Plasma Lysophosphatidylcholine Levels Correlate with Prognosis and Immunotherapy Response in Squamous Cell Carcinoma
Abstract
1. Introduction
2. Results
2.1. Correlation Between Clinical Data and Prognosis in Patients with SCC
2.2. Identification of Prognostic Factors Based on Targeted Metabolome Data via Weighted Gene Correlation Network Analysis (WGCNA)
2.3. LPC in Module 6 Shows a Correlation with Prognosis
2.4. Kaplan–Meier Survival Analysis Based on LPC Levels
2.5. Association of Decreased LPC with Biological Processes and Inflammatory Pathways
3. Discussion
4. Materials and Methods
4.1. Clinical Samples and Data
4.2. Metabolomics Analysis
4.3. Weighted Gene Correlation Network Analysis (WGCNA)
4.4. Proteomics Analysis
4.5. Cytokine Assay
4.6. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
SCC | Squamous cell carcinoma |
LPC | Lysophosphatidylcholine |
WGCNA | Weighted gene correlation network analysis |
OS | Overall survival |
GPS | Glasgow prognostic score |
CONUT | Controlling nutritional status |
HR | Hazard ratio |
CI | Confidence interval |
PS | Performance status |
PC | Phosphatidylcholine |
CE | Cholesteryl ester |
HC | Healthy cohort |
ICI | Immune checkpoint inhibitor |
PFS | Progression-free survival |
CRP | C-reactive protein |
LDL | Low-density lipoprotein |
HDL | High-density lipoprotein |
LPA | Lysophosphatidic acid |
irAE | Immune-related adverse events |
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Characteristic | Overall No. | 149 |
---|---|---|
Age | Median (range) | 69 (31–88) |
Sex | Male | 126 (85%) |
Female | 23 (15%) | |
BMI, kg/m2 | Median (range) | 21.3 (14.4–34.9) |
Body weight loss in past 6 months, n | ≥5% | 42 (28%) |
≥2% and BMI < 18.5 | 4 (3%) | |
Others | 103 (69%) | |
ECOG PS, n | 0 | 63 (42%) |
1 | 74 (50%) | |
2, 3 | 10 (7%) | |
Unknown | 2 (1%) | |
Primary lesion, n | Head and neck | 74 (50%) |
Nasopharynx | 7 (5%) | |
Oropharynx | 8 (5%) | |
Hypopharynx | 20 (13%) | |
Larynx | 5 (3%) | |
Oral cavity | 32 (21%) | |
Paranasal and nasal cavity | 1 (1%) | |
Ear canal | 1 (1%) | |
Esophagus | 75 (50%) | |
Treatment line at time of blood collection, n | Before 1st line administration | 21 (14%) |
1st line | 64 (43%) | |
2nd line | 46 (31%) | |
3rd line or later | 18 (12%) | |
Tumor diameter, mm | Median (range) | 36 (11–143) |
Number of organs with metastases | ≤1 | 123 (83%) |
≥2 | 26 (17%) | |
CONUT score | Median (range) | 4 (0–9) |
NLR | Median (range) | 3.9 (0.995–66.6) |
Glasgow prognostic score | 0 | 86 (58%) |
1 | 31 (21%) | |
2 | 32 (21%) | |
CRP, mg/dL | Median (range) | 0.46 (0.02–13.95) |
Albumin, g/dL | Median (range) | 3.8 (2.2–4.8) |
SCC, ng/mL | Median (range) | 1.80 (0.40–87.3) |
D-dimer, μg/mL | Median (range) | 1.3 (0.5–23.2) |
Hemoglobin, g/dL | Median (range) | 12.1 (7.8–17.0) |
Platelet, 103/μL | Median (range) | 251 (44–800) |
Leukocyte, /μL | Median (range) | 6400 (1900–15,500) |
HDL cholesterol, mg/dL | Median (range) | 17.8 (3.4–140.1) |
LDL/VLDL cholesterol, mg/dL | Median (range) | 91.8 (34.0–329.8) |
Total cholesterol, mg/dL | Median (range) | 113.0 (49.0–351.7) |
