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IHC-based subcellular quantification provides new insights into prognostic relevance of FLIP and procaspase-8 in non-small-cell lung cancer
- Source :
- Cell Death Discovery, Hutchinson, R A, Coleman, H G, Gately, K, Young, V, Nicholson, S, Cummins, R, Kay, E, Hynes, S O, Dunne, P D, Senevirathne, S, Hamilton, P W, McArt, D G & Longley, D B 2017, ' IHC-based subcellular quantification provides new insights into prognostic relevance of FLIP and procaspase-8 in non-small-cell lung cancer ', Cell death discovery, vol. 3, 17050 . https://doi.org/10.1038/cddiscovery.2017.50
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- In this study, we developed an image analysis algorithm for quantification of two potential apoptotic biomarkers in non-small-cell lung cancer (NSCLC): FLIP and procaspase-8. Immunohistochemical expression of FLIP and procaspase-8 in 184 NSCLC tumors were assessed. Individual patient cores were segmented and classified as tumor and stroma using the Definiens Tissue Studio. Subsequently, chromogenic expression of each biomarker was measured separately in the nucleus and cytoplasm and reported as a quantitative histological score. The software package pROC was applied to define biomarker thresholds. Cox proportional hazards analysis was applied to generate hazard ratios (HRs) and associated 95% CI for survival. High cytoplasmic expression of tumoral (but not stromal) FLIP was associated with a 2.5-fold increased risk of death in lung adenocarcinoma patients, even when adjusted for known confounders (HR 2.47, 95% CI 1.14–5.35). Neither nuclear nor cytoplasmic tumoral procaspase-8 expression was associated with overall survival in lung adenocarcinoma patients; however, there was a significant trend (P for trend=0.03) for patients with adenocarcinomas with both high cytoplasmic FLIP and high cytoplasmic procaspase-8 to have a multiplicative increased risk of death. Notably, high stromal nuclear procaspase-8 expression was associated with a reduced risk of death in lung adenocarcinoma patients (adjusted HR 0.31, 95% CI 0.15–0.66). On further examination, the cells with high nuclear procaspase-8 were found to be of lymphoid origin, suggesting that the better prognosis of patients with tumors with high stromal nuclear procaspase-8 is related to immune infiltration, a known favorable prognostic factor. No significant associations were detected in analysis of lung squamous cell carcinoma patients. Our results suggest that cytoplasmic expression of FLIP in the tumor and nuclear expression of procaspase-8 in the stroma are prognostically relevant in non-small-cell adenocarcinomas but not in squamous cell carcinomas of the lung.
- Subjects :
- 0301 basic medicine
Cancer Research
Pathology
medicine.medical_specialty
Stromal cell
Immunology
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
SDG 3 - Good Health and Well-being
Stroma
Journal Article
Medicine
Lung cancer
business.industry
Proportional hazards model
Cell Biology
medicine.disease
030104 developmental biology
Flip
030220 oncology & carcinogenesis
Immunohistochemistry
Adenocarcinoma
Biomarker (medicine)
business
Subjects
Details
- ISSN :
- 20587716
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- Cell Death Discovery
- Accession number :
- edsair.doi.dedup.....ce25771d4dacdbef5d4a82afa9ef86d6