Validation of a Proteomic Signature of Lung Cancer Risk from Bronchial Specimens of Risk-Stratified Individuals
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Cohorts and Collection of Bronchial Specimens
2.2. Tryptic Digestion of Proteins
2.3. SRM Assay Development
2.4. LC-SRM Analysis
2.5. SRM Data Analysis
2.6. Statistical Analysis
3. Results
3.1. Candidate Protein Selection for Validation
3.2. Validation of the Dysregulated Proteins
3.3. Dysregulated Proteins Discriminate High-Risk Groups from Low-Risk Groups
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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Protein Symbol | Protein Name |
---|---|
ACLY | ATP citrate lyase |
ACSF3 | Acyl-CoA synthetase family member 3 |
AKR1B10 | Aldo-keto reductase family 1, member B10 (aldose reductase) |
ALDH1A1 | Aldehyde dehydrogenase 1 family, member A1 |
ALDH3A1 | Aldehyde dehydrogenase 3 family, memberA1 |
ALOX15 | Arachidonate 15-lipoxygenase |
ANXA2 | Annexin A2 |
ANXA3 | Annexin A3 |
ANXA6 | Annexin A6 |
ATM | Ataxia telangiectasia mutated |
ATR | Ataxia telangiectasia and Rad3 related |
BCAS1 | Breast carcinoma amplified sequence 1 |
BRCA2 | Breast cancer type 2 susceptibility protein |
CAPS | Calcyphosine |
CEACAM5 | Carcinoembryonic antigen-related cell adhesion molecule 5 |
CTNNB1 | Catenin (cadherin-associated protein), beta 1, 88kDa |
DLG5 | Discs, large homolog 5 (Drosophila) |
DLST | Dihydrolipoamide S-succinyltransferase |
EGFR | Epidermal growth factor receptor |
EML2 | Echinoderm microtubule associated protein like 2 |
EML4 | Echinoderm microtubule associated protein like 4 |
FASN | Fatty acid synthase |
FXR1 | Fragile X mental retardation, autosomal homolog 1 |
G6PD | Glucose-6-phosphate dehydrogenase |
GLB1 | Galactosidase, beta 1 |
GLUD1 | Glutamate dehydrogenase 1 |
HSP90AA1 | Heat shock protein 90 kDa alpha (cytosolic), class A member 1 |
HSP90AB1 | Heat shock protein 90 kDa alpha (cytosolic), class B member 1 |
IDH1 | Isocitrate dehydrogenase 1 |
IDH2 | Isocitrate dehydrogenase 2 |
KMT2D | Histone-lysine N-methyltransferase 2D |
KRAS | Kirsten rat sarcoma viral proto-oncogene |
LDHA | Lactate dehydrogenase A |
LDHB | Lactate dehydrogenase B |
LGALS7B | Lectin, galactoside-binding, soluble, 7B |
ME2 | Malic enzyme 2, NAD(+)-dependent, mitochondrial |
MLF1 | Myeloid leukemia factor 1 |
MTHFD1 | C-1-tetrahydrofolate synthase, cytoplasmic |
MVP | Major vault protein |
NFKB1 | Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 |
PFKL | Phosphofructokinase, liver |
PFKP | Phosphofructokinase, platelet |
PGD | Phosphogluconate dehydrogenase |
PGK1 | Phosphoglycerate kinase 1 |
PGM1 | Phosphoglucomutase 1 |
PKM2 | Pyruvate kinase M2, muscle |
PRMT1 | Protein arginine methyltransferase 1 |
PYGB | Glycogen phosphorylase B |
S100A2 | S100 calcium binding protein A2 |
SERPINB1 | Serpin peptidase inhibitor, clade B (ovalbumin), member 1 |
SFN | Stratifin |
SFTPB | Surfactant protein B |
UBA1 | Ubiquitin-like modifier activating enzyme 1 |
UGP2 | UDP-glucose pyrophosphorylase 2 |
YWHAH | 14-3-3 protein eta |
Characteristics | Low Risk (n = 10) | High Risk (n = 10) | Lung Cancer (n = 10) | |
---|---|---|---|---|
Age | ||||
Average + St.Dev. | 61.8 ± 5.7 | 69.5 ± 4 | 73.5 ± 7.8 | |
Median (range) | 60.5 (55–74) | 69.5 (63–76) | 76 (57–82) | |
Gender | ||||
Male | 5 (50%) | 9 (90%) | 6 (60%) | |
Female | 5 (50%) | 1 (10%) | 4 (40%) | |
BMI | ||||
Average + St.Dev. | 27.5 ± 6 | 27.8 ± 3.8 | 22.5 ± 1.9 | |
Median (range) | 28 (19.7–37) | 27.5 (21.3–32.7) | 22.5 (19.3–25.8) | |
Smoking history | ||||
Never smoker | 4 (40%) | 0 (0%) | 1 (10%) | |