Mean Concentration (SD) | ||||
---|---|---|---|---|
Metabolites in Module 6 | Healthy Cohort | Patients | ||
GPS0 | GPS1 | GPS2 | ||
LPC 14:0 | 1.7 (0.6) | 1.4 (0.5) | 1.0 * (0.3) | 1.0 * (0.5) |
LPC 16:0 | 113.0 (29.4) | 91.3 (25.7) | 69.3 * (19.9) | 58.3 * (18.7) |
LPC 16:1 | 2.9 (1.0) | 2.9 (1.3) | 2.0 * (0.8) | 1.73 * (0.7) |
LPC 17:0 | 1.8 (0.5) | 1.3 (0.4) | 1.1 * (0.3) | 0.94 * (0.3) |
LPC 18:0 | 37.1 (0.2) | 25.0 (7.6) | 19.6 * (6.5) | 16.5 * (4.9) |
LPC 18:1 | 23.0 (7.1) | 18.9 (7.5) | 14.2 * (5.9) | 12.6 * (5.0) |
LPC 18:2 | 33.5 (13.5) | 29.4 (12.2) | 20.9 * (7.7) | 19.0 * (7.7) |
LPC 20:3 | 1.9 (0.7) | 1.5 (0.6) | 1.1 * (0.5) | 1.0 * (0.4) |
LPC 20:4 | 5.9 (2.0) | 4.8 (1.9) | 4.0 * (1.6) | 3.2 * (1.2) |
LPC 26:1 | 0.58 (0.7) | 0.32 (0.1) | 0.27 * (0.1) | 0.25 * (0.1) |
CE 16:1 | 21.1 (17.0) | 22.1 (16.0) | 15.1 * (9.0) | 12.6 * (6.8) |
CE 18:1 | 89.0 (64.9) | 108.3 (49.6) | 94.2 (56.8) | 76.1 * (33.7) |
CE 20:3 | 6.2 (3.9) | 5.3 (2.8) | 4.8 (2.9) | 4.4 (3.0) |
PC aa 28:1 | 3.4 (0.9) | 3.4 (1.1) | 3.0 * (0.9) | 2.9 * (0.9) |
PC aa 30:0 | 3.8 (1.2) | 3.8 (1.7) | 2.8 * (1.0) | 3.1 * (1.5) |
PC aa 32:1 | 13.4 (6.6) | 17.8 (15.9) | 10.9 * (5.5) | 11.4 * (7.3) |
PC aa 32:2 | 3.1 (1.1) | 2.8 (1.6) | 2.0 * (1.2) | 2.0 * (1.6) |
PC aa 34:1 | 199.6 (53.0) | 207.2 (82.1) | 166.0 * (48.4) | 166.8 * (52.7) |
PC aa 34:3 | 13.2 (3.9) | 14.1 (6.3) | 10.7 * (4.3) | 10.3 * (3.7) |
PC aa 34:4 | 1.4 (0.5) | 1.2 (0.6) | 0.87 * (0.4) | 0.79 * (0.4) |
PC aa 36:1 | 45.4 (11.2) | 39.4 (13.0) | 32.7 * (10.5) | 33.2 * (10.2) |
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Iwasaki, T.; Shirota, H.; Hishinuma, E.; Kawaoka, S.; Matsukawa, N.; Kasahara, Y.; Ouchi, K.; Imai, H.; Saijo, K.; Komine, K.; et al. Plasma Lysophosphatidylcholine Levels Correlate with Prognosis and Immunotherapy Response in Squamous Cell Carcinoma. Int. J. Mol. Sci. 2025, 26, 7528. https://doi.org/10.3390/ijms26157528
Iwasaki T, Shirota H, Hishinuma E, Kawaoka S, Matsukawa N, Kasahara Y, Ouchi K, Imai H, Saijo K, Komine K, et al. Plasma Lysophosphatidylcholine Levels Correlate with Prognosis and Immunotherapy Response in Squamous Cell Carcinoma. International Journal of Molecular Sciences. 2025; 26(15):7528. https://doi.org/10.3390/ijms26157528
Chicago/Turabian StyleIwasaki, Tomoyuki, Hidekazu Shirota, Eiji Hishinuma, Shinpei Kawaoka, Naomi Matsukawa, Yuki Kasahara, Kota Ouchi, Hiroo Imai, Ken Saijo, Keigo Komine, and et al. 2025. "Plasma Lysophosphatidylcholine Levels Correlate with Prognosis and Immunotherapy Response in Squamous Cell Carcinoma" International Journal of Molecular Sciences 26, no. 15: 7528. https://doi.org/10.3390/ijms26157528
APA StyleIwasaki, T., Shirota, H., Hishinuma, E., Kawaoka, S., Matsukawa, N., Kasahara, Y., Ouchi, K., Imai, H., Saijo, K., Komine, K., Takahashi, M., Ishioka, C., Koshiba, S., & Kawakami, H. (2025). Plasma Lysophosphatidylcholine Levels Correlate with Prognosis and Immunotherapy Response in Squamous Cell Carcinoma. International Journal of Molecular Sciences, 26(15), 7528. https://doi.org/10.3390/ijms26157528