Plasma Sphingosine-1-Phosphate Levels Are Associated with Progression of Estrogen Receptor-Positive Breast Cancer
Abstract
:1. Introduction
2. Results
2.1. Plasma S1P Levels Were Higher in Advanced BC Patients
2.2. Possibility of Suppression of S1P Signaling in ER-Positive BC
3. Discussion
4. Materials and Methods
4.1. Plasma Samples from BC Patients
4.2. Quantification of Sphingolipids by Mass Spectrometry
4.3. Comparison of Sphingolipid Levels in Plasma According to Clinicopathologic Characteristics of BC Patients
4.4. Cell Lines and Standard Culture Conditions
4.5. RNA Sequencing
4.6. Cell Viability Assay
4.7. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | Number of Patients (%) |
---|---|
Age (year) | |
<60 | 68 (54%) |
≥60 | 58 (46%) |
Menopausal status | |
Premenopause | 50 (40%) |
Postmenopause | 75 (59%) |
N.D. | 1 (1%) |
Body mass index | |
<25 | 85 (67%) |
≥25 | 41 (33%) |
Estrogen receptor expression | |
Negative | 0 (0%) |
Positive | 126 (100%) |
Progesterone receptor expression | |
Negative | 16 (13%) |
Positive | 110 (87%) |
HER2 overexpression/amplification | |
Negative | 107 (85%) |
Positive | 12 (10%) |
N.D. | 7 (6%) |
NSAS nuclear grade | |
1 | 73 (58%) |
2 | 24 (19%) |
3 | 27 (21%) |
N.D. | 2 (2%) |
Lymphatic invasion (ly) | |
Absent | 116 (92%) |
Present | 10 (8%) |
Venous invasion (v) | |
Absent | 121 (96%) |
Present | 5 (4%) |
Ki-67 labeling index | |
<20 | 77 (61%) |
≥20 | 49 (39%) |
Pathological primary tumor (pT) category * | |
pTis | 19 (15%) |
pT1 | 65 (52%) |
pT2 | 32 (25%) |
pT3 | 9 (7%) |
pT4 | 1 (1%) |
Pathological regional lymph node (pN) category * | |
pN0 | 90 (72%) |
pN1 | 23 (18%) |
pN2 | 8 (6%) |
pN3 | 4 (3%) |
pNX | 1 (1%) |
Pathological stage (pStage) * | |
pStage 0 | 19 (15%) |
pStage I | 50 (39%) |
pStage II | 41 (33%) |
pStage III | 15 (12%) |
N.D. | 1 (1%) |
DHS1P (pmol/mL) | Sph (pmol/mL) | DHSph (pmol/mL) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
No. | Median | (IQR) | p | Median | (IQR) | p | Median | (IQR) | p | |
Age (year) | 0.573 | 0.200 | 0.795 | |||||||
60 | 68 | 181.5 | (52.4) | 20.30 | (10.0) | 14.53 | (7.31) | |||
≥60 | 58 | 169.3 | (68.3) | 18.65 | (8.02) | 13.74 | (6.54) | |||
Menopause | 0.823 | 0.051 | 0.774 | |||||||
Premenopause | 50 | 179.7 | (57.3) | 21.65 | (10.59) | 14.48 | (6.88) | |||
Postmenopause | 75 | 172.4 | (60.5) | 18.65 | (8.22) | 14.00 | (6.70) | |||
Body mass index | 0.630 | 0.409 | 0.452 | |||||||
25 | 85 | 184.6 | (62.6) | 19.77 | (9.47) | 13.32 | (7.41) | |||
≥25 | 41 | 168.8 | (55.4) | 18.65 | (8.31) | 14.83 | (6.39) | |||
PgR expression | 0.069 | 0.369 | 0.026 | |||||||
Negative | 16 | 201.6 | (56.2) | 21.83 | (9.79) | 16.54 | (6.92) | |||
