[1]袁瑞丽a,孟 昊,刘 妮a,等.多发性骨髓瘤骨髓组织中BRD9和HNRNPA2B1表达水平与患者生存预后的相关性研究[J].现代检验医学杂志,2025,40(02):30-35.[doi:10.3969/j.issn.1671-7414.2025.02.006]
 YUAN Ruilia,MENG Hao,LIU Nia,et al.Expression Levels of BRD9 mRNA and HNRNPA2B1 mRNA in Bone Marrow Tissue of Multiple Myeloma Patients and Their Correlation with Survival Prognosis[J].Journal of Modern Laboratory Medicine,2025,40(02):30-35.[doi:10.3969/j.issn.1671-7414.2025.02.006]
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多发性骨髓瘤骨髓组织中BRD9和HNRNPA2B1表达水平与患者生存预后的相关性研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年02期
页码:
30-35
栏目:
论著
出版日期:
2025-03-15

文章信息/Info

Title:
Expression Levels of BRD9 mRNA and HNRNPA2B1 mRNA in Bone Marrow Tissue of Multiple Myeloma Patients and Their Correlation with Survival Prognosis
文章编号:
1671-7414(2025)02-030-06
作者:
袁瑞丽1a孟 昊2刘 妮1a柳 娟1b
(1. 西安交通大学第一附属医院 a. 检验科;b. 血液内科,西安 710061;2. 西安交通大学第二附属医院检验科,西安 710004)
Author(s):
YUAN Ruili1aMENG Hao2LIU Ni1aLIU Juan1b
(1a. Department of Clinical Laboratory;1b. Department of Hematology,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China;2. Department of Clinical Laboratory,the Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China)
关键词:
多发性骨髓瘤溴结构域蛋白9核不均一核糖核蛋白A2B1
分类号:
R733.3;R730.43
DOI:
10.3969/j.issn.1671-7414.2025.02.006
文献标志码:
A
摘要:
目的 分析多发性骨髓瘤(MM) 中溴结构域蛋白9(BRD9)、核不均一核糖核蛋白A2B1(HNRNPA2B1) 的表达水平及与患者生存预后的相关性。方法 选取2017 年5 月~ 2020 年5 月于西安交通大学第一附属医院诊治的102 例MM患者为MM 组,以60 例经骨髓穿刺明确无骨髓功能异常的患者为对照组。应用实时荧光定量PCR(qRT-PCR)检测骨髓组织BRD9 mRNA,HNRNPA2B1 mRNA 表达。Pearson 相关分析BRD9 mRNA 与HNRNPA2B1 mRNA 的相关性;Kaplan-Meier 曲线和COX 回归分析BRD9 mRNA,HNRNPA2B1 mRNA 表达与MM 患者生存预后的关系。结果 MM组骨髓组织BRD9 mRNA(3.14±0.66),HNRNPA2B1 mRNA(2.93±0.57)的相对表达量高于对照组(0.84±0.22,0.92±0.36),差异具有统计学意义(t=26.124,24.567,均P < 0.001)。Pearson 相关分析MM 组骨髓组织中BRD9mRNA 与HNRNPA2B1 mRNA 表达呈正相关(r=0.761,P < 0.001)。国际预后评分系统(ISS)分期Ⅲ期MM 组骨髓组织中BRD9 mRNA(3.90±0.69),HNRNPA2B1 mRNA(4.13±0.64)的相对表达量高于ISS 分期Ⅰ,Ⅱ期(2.70±0.60,3.15±0.65;2.23±0.51,2.95±0.56),差异具有统计学意义(t=7.399,4.272;13.255,7.551,均P < 0.05)。BRD9mRNA 高表达和低表达组三年总生存率分别为60.00%(30/50),82.69%(43/52),HNRNPA2B1 mRNA 高表达和低表达组三年总生存率分别为57.14%(28/49),84.91%(45/53),组间比较差异具有统计学意义(Log-Rank χ2=7.572,9.686,P=0.006,0.002)。ISS 分期Ⅲ期、BRD9 mRNA 高表达、HNRNPA2B1 mRNA 高表达是影响MM 患者不良生存预后的危险因素(均P < 0.001)。结论 MM 骨髓组织中BRD9,HNRNPA2B1 表达升高,两者均是影响MM 患者不良预后的危险因素。
Abstract:
Objective To analyze the bromodomain-containing protein 9 (BRD9) and heterogeneous nuclear ribonucleoprotein A2/B1(HNRNPA2B1) in the bromine domain of multiple myeloma (MM) and explore their correlation with the survival prognosis of MM patients. Methods A total of 102 MM patients who received treatment in the First Affiliated Hospital of Xi’an Jiaotong University from May 2017 to May 2020 were selected as the MM group, while 60 patients who were confirmed to have no bone marrow dysfunction through bone marrow puncture were selected as the control group. Real time fluorescence quantitative PCR (qRT-PCR)was applied to detect the expression of BRD9 mRNA and HNRNPA2B1 mRNA in bone marrow tissue. Pearson correlation analysis was applied to analyze the relationship between BRD9 mRNA and HNRNPA2B1 mRNA. Kaplan-Meier curve and COX regression analysis were used to investigate the relationship between BRD9 mRNA and HNRNPA2B1 mRNA expression and the survival prognosis of MM patients. Results The relative expression levels of BRD9 mRNA (3.14 ± 0.66) and HNRNPA2B1 mRNA (2.93 ± 0.57) in the bone marrow tissue of the MM group were higher than those in the control group (0.84 ± 0.22, 0.92 ± 0.36), and the differences were statistically significant (t=26.124, 24.567, all P<0.001). Pearson correlation analysis showed a positive correlation between BRD9 mRNA and HNRNPA2B1 mRNA expression in the bone marrow tissue of MM group (r=0.761, P<0.001). The relative expression levels of BRD9 mRNA(3.90±0.69)and HNRNPA2B1 mRNA(4.13±0.64)in the bone marrow tissue of the MM group with ISS stage III were higher than those in international staging system (ISS) stages I,II (2.70 ±0.60, 3.15 ± 0.65;2.23 ± 0.51, 2.95 ± 0.56), and the differences were statistically significant (t=7.399 ,4.272; 13.255, 7.551, all P<0.05). The 3-year overall survival rates of the BRD9 mRNA high expression and low expression groups were 60.00% (30/50) and 82.69% (43/52), respectively,the overall 3-year survival rates of HNRNPA2B1 mRNA high and low expression groups were 57.14% (28/49) and 84.91% (45/53), respectively, with statistically significant differences between the groups (Log Rank χ2=7.572, 9.686, P=0.006, 0.002). ISS stage III, high expression of BRD9 mRNA,and high expression of HNRNPA2B1 mRNA were risk factors affecting the poor survival prognosis of MM patients (all P<0.001). Conclusion The expression of BRD9 and HNRNPA2B1 are elevated in MM patients, both of them are risk factors for poor prognosis in MM patients.

