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Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment
Published on: March 25, 2020
A statistical framework for analyzing hypothesized interactions between cells imaged using multispectral microscopy
Chris J Rose1, Khimara Naidoo, Vanessa Clay
1Centre for Imaging Sciences, Institute for Population Health, The University of Manchester, Manchester, United Kingdom. ; The University of Manchester Biomedical Imaging Institute, The University of Manchester, Manchester, United Kingdom. ; Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom.
Insights
Hypothesized Interaction Distribution (HID) analysis quantitatively assesses spatial cell relationships. This method effectively distinguished follicular lymphoma patients with poor versus good survival outcomes.
Area of Science:
- Computational pathology
- Immunohistochemistry analysis
- Spatial biology
Background:
- Multispectral microscopy and multiple staining identify cells with distinct immunohistochemical (IHC) characteristics.
- Hypothesized Interaction Distribution (HID) analysis is introduced for characterizing spatial relationships between cells with specific IHC profiles.
- The method is applied to clinical data for enhanced diagnostic insights.
Purpose of the Study:
- To present and validate the novel HID analysis method.
- To characterize the statistical distribution of pair-wise spatial relationships between cells with particular IHC characteristics.
- To apply HID analysis to clinical data for prognostic assessment.
Main Methods:
- Retrospective analysis of 26 follicular lymphoma patient samples stained for CD20 and YY1.
- Application of HID analysis with leave-one-out validation to group patients.
- Testing the null hypothesis of no difference in Kaplan-Meier survival curves between identified groups.
Main Results:
- Shannon entropy of HIDs significantly differentiated patient groups with distinct survival curves (median survival: 7.70 vs. 110 months, P = 0.00750).
- Specific hypothesized interactions between CD20 and YY1 positive cells were strongly associated with poor survival outcomes.
- HID analysis demonstrated prognostic capability in follicular lymphoma.
Conclusions:
- HID analysis offers quantitative insights into spatial cell interactions based on IHC characteristics.
- The method successfully distinguished between patients with poor and good survival in follicular lymphoma.
- HID analysis holds potential diagnostic and prognostic utility for follicular lymphoma and other diseases.
Background:
Multispectral microscopy and multiple staining can be used to identify cells with distinct immunohistochemical (IHC) characteristics. We present here a method called hypothesized interaction distribution (HID) analysis for characterizing the statistical distribution of pair-wise spatial relationships between cells with particular IHC characteristics and apply it to clinical data.
Materials And Methods:
We retrospectively analyzed data from a study of 26 follicular lymphoma patients in which sections were stained for CD20 and YY1. HID analysis, using leave-one-out validation, was used to assign patients to one of two groups. We tested the null hypothesis of no difference in Kaplan-Meier survival curves between the groups.
Results:
Shannon entropy of HIDs assigned patients to groups that had significantly different survival curves (median survival was 7.70 versus 110 months, P = 0.00750). Hypothesized interactions between pairs of cells positive for both CD20 and YY1 were associated with poor survival.
Conclusions:
HID analysis provides quantitative inferences about possible interactions between spatially proximal cells with particular IHC characteristics. In follicular lymphoma, HID analysis was able to distinguish between patients with poor versus good survival, and it may have diagnostic and prognostic utility in this and other diseases.
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