Blood Res 2022; 57(4):
Published online December 31, 2022
https://doi.org/10.5045/br.2022.2022097
© The Korean Society of Hematology
Correspondence to : Istemi Serin, M.D.
Department of Hematology, Istanbul Training and Research Hospital, University of Health Sciences, Org. Nafiz Gurman Cad. Fatih 34098, Istanbul, Turkey
E-mail: serinistemi@hotmail.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
The suppressor of cytokine signaling-1 (SOCS-1) functions to induce an appropriate immune response and is an essential physiological regulator of interferon signaling. DNA methylation involves adding a methyl group to the carbon 5 position of cytosine. Besides comparing SOCS-1 gene methylation status between patients with multiple myeloma (MM) and healthy controls, this study also aimed to demonstrate the effect of SOCS-1 gene distribution and the effect of methylation of SOCS-1 on progression-free survival (PFS) and overall survival (OS).
Methods
This study included 120 patients diagnosed with MM between January 2018 and 2020 and 80 healthy individuals. The distribution of the SOCS-1 genotypes was statistically compared between MM patients and healthy controls. Additionally, the statistically significant effects of these genotypes on survival were examined.
Results
The CA/CA genotype of SOCS-1 was significantly higher in healthy controls (P=0.001), while the Del/Del genotype was significantly higher in patients with MM (P=0.034). The percent methylated reference (PMR) value of the SOCS-1 gene was significantly higher in the healthy controls (median, 43.48; range, 2.76‒247.75; P=0.001). Patients with a PMR value of ≥43.48 were 3.125 times more likely to develop progression than those with a PMR value of <43.48.
Conclusion
The effects of SOCS-1 polymorphisms on the pathogenesis of MM and SOCS-1 methylation will further shed light on the pathophysiology of MM.
Keywords: Multiple myeloma, SOCS-1, Epigenetics, Methylation, Survival
Blood Res 2022; 57(4): 250-255
Published online December 31, 2022 https://doi.org/10.5045/br.2022.2022097
Copyright © The Korean Society of Hematology.
Fatıma Ceren Tuncel1, Istemi Serin2, Sacide Pehlivan1, Yasemin Oyaci1, Mustafa Pehlivan3
1Department of Medical Biology, Faculty of Medicine, Institute of Health Sciences, Istanbul University, 2Department of Hematology, Istanbul Training and Research Hospital, University of Health Sciences, Istanbul, 3Department of Hematology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
Correspondence to:Istemi Serin, M.D.
Department of Hematology, Istanbul Training and Research Hospital, University of Health Sciences, Org. Nafiz Gurman Cad. Fatih 34098, Istanbul, Turkey
E-mail: serinistemi@hotmail.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
The suppressor of cytokine signaling-1 (SOCS-1) functions to induce an appropriate immune response and is an essential physiological regulator of interferon signaling. DNA methylation involves adding a methyl group to the carbon 5 position of cytosine. Besides comparing SOCS-1 gene methylation status between patients with multiple myeloma (MM) and healthy controls, this study also aimed to demonstrate the effect of SOCS-1 gene distribution and the effect of methylation of SOCS-1 on progression-free survival (PFS) and overall survival (OS).
Methods
This study included 120 patients diagnosed with MM between January 2018 and 2020 and 80 healthy individuals. The distribution of the SOCS-1 genotypes was statistically compared between MM patients and healthy controls. Additionally, the statistically significant effects of these genotypes on survival were examined.
Results
The CA/CA genotype of SOCS-1 was significantly higher in healthy controls (P=0.001), while the Del/Del genotype was significantly higher in patients with MM (P=0.034). The percent methylated reference (PMR) value of the SOCS-1 gene was significantly higher in the healthy controls (median, 43.48; range, 2.76‒247.75; P=0.001). Patients with a PMR value of ≥43.48 were 3.125 times more likely to develop progression than those with a PMR value of <43.48.
Conclusion
The effects of SOCS-1 polymorphisms on the pathogenesis of MM and SOCS-1 methylation will further shed light on the pathophysiology of MM.
Keywords: Multiple myeloma, SOCS-1, Epigenetics, Methylation, Survival
Table 1 . Clinical features and treatment regimens of patients with MM..