参考文献/References:

[1] HEMMINKI K, F?RSTI A, HOULSTON R, et al. Epidemiology, genetics and treatment of multiple myeloma and precursor diseases[J]. International Journal of Cancer, 2021, 149(12): 1980-1996.
[2] 任梅, 石培民, 谢静, 等. 血清CXCL9 和IL-34 水平检测对多发性骨髓瘤患者的疗效监测及其预后价值[J]. 现代检验医学杂志,2023,38(5):127-132. REN Mei, SHI Peimin, XIE Jing, et al. Serum CXCL9 and IL-34 levels in multiple myeloma patients for monitoring efficacy and prognostic value[J]. Journal of Modern Laboratory Medicine, 2023, 38(5): 127-132.
[3] DU Jiahui, LIU Yili, WU Xiaolin, et al. BRD9-mediated chromatin remodeling suppresses osteoclastogenesis through negative feedback mechanism[J].Nature Communications, 2023, 14(1): 1413.
[4] ALPSOY A, UTTURKAR S M, CARTER B C, et al. BRD9 is a critical regulator of androgen receptor signaling and prostate cancer progression[J].Cancer Research, 2021, 81(4): 820-833.
[5] WANG Yuan, JIANG Xueyan, YU Xiyong. BRD9 controls the oxytocin signaling pathway in gastric cancer via Cana2D4, CALML6, GNAO1, and KCNJ5[J]. Translational Cancer Research, 2020, 9(5): 3354-3366.
[6] KIM H J, MOHASSEL P, DONKERVOORT S, et al. Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy[J].Nature Communications, 2022, 13(1): 2306.
[7] LIU Hao, LI Danxiu, SUN Lina, et al. Interaction of lncRNA MIR100HG with hnRNPA2B1 facilitates m6A-dependent stabilization of TCF7L2 mRNA and colorectal cancer progression[J]. Molecular Cancer, 2022, 21(1): 74-81.
[8] 中国医师协会血液科医师分会, 中华医学会血液学分会, 中国医师协会多发性骨髓瘤专业委员会. 中国多发性骨髓瘤诊治指南(2015 年修订)[J]. 中华内科杂志,2015,54(12):1066-1070. Chinese Hematology Association,Chinese Society of Hematology,Chinese Myeloma Committee-Chinese Hematology Association.Guidelines for the diagnosis and management of multiple myeloma in China (revised in 2015)[J].Chinese Journal of Internal Medicine, 2015, 54(12): 1066-1070.
[9] 中华医学会血液学分会. 多发性骨髓瘤骨病诊治指南[J]. 中华血液学杂志,2011,32(10):721-723. Chinese Society of Hematology,Chinese Medical Association . Cuidelines for treatment of myelome bone disease [J]. Chinese Journal of Hematology, 2011,32(10):721-723.
[10] 张燕, 沈茜. 实时逆转录聚合酶链反应检测细胞因子表达相对定量方法的建立[J]. 中华检验医学杂志,2003,26(10):591-593. ZHANG Yan, SHEN Qian. Establishment of relative quantification in real time reverse transcription polymerase chain reaction to measure cytokine expression[J]. Chinese Journal of Laboratory Medicine, 2003, 26(10): 591-593.
[11] MAIR N K, HALE B G. Ultra-rare BRD9 lossof-function variants limit the antiviral action of interferon[J]. Scientific Reports, 2022, 12(1): 15360.
[12] SABNIS R W. Novel compounds for targeted degradation of BRD9 and their use for treating cancer[J]. ACS Medicinal Chemistry Letters, 2022, 13(1): 17-18.
