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中国生物工程杂志

China Biotechnology
China Biotechnology  2023, Vol. 43 Issue (12): 60-68    DOI: 10.13523/j.cb.2310064
    
Correlation of CD27 Expression with Immune Status and Prognosis in Treatment-naive Patients with Multiple Myeloma
REN Xiao-tong,GUO Xin-yu,DUAN Yuan-jia,LIU Zhao-yun,SONG Nan,SHAO Zong-hong,FU Rong,LI Li-juan()
Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, China
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Abstract  

Objective: To investigate the expression of CD27 antigen in myeloma cells of multiple myeloma (MM) patients and its clinical diagnostic value. An analysis of the correlation between CD27 expression and cytogenetic abnormality, as well as the immune cell population will be provided. Methods: Immunophenotypes of myeloma cells in 124 MM patients were detected to analyze the expression of CD27 on malignant plasma cells, and the expression of T subsets, B subsets and Th1/Th2/Th17 subsets in peripheral blood. The presence of cytogenetic abnormalities, such as t (14; 16), p53 deletion, del (13q14.3), IGH rearrangement, t (4; 14), t (11; 14) and del (13q14) were analyzed. Clinical data of 124 patients were collected to compare whether there were significant differences between CD27+MM patients and CD27-MM patients. A total of 57 patients who underwent 4 courses of chemotherapy in our hospital were screened for efficacy evaluation, and to find the difference in efficacy evaluation between CD27+MM patients and CD27-MM patients. All patients who received treatment in our hospital were followed up for survival analysis. Results: The CD27+ rate of abnormal plasma cells was 29.03% (36/124) in 124 MM patients. By analyzing the clinical baseline data of CD27+MM and CD27-MM patients, statistically significant differences were found in lymphocyte count, serum creatinine, lactate dehydrogenase, and β2-microglobulin levels between two groups. Meanwhile, the cytogenetic and FISH results showed that the incidence of IGH rearrangement was lower in CD27+MM patients (31.58%) than in CD27-MM patients (53.41%). The R-ISS stratification in CD27+MM patients was lower than that in CD27-MM patients. The levels of CD19+B cells in CD27+MM patients were lower than those in CD27-MM patients, while the levels of TNF-α in Th1/Th2/Th17 subsets and the CD3+CD4+ T cell subsets in CD27+MM patients were higher than those in CD27-MM patients. After 4 courses of chemotherapy, the CR+VGPR rate was higher in CD27+MM patients than in CD27-MM patients. Conclusions: The low expression of CD27 on malignant plasma cells in MM patients may be related to the disease progression and poor prognosis.



Key wordsCD27 antigen      Multiple myeloma      Lymphocyte subgroups     
Received: 16 October 2023      Published: 16 January 2024
ZTFLH:  Q354  
Cite this article:

Xiao-tong REN, Xin-yu GUO, Yuan-jia DUAN, Zhao-yun LIU, Nan SONG, Zong-hong SHAO, Rong FU, Li-juan LI. Correlation of CD27 Expression with Immune Status and Prognosis in Treatment-naive Patients with Multiple Myeloma. China Biotechnology, 2023, 43(12): 60-68.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2310064     OR     https://manu60.magtech.com.cn/biotech/Y2023/V43/I12/60

