Interleukin-11: A Potential Biomarker and Molecular Therapeutic Target in Non-Small Cell Lung Cancer
Abstract
:1. Brief Overview of NSCLC Management and Importance of Biomarkers in Clinical Context
2. Interleukin-11: Member of the IL6 Family of Cytokines
3. Interleukin 11 Drives Pulmonary Fibrosis and Inflammation
4. Interleukin 11 Is a Tumor-Promoting Cytokine in NSCLC
5. Sources of Biomarkers in NSCLC
6. IL11 Differential Expression in NSCLC Tumor Tissue
7. Detection of IL11 for Diagnosis of NSCLC
8. Quantification of IL11 Expression for Prognostication of NSCLC
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cytokine | Receptors | References |
---|---|---|
IL6 | IL6R, gp130/IL6ST | [15,16,17,18,19,20,21,22] |
IL-31 | IL31Rα, OSMR | [23] |
LIF | LIFR/LIFRα, gp130/IL6ST | [24] |
OSM | OSMR/OSMRβ, gp130/IL6ST, LIFR | [25,26] |
CLCF1 | CNTFR, LIFR, gp130/IL6ST | [22,27] |
Study | Recruited Population | Comparison | Sample Type | Diagnostic Biomarker | Assay | Receiver Operator Curve and Test Metrics | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
AUC (95% CI) | Cutoff (pg/mL) | Sensitivity (95% CI) | Specificity (95% CI) | PPV (95% CI) | NPV (95% CI) | ||||||
Pastor et al. [90] | Age > 40 yrs, current or ex-smokers of 30 pack-years, evaluated for hemoptysis or pulmonary nodule or mass, excluding those with prior diagnosis of malignancy, active tuberculosis, history of drug abuse or other inflammatory disease apart from COPD | LUAD vs. non-LUAD—First validation cohort (n = 149) | BALF | IL11 protein | ELISA | 0.93 (0.90–0.97) | 42.0 | 90.2 (79–95.7) | 88.7 (90.6–93.5) | 80.7 (68.7–88.9) | 94.5 (87.8–97.6) |
LUAD vs. non-LUAD—Second validation cohort (n = 160) | BALF | IL11 protein | ELISA | 0.95 (0.92–0.98) | 42.0 | 90.6 (79.7–95.9) | 83.0 (86.8–87.7) | 60.8 (49.7–70.8) | 96.8 (92.7–98.6) | ||
Wu et al. [91] | NSCLC patients with no history of radiochemotherapy, immune-targeted therapy or surgery (n = 91 for serum, of which 63 have LUAD and 28 have SCC; 64 for EBC) | Healthy volunteers without acute or chronic infectious diseases, vital organ diseases, or genetic family tumor history (n = 72 for serum; 63 for EBC) | Serum | IL11 protein | ELISA | 0.93 (0.88–0.97) | 126.1 | 75.0 | 100.0 | NR | NR |
EBC | IL11 protein | ELISA | 0.78 (0.69–0.86) | 21.5 | 78.1 | 79.4 | NR | NR |
Pathology | Comparison | Source | Findings | Reference |
---|---|---|---|---|
Polycythemia vera | Healthy | Plasma | Increased | [97] |
Rheumatoid arthritis with or without interstitial lung disease | Healthy | Serum | Increased in rheumatoid arthritis, more so with concomitant interstitial lung disease | [98] |
Congestive heart failure | Healthy | Plasma | Increased | [99] |
Severe pancreatitis | Mild pancreatitis | Serum | Increased | [100] |
Breast cancer metastatic to bone | Primary breast cancer and healthy controls | Serum | Increased compared to healthy controlsCorrelated with shorter disease-free survival | [101] |
Pancreatic cancer | Healthy | Plasma | Increased Correlated with survival. | [102] |
Gastric cancer | Chronic superficial gastritis and chronic atrophic Gastritis | Serum | Increased in gastric cancer > chronic atrophic gastritis > chronic superficial gastritis | [103] |
Preeclampsia | Normal pregnant gestation-matched control | Serum | Increased | [104] |
Thoracic aortic dissection | Non-aortic dissection patients presenting with chest pain | Plasma | Increased | [105] |
Study | Year | Training Cohort | Validation Cohort (s) | Cancer Type | Prognostic Signature | Findings |
---|---|---|---|---|---|---|
Kratz et al. [107] | 2012 | Non-squamous NSCLC (n = 361) | Stage I non-squamous NSCLC (n = 433), and stage I-III non-squamous NSCLC (n = 1006) | Non-squamous NSCLC | 11 Target genes (BAG1, BRCA1, CDC6, CDK2AP1, ERBB3, FUT3, IL11, LCK) and 3 reference genes (ESD, TBP, YAP1) |
|
Watza et al. [108] | 2018 | NSCLC patients without history of bronchiectasis or cystic fibrosis (n = 280) | TCGA Lung SCC and TCGA LUAD datasets (n = 1026) | NSCLC | 23 genes involved in the interleukin signaling pathway, including IL11 |
|
Wang et al. [79] | 2020 | TCGA LUAD dataset (497 LUAD tissues, 54 normal lung tissues) | n/a | LUAD | 6 genes (CRABP1, IGKV4-1, IL11, INHA, LGR4, VIPR1) |
|
Fan et al. [109] | 2021 | TGCA LUAD dataset (n = 464)(majority stage I and II) | GSE13213 (n = 117), GSE30219 (n = 85), GSE31210 (n = 226), GSE72094 (n = 420)(majority stage I and II) | LUAD | 5 genes (IL7R, IL5RA, IL20RB, IL11, IL22RA1) |
|
Chen et al. [110] | 2021 | TCGA LUAD (535 LUAD tissues, 59 normal lung tissues)GSE161116 (9 LUAD tissues, 9 LUAD brain metastasis tissues) | n/a | LUAD | 6 genes (TNFRSF11A, MS4A2, IL11, CAMP, MS4A1, F2RL1) |
|
Peng et al. [111] | 2021 | GSE161116 (13 lung tumor tissues, 15 brain tissues), GSE747706 (18 lung tumor tissues, 18 normal tissues), GSE21933 (21 lung tumor tissues, 21 normal tissues) datasets | n/a | NSCLC andBrain tumor | n/a |
|
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Leung, J.H.; Ng, B.; Lim, W.-W. Interleukin-11: A Potential Biomarker and Molecular Therapeutic Target in Non-Small Cell Lung Cancer. Cells 2022, 11, 2257. https://doi.org/10.3390/cells11142257
Leung JH, Ng B, Lim W-W. Interleukin-11: A Potential Biomarker and Molecular Therapeutic Target in Non-Small Cell Lung Cancer. Cells. 2022; 11(14):2257. https://doi.org/10.3390/cells11142257
Chicago/Turabian StyleLeung, Jason Hongting, Benjamin Ng, and Wei-Wen Lim. 2022. "Interleukin-11: A Potential Biomarker and Molecular Therapeutic Target in Non-Small Cell Lung Cancer" Cells 11, no. 14: 2257. https://doi.org/10.3390/cells11142257
APA StyleLeung, J. H., Ng, B., & Lim, W.-W. (2022). Interleukin-11: A Potential Biomarker and Molecular Therapeutic Target in Non-Small Cell Lung Cancer. Cells, 11(14), 2257. https://doi.org/10.3390/cells11142257