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Multiplex Proximity Ligation Assay to Identify Potential Prognostic Biomarkers for Improved Survival in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy
- Source :
- Int J Radiat Oncol Biol Phys
- Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Oncology
Male
Cancer Research
medicine.medical_specialty
CA-19-9 Antigen
medicine.medical_treatment
Context (language use)
PDGFRA
Radiosurgery
Article
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Biomarkers, Tumor
Humans
Radiology, Nuclear Medicine and imaging
Mesothelin
Proportional Hazards Models
Chemotherapy
Radiation
biology
Performance status
Proportional hazards model
business.industry
Interleukin-8
Nucleic acid amplification technique
Prognosis
Surgery
Pancreatic Neoplasms
030104 developmental biology
030220 oncology & carcinogenesis
biology.protein
Female
Matrix Metalloproteinase 1
business
Nucleic Acid Amplification Techniques
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Int J Radiat Oncol Biol Phys
- Accession number :
- edsair.doi.dedup.....3f44e7225170105f3120198cb4f7d0e5