Positive | 110 | 175.5 | (59.1) | 19.02 | (8.74) | 13.42 | (6.97) | |||
HER2 expression | 0.934 | 0.196 | 0.873 | |||||||
Negative | 107 | 182.2 | (60.0) | 19.07 | (8.91) | 14.11 | (6.70) | |||
Positive | 12 | 168.5 | (69.3) | 18.11 | (6.93) | 12.43 | (8.31) | |||
NSAS nuclear grade | 0.029 | 0.104 | 0.085 | |||||||
1, 2 | 97 | 169.7 | (61.4) | 18.92 | (7.98) | 13.36 | (7.04) | |||
3 | 27 | 195.5 | (49.9) | 23.50 | (13.1) | 15.78 | (8.92) | |||
Lympatic invasion | 0.518 | 0.468 | 0.281 | |||||||
Negative | 116 | 179.3 | (62.8) | 19.49 | (8.89) | 13.74 | (7.08) | |||
Positive | 10 | 189.3 | (61.3) | 16.66 | (8.98) | 15.88 | (5.06) | |||
Vascular invasion | 0.151 | 0.942 | 0.372 | |||||||
Negative | 121 | 182.2 | (62.6) | 19.23 | (8.98) | 14.00 | (6.78) | |||
Positive | 5 | 161.6 | (28.4) | 18.65 | (9.44) | 15.83 | (8.68) | |||
Ki-67 labeling index | 0.568 | 0.667 | 0.897 | |||||||
20 | 77 | 181.9 | (58.4) | 19.23 | (8.45) | 14.46 | (6.32) | |||
≥20 | 49 | 176.7 | (64.9) | 18.86 | (12.44) | 14.11 | (7.46) | |||
pT | 0.066 | 0.332 | 0.261 | |||||||
is, 1 | 85 | 177.3 | (58.4) | 18.75 | (9.26) | 13.48 | (7.28) | |||
2–4 | 41 | 193.1 | (69.8) | 20.19 | (7.17) | 15.31 | (6.83) | |||
pN | 0.347 | 0.024 | 0.319 | |||||||
0 | 90 | 176.7 | (62.0) | 18.83 | (8.63) | 13.34 | (8.42) | |||
1–3 | 35 | 184.4 | (60.3) | 20.83 | (10.25) | 15.54 | (6.64) | |||
pStage | 0.036 | 0.037 | 0.241 | |||||||
0, I | 69 | 168.8 | (61.5) | 18.54 | (9.45) | 12.84 | (7.29) | |||
II, III | 56 | 186.1 | (60.3) | 20.45 | (7.57) | 15.28 | (7.25) |
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Ikarashi, M.; Tsuchida, J.; Nagahashi, M.; Takeuchi, S.; Moro, K.; Toshikawa, C.; Abe, S.; Ichikawa, H.; Shimada, Y.; Sakata, J.; et al. Plasma Sphingosine-1-Phosphate Levels Are Associated with Progression of Estrogen Receptor-Positive Breast Cancer. Int. J. Mol. Sci. 2021, 22, 13367. https://doi.org/10.3390/ijms222413367
Ikarashi M, Tsuchida J, Nagahashi M, Takeuchi S, Moro K, Toshikawa C, Abe S, Ichikawa H, Shimada Y, Sakata J, et al. Plasma Sphingosine-1-Phosphate Levels Are Associated with Progression of Estrogen Receptor-Positive Breast Cancer. International Journal of Molecular Sciences. 2021; 22(24):13367. https://doi.org/10.3390/ijms222413367
Chicago/Turabian StyleIkarashi, Mayuko, Junko Tsuchida, Masayuki Nagahashi, Shiho Takeuchi, Kazuki Moro, Chie Toshikawa, Shun Abe, Hiroshi Ichikawa, Yoshifumi Shimada, Jun Sakata, and et al. 2021. "Plasma Sphingosine-1-Phosphate Levels Are Associated with Progression of Estrogen Receptor-Positive Breast Cancer" International Journal of Molecular Sciences 22, no. 24: 13367. https://doi.org/10.3390/ijms222413367