The research on the association between genetic alterations of DLBCLs and <sup>18</sup>F-FDG PET/CT SUV<sub>max</sub> and their clinical significance

Tian TIAN; Chen CHEN; Ran WEI; Longlong BAO; Bingxin GU; Qunling ZHANG; Junning CAO; Baohua YU; Xiaoqiu LI; Xiaoyan ZHOU

doi:10.19401/j.cnki.1007-3639.2025.06.002

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The research on the association between genetic alterations of DLBCLs and ¹⁸F-FDG PET/CT SUV_max and their clinical significance

Article | 更新时间：2025-12-31

- The research on the association between genetic alterations of DLBCLs and ¹⁸F-FDG PET/CT SUV_max and their clinical significance
- China Oncology Vol. 35, Issue 6, Pages: 531-542(2025)
- 作者机构：
  
  1. 复旦大学附属肿瘤医院病理科，复旦大学上海医学院肿瘤学系，复旦大学病理研究所，上海 200032
  2. 复旦大学附属肿瘤医院核医学科，复旦大学上海医学院肿瘤学系，上海 200032
  3. 复旦大学附属肿瘤医院肿瘤内科，复旦大学上海医学院肿瘤学系，上海 200032
- 作者简介：
  
  ZHOU Xiaoyan
- 基金信息：
  
  Shanghai Collaborative Innovation Cluster(2019CXJQ03);Special Program for Medical Innovation Research (Science and Technology Innovation Action Plan, Shanghai Municipal Science and Technology Commission)(20Z11900300)
- DOI：10.19401/j.cnki.1007-3639.2025.06.002
  CLC： R733.4
- Received：20 February 2025，
  
  Revised：2025-03-26，
  
  Published：30 June 2025
- 稿件说明：
移动端阅览
Tian TIAN, Chen CHEN, Ran WEI, et al. The research on the association between genetic alterations of DLBCLs and ¹⁸F-FDG PET/CT SUV_max and their clinical significance[J]. China Oncology, 2025, 35(6): 531-542.
DOI：

Tian TIAN, Chen CHEN, Ran WEI, et al. The research on the association between genetic alterations of DLBCLs and ¹⁸F-FDG PET/CT SUV_max and their clinical significance[J]. China Oncology, 2025, 35(6): 531-542. DOI： 10.19401/j.cnki.1007-3639.2025.06.002.

摘要

背景与目的：

弥漫性大B细胞淋巴瘤（diffuse large B cell lymphoma，DLBCL）分子遗传学特征和患者治疗前

F-FDG PET/CT检查评估的SUV

max

值均与患者预后密切相关，但两者的关系及其与R-CHOP治疗方案治疗反应的相关性尚不清楚。本研究旨在分析DLBCL分子遗传学特征与治疗前经

F-FDG PET/CT检测的SUV

max

值的关系及其与临床病理学特征、R-CHOP治疗反应的相关性。

方法：

回顾性收集复旦大学附属肿瘤医院2022—2023年同时经淋巴瘤481基因DNA panel二代测序（next-generation sequencing，NGS）和治疗前经PET/CT检查的DLBCL患者225例，本研究通过复旦大学附属肿瘤医院医学伦理委员会的审查（伦理批号：050432-4-2307E）并获得患者知情同意；除基因突变特征外，同时收集荧光原位杂交法检测的

BCL2

、

BCL6

和

MYC

基因易位情况；另收集该组病例的临床病理学参数以及经R-CHOP治疗后的PET/CT检查结果。

结果：

总计191例DLBCL患者纳入最终分析，重要基因

MYD88

突变、

TP53

突变、

CDKN2A

拷贝数异常、

CD79B

突变发生率分别为24.6%、27.2%、32.5%和16.8%。治疗前SUV

max

值范围是5.10~63.10（24.44±10.70，中位22.80）。

MYD88

L265P

突变型DLBCL的治疗前SUV

max

值显著高于

MYD88

野生型DLBCL（

=0.039），SUV

max

值与DLBCL其他基因变异类型包括

TP53

突变、

CDKN2A/B

拷贝数减少、

CD79B

突变、

KMT2D

突变、

TNFAIP3

突变、

B2M

突变、

EZH2

突变、

BTG1/2

突变、

CREBBP

突变、

MYC

、

BCL2

、

BCL6

基因重排之间无显著的相关性。治疗前高SUV

max

值与高血清乳酸脱氢酶（lactate dehydrogenase，LDH）水平（

=0.012）及非生发中心（non-germinal center B-cell-like，non-GCB）亚型显著相关（

=0.040），但与R-CHOP治疗反应无显著的相关性（

=0.714）。DLBCL中

TP53

基因突变与R-CHOP治疗反应差显著相关（

=0.001），是R-CHOP治疗后非完全代谢缓解的独立预测因子。联合

TP53

基因突变、Ann Arbor分期、国际预后指数（International Prognostic Index，IPI）及血清LDH水平能够更好地预测患者对R-CHOP治疗的反应。

结论：

在DLBCL中，

MYD88

L265P

突变型患者具有较高的治疗前SUV

max

值。DLBCL治疗前SUV

max

值与R-CHOP治疗反应无关，而

TP53

基因突变与R-CHOP治疗反应差显著相关，并且是独立预测因子。

TP53

基因突变联合临床病理学参数可更好地预测R-CHOP治疗反应。关于各基因变异特征及SUV

max

值与患者预后的关系尚需作进一步随访研究。

Abstract

Background and purpose:

Next generation sequencing-identified genetic alterations of diffuse large B cell lymphoma (DLBCL) and baseline SUV

max

detected by

F-FDG PET/CT were correlated with patients’ prognosis. However

their relationship and the associations with R-CHOP response of DLBCL are still unclear. This study aimed to analyze the association bewteen genetic alterations and

F-FDG PET/CT SUV

max

and their correlations with clinicopathological characteristics and R-CHOP response of DLBCL.

Methods:

A total of 225 cases of primary DLBCL detected by next generation sequencing using 481 lymphoma gene panel and examined by

F-FDG PET/CT before treatment between 2022 and 2023 were collected. This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (Ethical No.: 050432-4-2307E) and acquired the informed consent of the patients. The translocations of

BCL2

BCL6

and

MYC

were identified by fluorescence

in situ

hybridization. The clinicopathological characteristics and the PET/CT scan after R-CHOP chemotherapy were collected.

Results:

Finally

191 patients were enrolled in this study. The frequency of

MYD88

mutation

TP53

mutation

copy number variations of

CDKN2A/2B

CD79B

mutation in the 191 DLBCL patients were 24.6%

27.2%

32.5% and 16.8%

respectively. The range of baseline SUV

max

was 5.10-63.10 (24.44±10.70

median 22.80). The baseline SUV

max

MYD88

L265P

DLBCL was significantly higher than that of

MYD88

wild type (

=0.039). There were no significant associations of SUV

max

with other gene alterations including

TP53

mutation

CDKN2A/B

loss

CD79B

mutation

KMT2D

mutation

TNFAIP3

mutation

B2M

mutation

EZH2

mutation

BTG1/2

mutation

CREBBP

mutation

gene translocations of

MYC

BCL2

and

BCL6

. The higher SUV

max

before treatment was correlated with higher serum lactate dehydrogenase (LDH) level (

=0.012) and non-germinal center B-cell-like (non-GCB) DLBCL (

=0.040). However

there was no significant association of SUV

max

with R-CHOP response (

=0.714).

TP53

mutation was significantly associated with the poor response of R-CHOP (

=0.001) and was an independent predictor of non-complete metabolic response (non-CMR).

TP53

mutation combined with Ann Arbor stage

International Prognostic Index (IPI) score and serum LDH level could better predict R-CHOP response than each factor alone.

Conclusion:

MYD88

L265P

DLBCL had higher baseline

F-FDG PET/CT SUV

max

. The baseline SUV

max

was not associated with R-CHOP response. However

TP53

mutation was significantly correlated with poor response of R-CHOP in DLBCL patients.

TP53

mutation combined with clinicopathological characteristics could better predict R-CHOP response. The associations of gene alterations and SUV

max

with prognosis of DLBCL patients needed to be explored in the future.

关键词

Keywords

references

CUTMORE N H , KRUPKA J A , HODSON D J . Genetic profiling in diffuse large B-cell lymphoma: the promise and the challenge [J ] . Mod Pathol , 2023 , 36 ( 1 ): 100007 .

CHEN Y , CHEN Z J , TAN X Y , et al . Role of body composition and metabolic parameters extracted from baseline 18 F-FDG PET/CT in patients with diffuse large B-cell lymphoma [J ] . Ann Hematol , 2023 , 102 ( 10 ): 2779 - 2789 .

GUI J B , LI M T , XU J , et al . 18 F-FDG PET/CT for prognosis and toxicity prediction of diffuse large B-cell lymphoma patients with chimeric antigen receptor T-cell therapy [J ] . Eur J Nucl Med Mol Imaging , 2024 , 51 ( 8 ): 2308 - 2319 .

IKEDA D , OURA M , UEHARA A , et al . Prognostic relevance of tumor-infiltrating CD4 + cells and total metabolic tumor volume-based risk stratification in diffuse large B-cell lymphoma [J ] . Haematologica , 2024 , 109 ( 9 ): 2822 - 2832 .

WRIGHT G W , HUANG D W , PHELAN J D , et al . A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications [J ] . Cancer Cell , 2020 , 37 ( 4 ): 551 - 568 .e14. DOI: S1535-6108(20)30155-0 http://doi.org/S1535-6108(20)30155-0

LACY S E , BARRANS S L , BEER P A , et al . Targeted sequencing in DLBCL, molecular subtypes, and outcomes: a Haematological Malignancy Research Network report [J ] . Blood , 2020 , 135 ( 20 ): 1759 - 1771 . DOI: 10.1182/blood.2019003535 http://doi.org/10.1182/blood.2019003535

KIM G , KIM J , CHA H , et al . