Development of a Single Molecule Counting Assay to Differentiate Chromophobe Renal Cancer and Oncocytoma in Clinics
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Human Subjects and Study Design
2.2. Coring, RNA Extraction, and Quality Control
2.3. Quantification of Gene Expression Data
2.4. Discovery Data, Train-Validation-Test Set, Supervised Models
2.5. Statistical Methods
3. Results
3.1. Human Subject Demographics
3.2. Univariate Analysis
3.3. Unsupervised and Supervised Machine Learning Models
3.4. H&E Scoring between Pathologists
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | chRCC a | RO b | Overall | p-Value |
---|---|---|---|---|
Stage, n(%) | ||||
1 | 11(64.7%) | NA | 11(34.4%) | |
2 | 3(17.6%) | NA | 3(9.4%) | |
3 | 3(17.6%) | NA | 3(9.4%) | |
Age at Diagnosis, Mean (SD) | 57.8(14.7) | 71.5(8.51) | 64.3(13.9) | 0.003 * |
Race, n (%) | 0.55 ** | |||
AA | 5(29.4%) | 5(33.3%) | 10(31.3%) | |
C | 12(70.6%) | 9(60%) | 21(65.6%) | |
Other | 0 | 1(6.7%) | 1(3.1%) | |
Gender, n (%) | 0.11** | |||
F | 8(47.1%) | 3(20%) | 11(34.4%) | |
M | 9(52.9%) | 12(80%) | 21(65.6) | |
Tumor size (mean) | 5.15(2.4) | 4.68(4.05) | 4.93(3.22) | 0.696 ** |
Gene | Optimal Cut Point | Accuracy | AUC | Sensitivity | Specificity |
---|---|---|---|---|---|
AP1M2 | 10.16 | 0.97 | 0.96 | 0.94 | 1 |
AQP6 | 13.24 | 1 | 1 | 1 | 1 |
ATP2C1 | 11.38 | 0.87 | 0.94 | 0.94 | 0.79 |
BSPRY | 9.2 | 0.97 | 0.99 | 1 | 0.93 |
CLDN8 | 12.57 | 0.93 | 0.93 | 0.94 | 0.93 |
DNAI3 | 6.51 | 0.9 | 0.93 | 0.86 | 0.94 |
ELMO3 | 9.32 | 0.97 | 0.97 | 1 | 0.93 |
ESRP1 | 9.94 | 0.97 | 0.99 | 1 | 0.93 |
HOOK2 | 9.02 | 0.97 | 0.99 | 1 | 0.93 |
ITGB3 | 9.97 | 0.97 | 0.98 | 0.93 | 1 |
KCNG3 | 7.62 | 0.8 | 0.83 | 0.86 | 0.75 |
KIDINS220 | 9.8 | 0.9 | 0.92 | 0.93 | 0.88 |
KRT7 | 8.28 | 0.9 | 0.96 | 0.94 | 0.86 |
LAMA1 | 5.63 | 0.6 | 0.5 | 0.36 | 0.81 |
LIMS1 | 9.26 | 0.97 | 0.98 | 1 | 0.94 |
LRFN5 | 9.55 | 0.8 | 0.88 | 0.63 | 1 |
LSR | 10.43 | 0.93 | 0.96 | 0.88 | 1 |
MANEA | 8.66 | 0.9 | 0.9 | 0.86 | 0.94 |
MAP4K3 | 8.62 | 0.93 | 0.98 | 1 | 0.88 |
MSH2 | 8.37 | 0.67 | 0.54 | 0.86 | 0.5 |
NDUFS1 | 11.33 | 0.9 | 0.91 | 1 | 0.81 |
PLCL1 | 10.78 | 0.87 | 0.9 | 0.93 | 0.81 |
PLCL2 | 11.18 | 0.73 | 0.75 | 0.56 | 0.93 |
PNPT1 | 8.68 | 0.87 | 0.82 | 0.86 | 0.88 |
PRDX3 | 11.94 | 0.97 | 0.96 | 1 | 0.94 |
RSPO3 | 8.83 | 0.83 | 0.88 | 0.69 | 1 |
S100A1 | 7.12 | 0.87 | 0.88 | 0.93 | 0.81 |
SOCS1 | 9.32 | 0.93 | 0.98 | 0.94 | 0.93 |
SPINT2 | 13 | 0.97 | 0.99 | 0.94 | 1 |
SUCLA2 | 10.83 | 0.87 | 0.85 | 0.86 | 0.88 |
Metric | Random Forest | SVM | GLM | Supervised UMAP |
---|---|---|---|---|
Sensitivity | 0.84 | 0.76 | 0.88 | 1 |
Specificity | 1 | 1 | 1 | 1 |
Accuracy | 0.93 | 0.83 | 0.9 | 1 |
95% CI | 0.78–0.99 | 0.65–0.94 | 0.73–0.98 | - |
p-value | 4.74 × 10−5 | 0.07659 | 0.001066 | 0 |
PPV | 1 | 1 | 1 | 1 |
NPV | 0.87 | 0.64 | 0.78 | 1 |
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Bin Satter, K.; Ramsey, Z.; Tran, P.M.H.; Hopkins, D.; Bearden, G.; Richardson, K.P.; Terris, M.K.; Savage, N.M.; Kavuri, S.K.; Purohit, S. Development of a Single Molecule Counting Assay to Differentiate Chromophobe Renal Cancer and Oncocytoma in Clinics. Cancers 2022, 14, 3242. https://doi.org/10.3390/cancers14133242
Bin Satter K, Ramsey Z, Tran PMH, Hopkins D, Bearden G, Richardson KP, Terris MK, Savage NM, Kavuri SK, Purohit S. Development of a Single Molecule Counting Assay to Differentiate Chromophobe Renal Cancer and Oncocytoma in Clinics. Cancers. 2022; 14(13):3242. https://doi.org/10.3390/cancers14133242
Chicago/Turabian StyleBin Satter, Khaled, Zach Ramsey, Paul M. H. Tran, Diane Hopkins, Gregory Bearden, Katherine P. Richardson, Martha K. Terris, Natasha M. Savage, Sravan K. Kavuri, and Sharad Purohit. 2022. "Development of a Single Molecule Counting Assay to Differentiate Chromophobe Renal Cancer and Oncocytoma in Clinics" Cancers 14, no. 13: 3242. https://doi.org/10.3390/cancers14133242