Multiple myeloma | ||
---|---|---|
Median | N=120 (%) | |
Age | 55 (32–70) | |
Gender | ||
Female/male | 56/64 (47/53) | |
Stage (Durie-Salmon) | ||
II/III | 29/69 (37.9/62.1) | |
ISS | ||
I | 31 (32) | |
II/III | 25/41 (25.8/41.3) | |
Hemoglobin | ||
gr/dL | 10.3 (6.2–15) | |
Leukocyte | ||
/mL | 6,900 (2,760–18,500) | |
Platelets | ||
/mL | 183,000 (103,000–406,000) | |
C-reactive protein | 7.2 (2.1–352) | |
mg/dL | ||
LDH | ||
IU/L | 203 (93–1,037) | |
B2-microglobulin | ||
mg/L | 5 (1.5-47.4) | |
Albumin | ||
gr/L | 3.5 (1.6–5.1) | |
Treatment | ||
VCD, ASCT, LD (%) | (100) | |
OS (5-year, %) | (80) | |
PFS (5-year, %) | (52) | |
Relapse | 44 (36.7) | |
Mortality | 18 (15) | |
Follow-up duration (mo) | 38.3 (4.1–105.3) |
Abbreviations: ASCT, autologous stem cell transplantation; IPI, International prognostic index; LD, lenalidomide, dexamethasone; LDH, lactate dehydrogenase; OS, overall survival; PFS, progression-free survival; VCD, bortezomib, cyclophosphamide, and dexamethasone..
Table 2 . Comparison of frequencies of SOCS-1 gene
SOCS-1 | Genotype | Multiple myeloma N=120 (%) | Healthy control N=80 (%) | OR Exp(B) | 95% CI | |
---|---|---|---|---|---|---|
SOCS-1 | CA/CA | 20 (16.7) | 30 (37.5) | 0.243a) | 0.106–0.558a) | 0.001a) |
CA/Del | 49 (40.8) | 29 (36.3) | 0.620a) | 0.294–1.309a) | 0.210a) | |
Del/Del | 51 (42.5) | 21 (26.2) | 0.498b) | 0.269–0.923b) | 0.034b) | |
Allele | ||||||
CA | 89 (37.1) | 89 (55.6) | ||||
Del | 151 (62.9) | 71 (44.4) | 2.127b) | 1.415–3.196b) | 0.001b) | |
2^-ΔΔCt | ×100 (PMR) | 20.11 (2.11–717.30) | 43.48 (2.76–247.75) | 0.001c) |
a)OR (95% CI) was adjusted by age and sex, b)Fisher’s Exact test, c)Median test..
Table 3 . Comparison of PFS and OS with prognostic factors of patients with MM..
N | PFS (5-year %) | Log-rank | OS (5-year %) | Log-rank | |
---|---|---|---|---|---|
Gender | 120 | 52 | 80 | ||
Female/male | 56/64 | 61/40 | 0.121 | 94/69 | 0.005 |
Age | |||||
<65/≥65 | 103/17 | 55/24 | 0.281 | 86/34 | 0.001 |
ISS | |||||
I | 31 | 61 | 92 | ||
II | 25 | 57 | 78 | ||
III | 41 | 40 | 0.632 | 62 | 0.008 |
ISS | |||||
I–II | 56 | 59 | 90 | ||
III | 41 | 40 | 0.363 | 63/62 | 0.002 |
ECOG | |||||
≤1/>1 | 113/7 | 52/42 | 0.951 | 81/50 | 0.668 |
LDH (IU/L) | |||||
<480/≥480 | 92/5 | 53/40 | 0.272 | 80/60 | 0.216 |
CRP (mg/L) | |||||
<5/≥5 | 44/53 | 59/44 | 0.217 | 91/67 | 0.015 |
SOCS-1 ( | |||||
CA/CA | 20 | 27 | 81 | ||
CA/Del | 49 | 63 | 80 | ||
Del/Del | 51 | 52 | 0.229 | 78 | 0.763 |
SOCS-1 ( | |||||
CA/CA | 20 | 27 | 81 | ||
CA/Del+Del/Del | 100 | 57 | 0.140 | 79 | 0.462 |
2^-ΔΔCt×100 (PMR) | |||||
<43.48 | 84 | 56 | 82 | ||
≥43.48 | 36 | 43 | 0.027 | 77 | 0.484 |
Abbreviations: CRP, C-reactive protein; ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System; LDH, lactate dehydrogenase; OS, overall survival; PFS, progression-free survival; PMR, percent methylated reference; SOCS-1, suppressor of cytokine signaling-1..
Table 4 . Statistical analysis according to the PMR cut-off value of 43.48..
2^-ΔΔCt×100 (PMR) <43.48 N=84 (%) | 2^-ΔΔCt×100 (PMR) ≥43.48 N=36 (%) | OR Exp(B) | 95% CI | ||
---|---|---|---|---|---|
Progression | |||||
(+) | 24 (28.6) | 20 (55.6) | |||
(-) | 60 (71.4) | 16 (44.4) | 3.125a) | 1.390–7.025a) | 0.006 |
a)OR (95% CI) was adjusted by age and sex..
Abbreviation: PMR, percent methylated reference..
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