基线资料 CD27阳性组(n=36) CD27阴性组(n=88) P
年龄/岁 62.5(46~82) 63(37~84) 0.084
性别(男/女) 15/21 49/39 0.156
CD56(+/-) 18/18 65/23 0.006
形态学恶性浆细胞比例/% 38.60±22.70 35.66±24.84 0.740
流式细胞术恶性浆细胞比例/% 8.69±6.88 8.99±10.48 0.440
血红蛋白浓度/(g/L) 93.27±27.93 91.06±23.61 0.681
淋巴细胞数(×109/L) 1.79±0.94 1.58±0.55 0.040
血清钙浓度/(mmol/L) 2.36±0.39 2.41±0.38 0.543
血肌酐浓度/(μmol/L) 123.38±84.96 184.88±252.63 0.048
白蛋白浓度/(g/L) 28.73±7.53 30.97±7.17 0.156
LDH浓度/(mmol/L) 168.2±39.10 206.11±82.76 0.005
β2-微球蛋白浓度/(g/L) 7.80±4.07 9.44±9.57 0.015
M蛋白比值/% 6.70±3.69 7.46±5.65 0.078
M蛋白浓度/(g/L) 19.55±12.68 21.60±15.66 0.590
β2-血清蛋白比值/% 6.91±8.06 9.09±12.41 0.041
β2-血清蛋白浓度/(g/L) 8.83±15.89 10.59±17.9 0.593
RISS分期(I/II/III) 4/23/9 8/41/39 0.039
ISS分期(I/II/III) 4/14/18 13/18/57 0.403
DS分期(IA/IB/IIA/IIB/IIIA/IIIB) 4/1/4/1/13/13 9/4/13/6/30/26 0.403
标危/高危 13/23 33/55 0.228
Table 1 Demographic and baseline characteristics of 124 patients with MM
淋巴细胞亚群 CD27阳性组/% CD27阴性组/% P
B细胞亚群
CD19+ 5.87±4.11 10.58±7.68 0.012
CD5+CD19+/CD19+ 20.17±23.05 13.82±11.76 0.280
Th1/Th2/Th17细胞亚群
IL-2 3.54±1.52 2.60±1.76 0.093
IL-4 5.15±3.68 6.53±13.09 0.668
IL-6 9.32±6.14 8.96±10.55 0.903
IL-10 10.12±10.26 5.61±3.43 0.078
TNF-α 3.90±1.89 2.65±1.61 0.037
IFN-γ 5.88±4.70 3.66±2.76 0.087
T细胞亚群
CD3+ 66.97±15.95 67.46±15.19 0.913
CD3+CD8+ 27.85±10.72 25.93±11.18 0.543
CD3+CD4+ 36.00±11.56 43.20±10.53 0.029
CD3+CD4+CD8+ 0.55±0.92 0.29±0.32 0.214
CD16+CD56+ 26.10±15.23 20.88±11.41 0.190
CD4/CD8值 1.54±0.97 1.99±0.97 0.173
Table 2 The expression of B subsets, Th1/Th2/Th17 subsets and T subsets in Peripheral blood of MM patients
细胞遗传学检测结果 CD27阳性组/人 CD27阴性组/人 P
细胞遗传学异常数目(0/1/2/3/4/5/6) 5/9/5/4/4/4/1 20/11/25/14/4/12/2 0.257
≥2个细胞遗传学异常 18(55.3%) 31(35.23%) 0.223
t(14;16)
p53
del(13q14.3)
IGH重排
1q21扩增
t(4;14)
t(11;14)
del(13q14)
高危细胞遗传学异常
高危细胞遗传学异常数目(0/1/2/3)
1(2.78%)
4(10.52%)
15(39.47%)
12(31.58%)
22(57.89%)
5(13.16%)
6(15.79%)
12(31.58%)
21/15
15/14/6/1
5(5.68%)
10(11.36%)
42(47.72%)
47(53.41%)
39(44.32%)
18(20.45%)
10(11.36%)
32(36.36%)
50/38
38/33/13/4
0.321
0.999
0.424
0.042
0.179
0.453
0.563
0.686
0.825
0.792
Table 3 Cytogenetic test results of 124 MM patients
疗效评价 CD27阳性组 CD27阴性组 P
CR 8(50%) 16(39.0%)
VGPR 6(37.5%) 7(17.1%)
PR 2(12.5%) 14(34.15%)
SD 0(0%) 0(0%)
PD 0(0%) 4(9.76%)
CR+VGPR 14 (87.5%) 23(56.1%) 0.032
PR+SD+PD 2 (12.5%) 18(43.9%)
蛋白酶体抑制剂使用率 92% 83% 0.990
Table 4 Efficacy evaluation of 57 patients with MM after 4 courses
Fig.1 Median overall survival (OS) times and median progression-free survival (PFS) times of patients with MM
[1]   Cannizzo E, Carulli G, Del Vecchio L, et al. The role of CD19 and CD 27 in the diagnosis of multiple myeloma by flow cytometry: a new statistical model. American Journal of Clinical Pathology, 2012, 137(3): 377-386.
doi: 10.1309/AJCP63TOCFNAMDMS pmid: 22338049
[2]   Rawstron A C, Orfao A, Beksac M, et al. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica, 2008, 93(3): 431-438.
[3]   Bataille R, Robillard N, Avet-Loiseau H, et al. CD221 (IGF-1R) is aberrantly expressed in multiple myeloma, in relation to disease severity. Haematologica, 2005, 90(5): 706-707.
pmid: 15921396
[4]   Moreaux J, Hose D, Reme T, et al. CD200 is a new prognostic factor in multiple myeloma. Blood, 2006, 108(13): 4194-4197.
doi: 10.1182/blood-2006-06-029355 pmid: 16946299
[5]   Ocqueteau M, Orfao A, Almeida J, et al. Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients: Implications for the differential diagnosis between MGUS and multiple myeloma. The American Journal of Pathology, 1998, 152(6): 1655-1665.
[6]   Rawstron A C, Owen R G, Davies F E, et al. Circulating plasma cells in multiple myeloma: characterization and correlation with disease stage. British Journal of Haematology, 1997, 97(1): 46-55.
pmid: 9136941
[7]   Terstappen L W, Johnsen S, Segers-Nolten I M, et al. Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry. Blood, 1990, 76(9): 1739-1747.
pmid: 2224123
[8]   Robillard N, Pellat-Deceunynck C, Bataille R. Phenotypic characterization of the human myeloma cell growth fraction. Blood, 2005, 105(12): 4845-4848.
doi: 10.1182/blood-2004-12-4700 pmid: 15741217
[9]   Pérez-Persona E, Vidriales M B, Mateo G, et al. New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood, 2007, 110(7): 2586-2592.
doi: 10.1182/blood-2007-05-088443 pmid: 17576818
[10]   Chu B, Bao L, Wang Y T, et al. CD27 antigen negative expression indicates poor prognosis in newly diagnosed multiple myeloma. Clinical Immunology, 2020, 213: 108363.
doi: 10.1016/j.clim.2020.108363
[11]   Taraban V Y, Rowley T F, Kerr J P, et al. CD27 costimulation contributes substantially to the expansion of functional memory CD8+T cells after peptide immunization. European Journal of Immunology, 2013, 43(12): 3314-3323.
doi: 10.1002/eji.201343579 pmid: 24002868
[12]   Agathanggelou A, Niedobitek G, Chen R, et al. Expression of immune regulatory molecules in Epstein-Barr virus-associated nasopharyngeal carcinomas with prominent lymphoid stroma: Evidence for a functional interaction between epithelial tumor cells and infiltrating lymphoid cells. The American Journal of Pathology, 1995, 147(4): 1152-1160.
[13]   Wajant H. Therapeutic targeting of CD70 and CD27. Expert Opinion on Therapeutic Targets, 2016, 20(8): 959-973.
doi: 10.1517/14728222.2016.1158812 pmid: 26914723
[14]   Hamann D, Kostense S, Wolthers K C, et al. Evidence that human CD8+CD45RA+CD27-cells are induced by antigen and evolve through extensive rounds of division. International Immunology, 1999, 11(7): 1027-1033.
pmid: 10383934
[15]   Katayama Y, Sakai A, Oue N, et al. A possible role for the loss of CD27-CD 70 interaction in myelomagenesis. British Journal of Haematology, 2003, 120(2): 223-234.
pmid: 12542479
[16]   Guikema J E J, Hovenga S, Vellenga E, et al. CD27 is heterogeneously expressed in multiple myeloma: low CD27 expression in patients with high-risk disease. British Journal of Haematology, 2003, 121(1): 36-43.
pmid: 12670329
[17]   Moreau P, Robillard N, Jégo G, et al. Lack of CD27 in myeloma delineates different presentation and outcome. British Journal of Haematology, 2006, 132(2): 168-170.
pmid: 16398651
[18]   Kumar S K, Callander N S, Alsina M, et al. NCCN guidelines insights: multiple myeloma, version 3.2018. Journal of the National Comprehensive Cancer Network, 2018, 16(1): 11-20.
doi: 10.6004/jnccn.2018.0002 pmid: 29295877
[19]   Palumbo A, Rajkumar S V, San Miguel J F, et al. International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 2014, 32(6): 587-600.
