Prietz, Amy
AU - Zheng, Lei
AU - Pawlik, Timothy M.
AU - Laheru, Daniel A.
AU - Jaffee, Elizabeth M.
AU - Weiss, Matthew J
AU - Le, Dung T.
AU - Hruban, Ralph H.
AU - De Jesus-Acosta, Ana
AU - Wolfgang, Christopher L.
AU - Narang, Amol K.
AU - Chang, Daniel T.
AU - Koong, Albert C.
AU - Herman, Joseph
N1 - Funding Information:
J.H. is supported by the Claudio X. Gonzalez Family Foundation, Flannery Family Foundation, Alexander Family Foundation, Keeling Family Foundation, DeSanti Family Foundation, Viragh Family Foundation, and the McKnight Family Foundation. R.H. is supported by The Sol Goldman Pancreatic Cancer Research Center and National Institutes of Health Specialized Programs of Research Excellence grant CA62924. A.K. is supported by the My Blue Dots Fund. Y.L. is supported by the Stanford University Medical Scholars Research Program.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Purpose: To explore seromarker levels for associations with outcomes in locally advanced pancreatic cancer (LAPC) patients who received chemotherapy and stereotactic body radiation therapy (SBRT). Methods and Materials: Serum from LAPC patients in 2 prospective trials of hypofractionated SBRT (5-6.6 Gy × 5) was collected before SBRT. Proximity ligation assay quantified the expression levels of 36 pancreatic cancer–specific candidate seromarkers: Axl, BMP2, CA 125, CA 19-9, CEA, CXCL-1/6/9/10, EGFR, Gas6, Her2, IGF-2, IGFBP-2/3/7, IL-6/6Ra/7/8/12, mesothelin, MMP-1/2/3/7, osteopontin, PDGFRa, PDK1, PF4, RegIV, SPARC, TGF-β, VEGF-A/D, and YKL40. Seromarker values were log transformed owing to log-normal distribution of the values, and Cox regression analysis was performed to assess for any association with overall survival. The Benjamini-Hochberg method was used to control for a false discovery rate (FDR) of only 10%. Results: Sixty-four patients with LAPC were included. No clinical factors (including surgical resection, receipt of pre-SBRT chemotherapy, receipt of post-SBRT chemotherapy, performance status, and age) or potential biomarkers in the panel were associated with improved survival in this cohort after application of the FDR correction. Potential prognostic factors for improved survival for future investigation included surgical resection (P=.007, adjusted P=.153) and the serum expression of IL-8 (P=.006, adjusted P=.153), CA 19-9 (P=.031, adjusted P=.377), and MMP-1 (P=.036, adjusted P=.377). Conclusions: These data explore the expression of a panel of proteins in pre-SBRT serum of LAPC patients in the context of a conservative FDR correction. None of the clinical factors or expression levels of the serum proteins were found to be associated with survival; however, IL-8, CA 19-9, and MMP-1 were highlighted as possible candidates warranting inclusion in future seromarker studies in the ongoing efforts to identify tools for risk stratification and treatment allocation in LAPC.
AB - Purpose: To explore seromarker levels for associations with outcomes in locally advanced pancreatic cancer (LAPC) patients who received chemotherapy and stereotactic body radiation therapy (SBRT). Methods and Materials: Serum from LAPC patients in 2 prospective trials of hypofractionated SBRT (5-6.6 Gy × 5) was collected before SBRT. Proximity ligation assay quantified the expression levels of 36 pancreatic cancer–specific candidate seromarkers: Axl, BMP2, CA 125, CA 19-9, CEA, CXCL-1/6/9/10, EGFR, Gas6, Her2, IGF-2, IGFBP-2/3/7, IL-6/6Ra/7/8/12, mesothelin, MMP-1/2/3/7, osteopontin, PDGFRa, PDK1, PF4, RegIV, SPARC, TGF-β, VEGF-A/D, and YKL40. Seromarker values were log transformed owing to log-normal distribution of the values, and Cox regression analysis was performed to assess for any association with overall survival. The Benjamini-Hochberg method was used to control for a false discovery rate (FDR) of only 10%. Results: Sixty-four patients with LAPC were included. No clinical factors (including surgical resection, receipt of pre-SBRT chemotherapy, receipt of post-SBRT chemotherapy, performance status, and age) or potential biomarkers in the panel were associated with improved survival in this cohort after application of the FDR correction. Potential prognostic factors for improved survival for future investigation included surgical resection (P=.007, adjusted P=.153) and the serum expression of IL-8 (P=.006, adjusted P=.153), CA 19-9 (P=.031, adjusted P=.377), and MMP-1 (P=.036, adjusted P=.377). Conclusions: These data explore the expression of a panel of proteins in pre-SBRT serum of LAPC patients in the context of a conservative FDR correction. None of the clinical factors or expression levels of the serum proteins were found to be associated with survival; however, IL-8, CA 19-9, and MMP-1 were highlighted as possible candidates warranting inclusion in future seromarker studies in the ongoing efforts to identify tools for risk stratification and treatment allocation in LAPC.
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U2 - 10.1016/j.ijrobp.2017.10.001
DO - 10.1016/j.ijrobp.2017.10.001
M3 - Article
C2 - 29157747
AN - SCOPUS:85034113213
SN - 0360-3016
VL - 100
SP - 486
EP - 489
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -