The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines and Cell Culture
2.2. RNA Extraction, Reverse Transcription (RT), and Quantitative PCR (qPCR)
2.3. Protein Isolation and Western Blotting (WB)
2.4. Measurement of Total ACSLs Activity Using the Substrate [3H]-Palmitic Acid (PA)
2.5. Multiplex Immunofluorescence (mIF)
2.6. Immunohistochemistry (IHC)
2.7. Drug Treatment and Transfection
2.8. Cell Viability Assay
2.9. Data Analysis
3. Results
3.1. Expression and Enzymatic Activity of ACSL Isoforms in Normal Human Bronchial Epithelium (NHBE) Cells and Lung Cancer Cell Lines
3.2. Tissue Distribution of ACSL Isoforms in Normal Human Lung Tissues
3.3. The Correlation between the Expression of ACSL Isoforms and the Clinicopathological Parameters in Primary Lung Tumor Tissues
3.4. ACSL Enzymatic Activity after ACSL Inhibitor (Triacsin C) Treatment
3.5. The Effect of Triacsin C Combined with Chemotherapy/Targeted Therapeutic Drugs
3.6. The Effects of ACSL1, ACSL4, and ACSL5 Knockdown on Cell Viability
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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Sample Number | ACSL1 | p-Value | Sample Number | ACSL3 | p-Value | Sample Number | ACSL4 | p-Value | Sample Number | ACSL5 | p-Value | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
0 | 1–3 | 0–1 | 2–3 | 0–1 | 2–3 | 0 | 1–3 | ||||||||||
Type | ADC | 85 | 4 | 43 | 0.011 | 44 | 13 | 12 | 0.213 | 69 | 30 | 11 | 0.021 | 88 | 27 | 22 | 0 |
SCC | 12 | 26 | 14 | 5 | 27 | 1 | 38 | 1 | |||||||||
Gender | Male | 97 | 18 | 57 | 0.387 | 53 | 29 | 12 | 0.09 | 78 | 48 | 12 | 0.501 | 101 | 62 | 16 | 0.069 |
Female | 3 | 19 | 5 | 7 | 16 | 2 | 14 | 9 | |||||||||
Age | <60 | 97 | 4 | 29 | 0.124 | 53 | 7 | 9 | 0.042 | 78 | 18 | 8 | 0.037 | 101 | 24 | 9 | 0.683 |
≥60 | 17 | 47 | 27 | 10 | 46 | 6 | 52 | 16 | |||||||||
pT | 1–2 | 93 | 18 | 64 | 1 | 49 | 24 | 16 | 0.454 | 75 | 56 | 10 | 0.345 | 97 | 61 | 23 | 0.504 |
3–4 | 2 | 9 | 7 | 2 | 6 | 3 | 11 | 2 | |||||||||
pN | 0–1 | 91 | 12 | 51 | 0.519 | 49 | 20 | 15 | 0.202 | 73 | 45 | 7 | 0.127 | 95 | 45 | 19 | 0.210 |
2–4 | 7 | 21 | 11 | 3 | 15 | 6 | 26 | 5 | |||||||||
pM | 0 | 97 | 18 | 69 | 0.685 | 53 | 30 | 17 | 1 | 78 | 58 | 12 | 0.629 | 101 | 70 | 22 | 0.686 |
1–3 | 3 | 7 | 4 | 2 | 6 | 2 | 6 | 3 | |||||||||
Grade | 1–2 | 97 | 6 | 43 | 0.023 | 53 | 14 | 13 | 0.057 | 78 | 39 | 3 | 0.009 | 101 | 32 | 17 | 0.025 |
3–4 | 15 | 33 | 20 | 6 | 25 | 11 | 44 | 8 |
Type | Sample Number | Grade | ACSL1 | p-Value | Sample Number | Grade | ACSL3 | p-Value | Sample Number | Grade | ACSL4 | p-Value | Sample Number | Grade | ACSL5 | p-Value | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