[13] ZHANG Chuanjie, CHEN Lu, LOU Weijuan, et al. Aberrant activation of m6A demethylase FTO renders HIF2αlow/- clear cell renal cell carcinoma sensitive to BRD9 inhibitors[J]. Science Translational Medicine, 2021, 13(613): 6045-6058.
[14] KURATA K, SAMUR M K, LIOW P, et al. BRD9 degradation disrupts ribosome biogenesis in multiple myeloma[J]. Clinical Cancer Research, 2023, 29(9): 1807-1821.
[15] XIE Dan, ZHANG Shuyi, JIANG Xiaocong, et al. Circ_CSPP1 regulates the development of non-small cell lung cancer via the miR-486-3p/BRD9 axis[J].Biochemical Genetics, 2023, 61(1): 1-20.
[16] FENG Yuliang, CAI Liuyang, POOK M, et al. BRD9-SMAD2/3 orchestrates stemness and tumorigenesis in pancreatic ductal adenocarcinoma[J]. Gastroenterology, 2024, 166(1): 139-154.
[17] WEISBERG E, CHOWDHURY B, MENG Chengcheng, et al. BRD9 degraders as chemosensitizers in acute leukemia and multiple myeloma[J]. Blood Cancer Journal, 2022, 12(7): 110.
[18] RUFFENACH G, MEDZIKOVIC L, ARYAN L, et al. HNRNPA2B1: RNA-binding protein that orchestrates smooth muscle cell phenotype in pulmonary arterial hypertension[J]. Circulation, 2022, 146(16): 1243-1258.
[19] TANG Jingzhi, CHEN Zhimin, WANG Qi, et al. HnRNPA2B1 promotes colon cancer progression via the MAPK pathway [J]. Frontiers in Genetics, 2021, 12: 666451.
[20] LIU Xin, LIU Yunze, LIU Zhao, et al. CircMYH9 drives colorectal cancer growth by regulating serine metabolism and redox homeostasis in a p53-dependent manner[J]. Molecular Cancer, 2021, 20(1): 114.
[21] JIANG Fengjie, TANG Xiaozhu, TANG Chao, et al. HNRNPA2B1 promotes multiple myeloma progression by increasing AKT3 expression via m6A-dependent stabilization of ILF3 mRNA[J]. Journal of Hematology & Oncology, 2021, 14(1): 54.
[22] JIA Chuiming, GUO Yiwei, CHEN Yao, et al. HNRNPA2B1-mediated m6A modification of TLR4 mRNA promotes progression of multiple myeloma[J].Journal of Translational Medicine, 2022, 20(1): 537.
[23] LIU Rui, ZHONG Yuping, CHEN Rui, et al. M6A reader hnRNPA2B1 drives multiple myeloma osteolytic bone disease[J]. Theranostics, 2022, 12(18): 7760-7774.
[24] JIANG Juan, ZHU Jiamei, QIU Ping, et al. HNRNPA2B1-mediated m6A modification of FOXM1 promotes drug resistance and inhibits ferroptosis in endometrial cancer via regulation of LCN2[J].Functional & Integrative Genomics, 2023, 24(1): 3.
[25] YANG Qiwei, VAFAEI S, FALAHATI A, et al. Bromodomain-containing protein 9 regulates signaling pathways and reprograms the epigenome in immortalized human uterine fibroid cells[J]. International Journal of Molecular Sciences, 2024, 25(2): 905.

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备注/Memo

备注/Memo:
基金项目:陕西省科学技术厅科技计划项目(2021SF-207)。
作者简介:袁瑞丽(1985-),女,硕士研究生,主管检验师,研究方向:临床检验诊断学,E-mail:yrl0211001@163.com。
更新日期/Last Update: 2025-03-15