[20]   Starzer A M, Berghoff A S. New emerging targets in cancer immunotherapy: CD27 (TNFRSF7). ESMO Open, 2020, 4(Suppl 3): e000629.
doi: 10.1136/esmoopen-2019-000629
[21]   Takeda K, Oshima H, Hayakawa Y, et al. CD27-mediated activation of murine NK cells. The Journal of Immunology, 2000, 164(4): 1741-1745.
doi: 10.4049/jimmunol.164.4.1741
[22]   Morimoto S, Kanno Y, Tanaka Y, et al. CD134L engagement enhances human B cell Ig production: CD154/CD40, CD70/CD27, and CD134/CD134L interactions coordinately regulate T cell-dependent B cell responses. The Journal of Immunology, 2000, 164(8): 4097-4104.
doi: 10.4049/jimmunol.164.8.4097
[23]   Kobata T, Jacquot S, Kozlowski S, et al. CD27-CD70 interactions regulate B-cell activation by T cells. Proceedings of the National Academy of Sciences of the United States of America, 1995, 92(24): 11249-11253.
[24]   Alaterre E, Raimbault S, Goldschmidt H, et al. CD24, CD27, CD36 and CD302 gene expression for outcome prediction in patients with multiple myeloma. Oncotarget, 2017, 8(58): 98931-98944.
doi: 10.18632/oncotarget.22131 pmid: 29228738
[25]   Morgan T K, Zhao S C, Chang K L, et al. Low CD27 expression in plasma cell dyscrasias correlates with high-risk disease: an immunohistochemical analysis. American Journal of Clinical Pathology, 2006, 126(4): 545-551.
pmid: 16938662
[26]   王慧, 刘露, 刘芳, 等. CD27抗原在多发性骨髓瘤诊断中的价值. 中国实验血液学杂志, 2017, 25(4):1069-1073.
doi: 10.7534/j.issn.1009-2137.2017.04.019 pmid: 28823270
[26]   Wang H, Liu L, Liu F, et al. Diagnostic value of CD 27 antigen in patients with multiple myeloma. Journal of Experimental Hematology, 2017, 25(4): 1069-1073.
doi: 10.7534/j.issn.1009-2137.2017.04.019 pmid: 28823270
[27]   王晓雪, 张露露, 王童, 等. CD56表达情况在初诊多发性骨髓瘤患者预后中的价值及相关因素分析. 中国实验血液学杂志, 2023, 31(3):777-782.
[27]   Wang X X, Zhang L L, Wang T, et al. Prognostic value of CD 56 expression in newly diagnosed multiple myeloma patients and its related factors. Journal of Experimental Hematology. 2023, 31(3):777-782.
[28]   康晓芳, 张秀莲, 张伟华. IgH重排与多发性骨髓瘤预后的研究进展. 中华临床医师杂志(电子版), 2016, 10(20):3090-3094.
[28]   Kang X F, Zhang X L, Zhang W H. The progress of IgH rearrangement in the prognosis of multiple myeloma. Chinese Journal of Clinicians (Electronic Edition), 2016, 10(20):3090-3094.
[29]   王洪波. 多发性骨髓瘤患者血清β2-微球蛋白、肿瘤坏死因子-α、C反应蛋白及白介素-6水平检测的临床价值分析. 中国社区医师, 2020, 36(23):137-138.
[29]   Wang H B. Clinical value analysis of serum β2-microglobulin,TNF-α,CRP and IL-6 levels in patients with multiple myeloma. Chinese Community Doctors, 2020, 36(23):137-138.
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