High Density of NRF2 Expression in Malignant Cells Is Associated with Increased Risk of CNS Metastasis in Early-Stage NSCLC
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Survival Analysis
2.3. Risk of Relapse: Univariate Analyses and Chi-Square Test
2.4. Multivariate CNS Metastasis Risk Analysis in the Whole-Tissue Core Compartment
3. Discussion
4. Materials and Methods
4.1. Patient Population
4.2. Multiplex Immunofluorescence Staining and Scanning
4.3. Image Analysis: Cell Segmentation and Fluorescence Intensity Measurements
4.4. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variable | Frequency |
---|---|
Gender (% male) | 50 [152/304] |
Age (mean ± SD) | 67.5 ± 7.6 |
Histology (%) Adenocarcinoma Squamous cell Large cell Adenosquamous NOS/mixed type | 57.6 [175/304] 29.9 [91/304] 8.2 [25/304] 3 [9/304] 1.4 [4/304] |
Stage at diagnosis IA IB IIA IIB IIIA IIIB | 38.8 [118/304] 22.7 [69/304] 10.5 [32/304] 10.2 [31/304] 14.5 [44/304] 3.3 [10/304] |
Smoking status (%) Current Ex-smoker (>1 year) Never smoked | 51.6 [157/304] 36.5 [111/304] 11.8 [36/304] |
Relapse site (%) No relapse CNS Thoracic cavity Bone Liver Adrenal Multiple organs | 56.6 [146/258] 6.2 [16/258] 22.9 [59/258] 4.6 [12/258] 1.9 [5/258] 0.4 [1/258] 7.4 [19/258] |
NRF2 in cancer cells, + vs. − (%) | 50 [152/304] |
Variable | Non-CNS Relapse/Relapse Free | CNS Relapse | Total Row | |
---|---|---|---|---|
NRF2+/CK+ cell density | Low | 124 | 2 | 126 |
High | 118 | 14 | 132 | |
Total column | 242 | 16 | 258 |
Univariate Analysis | Odds Ratio (95%CI) | p–Value |
---|---|---|
NRF2 (+ vs. −) | 7.36 (1.64–33.06) | 0.009 |
Sex (female vs. male) | 0.79 (0.29–2.19) | 0.652 |
Age * | 0.96 (0.90–1.02) | 0.198 |
Histology (adenocarcinoma vs. rest) | 1.02 (0.37–2.81) | 0.997 |
Stage IA IB IIA IIB IIIA IIIB | Ref 2.56 (0.69–9.45) 2.15 (0.37–12.47) 1.08 (0.12–10.09) 2.18 (0.47–10.26) – | Ref 0.158 0.393 0.949 0.322 0.999 |
Multivariate analysis | ||
NRF2 (+ vs. −) | 8.00 (1.70–37.60) | 0.009 |
Age * | 0.95 (0.88–1.01) | 0.106 |
Histology (adenocarcinoma vs. rest) | 1.08 (0.36–3.26) | 0.891 |
Stage IA IB IIA IIB IIIA IIIB | Ref 2.43 (0.60–9.84) 3.19 (0.47–21.59) 0.92 (0.09–9.12) 1.36 (0.28–6.68) – | Ref 0.212 0.234 0.941 0.706 0.999 |
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Tsakonas, G.; Martín-Bernabé, A.; Rounis, K.; Moreno-Ruiz, P.; Botling, J.; De Petris, L.; Ylipää, A.; Mezheyeuski, A.; Micke, P.; Östman, A.; et al. High Density of NRF2 Expression in Malignant Cells Is Associated with Increased Risk of CNS Metastasis in Early-Stage NSCLC. Cancers 2021, 13, 3151. https://doi.org/10.3390/cancers13133151
Tsakonas G, Martín-Bernabé A, Rounis K, Moreno-Ruiz P, Botling J, De Petris L, Ylipää A, Mezheyeuski A, Micke P, Östman A, et al. High Density of NRF2 Expression in Malignant Cells Is Associated with Increased Risk of CNS Metastasis in Early-Stage NSCLC. Cancers. 2021; 13(13):3151. https://doi.org/10.3390/cancers13133151
Chicago/Turabian StyleTsakonas, Georgios, Alfonso Martín-Bernabé, Konstantinos Rounis, Pablo Moreno-Ruiz, Johan Botling, Luigi De Petris, Antti Ylipää, Artur Mezheyeuski, Patrick Micke, Arne Östman, and et al. 2021. "High Density of NRF2 Expression in Malignant Cells Is Associated with Increased Risk of CNS Metastasis in Early-Stage NSCLC" Cancers 13, no. 13: 3151. https://doi.org/10.3390/cancers13133151