A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines
2.2. Clonogenicity Test for the Response to Ionizing Radiation by Determining the SF2 Parameter
2.3. RNA Extraction from Cells
2.4. cDNA Microarrays
2.5. Transcriptome Analysis
2.6. Patient Cohort
2.7. Statistical Packages and Analysis
2.8. Obtaining Gene Signatures
3. Results
3.1. Survival Values at 2 Gy and Survival Curves of All Cell Lines
3.2. Identification of Genes with Differential Expression between Radiosensitive and Radioresistant Lines
3.3. Individual Validation of Genes with Differential Expression as Prognostic Biomarkers in the TCGA Cohort of Radiation-Treated Patients
3.4. Obtaining the Prognostic Signature
3.5. Individual Validation of Genes with Differential Expression between Radiosensitive and Radioresistant Lines as a Predictive Biomarker of Response in the TCGA Cohort of Interest
3.6. Generation of a Common Gene Signature for Global Survival Prediction and Progression-Free Survival
3.7. Application of the Gene Signature for Prediction of OS and PFS Depending on the Histological Subtype
3.8. Univariate and Multivariate Analysis of Clinical and Pathological Variables, Their Impact on Overall Survival and PFS and Their Influence on the Proposed Gene Signature
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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Cell Line | SF2 | SD |
---|---|---|
Radioresistant | ||
H1975 | 0.891 | 0.0104 |
A549 | 0.832 | 0.162 |
HC827 | 0.745 | 0.2 |
H358 | 0.676 | - |
H2228 | 0.646 | 0.056 |
H3122 | 0.622 | 0.056 |
H460 | 0.617 | 0.129 |
H1650 | 0.570 | 0.156 |
Radiosensitive | ||
Calu1 | 0.454 | 0.079 |
H520 | 0.490 | - |
H1437 | 0.448 | - |
H226 | 0.430 | 0.09 |
Calu3 | 0.325 | 0.131 |
H2009 | 0.228 | 0.024 |
H1781 | 0.180 | 0.067 |
Variables | Beta | ET | Wald | HR | 95% CI for HR | p-Value | |
---|---|---|---|---|---|---|---|
Inferior | Superior | ||||||
Age at diagnosis | −0.25 | 0.27 | 0.88 | 0.78 | 0.46 | 1.32 | 0.35 |
Year of diagnosis | 0.46 | 0.31 | 2.28 | 1.59 | 0.87 | 2.91 | 0.13 |
Sex | −0.21 | 0.27 | 0.65 | 0.81 | 0.48 | 1.36 | 0.42 |
Histological subtype | 0.38 | 0.27 | 1.97 | 1.46 | 0.86 | 2.48 | 0.16 |
T component | −0.38 | 0.29 | 1.71 | 0.68 | 0.39 | 1.21 | 0.19 |
Nodal load | −0.24 | 0.27 | 0.80 | 0.78 | 0.46 | 1.34 | 0.37 |
Tumoral stage (AJCC) | −0.52 | 0.27 | 3.73 | 0.60 | 0.35 | 1.01 | 0.05 |
Genetic signature OS | 1.10 | 0.28 | 15.16 | 2.99 | 1.72 | 5.19 | <0.0001 |
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Peinado-Serrano, J.; Quintanal-Villalonga, Á.; Muñoz-Galvan, S.; Verdugo-Sivianes, E.M.; Mateos, J.C.; Ortiz-Gordillo, M.J.; Carnero, A. A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung Cancer. Cancers 2022, 14, 2054. https://doi.org/10.3390/cancers14092054
Peinado-Serrano J, Quintanal-Villalonga Á, Muñoz-Galvan S, Verdugo-Sivianes EM, Mateos JC, Ortiz-Gordillo MJ, Carnero A. A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung Cancer. Cancers. 2022; 14(9):2054. https://doi.org/10.3390/cancers14092054
Chicago/Turabian StylePeinado-Serrano, Javier, Álvaro Quintanal-Villalonga, Sandra Muñoz-Galvan, Eva M. Verdugo-Sivianes, Juan C. Mateos, María J. Ortiz-Gordillo, and Amancio Carnero. 2022. "A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung Cancer" Cancers 14, no. 9: 2054. https://doi.org/10.3390/cancers14092054