Former smoker | 6 (60%) | 4 (40%) | 7 (70%) | |
Current smoker | 0 (0%) | 6 (60%) | 2 (20%) | |
Pack year (Average + St.Dev.) * | 30.9 ± 28.7 | 73.4 ± 30.1 | 51.2 ± 30.3 | |
Pack year (median) | 23.5 (3.8–65) | 59 (47–129) | 45 (15–100) | |
COPD | ||||
Yes | 0 (0%) | 3 (30%) | 4 (40%) | |
No | 10 (100%) | 7 (70%) | 6 (60%) | |
Histology | ||||
Adenocarcinoma | - | - | 2 (20%) | |
Squamous cell carcinoma | - | - | 7 (70%) | |
Small-cell lung cancer | - | - | 1 (10%) | |
Path stage | ||||
No surgery | 4 (40%) | |||
Tx Nx Mx | - | - | 2 (20%) | |
IA | - | - | 1 (10%) | |
IB | - | - | 1 (10%) | |
IIA | - | - | 1 (10%) | |
IV | - | - | 1 (10%) |
Characteristics | Low Risk (n = 32) | High Risk (n = 34) | Lung Cancer (n = 83) | |
---|---|---|---|---|
Age | ||||
Average + St.Dev. | 63.1 ± 10.1 | 65.7 ± 7.4 | 66.4 ± 6.3 | |
Median (range) | 61 (43–87) | 66 (48–87) | 66 (53–85) | |
Gender | ||||
Male | 14 (44%) | 22 (65%) | 56 (67%) | |
Female | 18 (56%) | 12 (35%) | 27 (33%) | |
BMI | ||||
Average + St.Dev. | 27.9 ± 5.3 | 26.8 ± 5.2 | 27.1 ± 6.2 | |
Median (range) | 27.6 (15.5–39.1) | 26.1 (19.1–39) | 26.6 (18.1–53) | |
Smoking history | ||||
Never smoker | 10 (31%) | 0 (0%) | 1 (1%) | |
Former smoker | 19 (59%) | 14 (41%) | 36 (43%) | |
Current smoker | 3 (9%) | 20 (59%) | 46 (54%) | |
Pack year (Average + St.Dev.) | 14.9 ± 13.9 | 67.8 ± 25.7 | 53.2 ± 32.2 | |
Pack year (median) | 18 (0–50) | 61.5 (33–135) | 50 (0–200) | |
COPD | ||||
Yes | 7 (22%) | 27 (79%) | 61 (73%) | |
No | 25 (25%) | 7 (21%) | 22 (27%) | |
Histology | ||||
Adenocarcinoma | - | - | 37 (45%) | |
Squamous cell carcinoma | - | - | 38 (46%) | |
Adenosquamous cell ca. | - | - | 1 (1%) | |
Non-small-cell lung cancer | - | - | 3 (3%) | |
Large cell carcinoma | - | - | 1 (1%) | |
Large cell neuroendocrine | - | - | 2 (2%) | |
Small-cell lung cancer | - | - | 1 (10%) | |
Path stage | ||||
Stage 0 | 1 (1%) | |||
IA | - | - | 15 (18%) | |
IB | - | - | 11 (13%) | |
IIA | - | - | 1 (1%) | |
IIB | - | - | 9 (11%) | |
IIIA | - | - | 15 (18%) | |
IIIB | - | - | 6 (7%) | |
IIIC | - | - | 2 (2%) | |
IVA | - | - | 11 (13%) | |
IVB | - | - | 2 (2%) | |
Limited | - | - | 1 (1%) | |
Unknown | - | - | 9 (11%) |
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Rahman, S.M.J.; Chen, S.-C.; Wang, Y.-T.; Gao, Y.; Schepmoes, A.A.; Fillmore, T.L.; Shi, T.; Chen, H.; Rodland, K.D.; Massion, P.P.; et al. Validation of a Proteomic Signature of Lung Cancer Risk from Bronchial Specimens of Risk-Stratified Individuals. Cancers 2023, 15, 4504. https://doi.org/10.3390/cancers15184504
Rahman SMJ, Chen S-C, Wang Y-T, Gao Y, Schepmoes AA, Fillmore TL, Shi T, Chen H, Rodland KD, Massion PP, et al. Validation of a Proteomic Signature of Lung Cancer Risk from Bronchial Specimens of Risk-Stratified Individuals. Cancers. 2023; 15(18):4504. https://doi.org/10.3390/cancers15184504
Chicago/Turabian StyleRahman, S.M. Jamshedur, Sheau-Chiann Chen, Yi-Ting Wang, Yuqian Gao, Athena A. Schepmoes, Thomas L. Fillmore, Tujin Shi, Heidi Chen, Karin D. Rodland, Pierre P. Massion, and et al. 2023. "Validation of a Proteomic Signature of Lung Cancer Risk from Bronchial Specimens of Risk-Stratified Individuals" Cancers 15, no. 18: 4504. https://doi.org/10.3390/cancers15184504
APA StyleRahman, S. M. J., Chen, S. -C., Wang, Y. -T., Gao, Y., Schepmoes, A. A., Fillmore, T. L., Shi, T., Chen, H., Rodland, K. D., Massion, P. P., Grogan, E. L., & Liu, T. (2023). Validation of a Proteomic Signature of Lung Cancer Risk from Bronchial Specimens of Risk-Stratified Individuals. Cancers, 15(18), 4504. https://doi.org/10.3390/cancers15184504