0 | 1–3 | 0–1 | 2–3 | 0–1 | 2–3 | 0 | 1–3 | |||||||||||||
ADC | 47 | 1–2 | 0 | 25 | 0.026 | 25 | 1–2 | 4 | 9 | 0.027 | 41 | 1–2 | 20 | 3 | 0.024 | 49 | 1–2 | 10 | 15 | 0.03 |
3–4 | 4 | 18 | 3–4 | 9 | 3 | 3–4 | 10 | 8 | 3–4 | 17 | 7 | |||||||||
SCC | 38 | 1–2 | 6 | 16 | 0.503 | 19 | 1–2 | 10 | 3 | 1 | 28 | 1–2 | 17 | 0 | 0.393 | 39 | 1–2 | 21 | 1 | 1 |
3–4 | 6 | 10 | 3–4 | 4 | 2 | 3–4 | 10 | 1 | 3–4 | 17 | 0 |
50 Samples | ACSL1 | ACSL3 | ACSL4 | ACSL5 | ACSL6 |
---|---|---|---|---|---|
ACSL1 | 1 | r = 0.260, p = 0.069 | r = 0.039, p = 0.788 | r = 0.292, p = 0.04 | r = −0.123, p = 0.394 |
ACSL3 | 1 | r = −0.078, p = 0.589 | r = 0.246, p = 0.085 | r = −0.280, p = 0.048 | |
ACSL4 | 1 | r = −0.005, p = 0.972 | r = −0.064, p = 0.659 | ||
ACSL5 | 1 | r = −0.314, p = 0.026 | |||
ACSL6 | 1 |
ACSL1 vs. Ki67 | ACSL3 vs. Ki67 | ACSL4 vs. Ki67 | ACSL5 vs. Ki67 | ACSL6 vs. Ki67 | |
---|---|---|---|---|---|
Sample number | 88 | 51 | 72 | 86 | 85 |
Correlation coefficient (r Value) | 0.079 | 0.076 | 0.07 | −0.15 | −0.077 |
Sig. (two-tailed) p | 0.458 | 0.585 | 0.551 | 0.164 | 0.477 |
Grade 1–2 | 44 | 26 | 38 | 42 | 44 |
−0.122 | −0.243 | −0.293 | −0.36 | 0.079 | |
0.42 | 0.234 | 0.071 | 0.02 | 0.598 | |
Grade 3–4 | 44 | 25 | 34 | 44 | 41 |
0.232 | 0.397 | 0.063 | 0.102 | −0.241 | |
0.124 | 0.047 | 0.714 | 0.498 | 0.123 |
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Ma, Y.; Nenkov, M.; Berndt, A.; Abubrig, M.; Schmidt, M.; Sandhaus, T.; Huber, O.; Clement, J.H.; Lang, S.M.; Chen, Y.; et al. The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer. Cancers 2024, 16, 1170. https://doi.org/10.3390/cancers16061170
Ma Y, Nenkov M, Berndt A, Abubrig M, Schmidt M, Sandhaus T, Huber O, Clement JH, Lang SM, Chen Y, et al. The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer. Cancers. 2024; 16(6):1170. https://doi.org/10.3390/cancers16061170
Chicago/Turabian StyleMa, Yunxia, Miljana Nenkov, Alexander Berndt, Mohamed Abubrig, Martin Schmidt, Tim Sandhaus, Otmar Huber, Joachim H. Clement, Susanne M. Lang, Yuan Chen, and et al. 2024. "The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer" Cancers 16, no. 6: 1170. https://doi.org/10.3390/cancers16061170
APA StyleMa, Y., Nenkov, M., Berndt, A., Abubrig, M., Schmidt, M., Sandhaus, T., Huber, O., Clement, J. H., Lang, S. M., Chen, Y., & Gaßler, N. (2024). The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer. Cancers, 16(6), 1170. https://doi.org/10.3390/cancers16061170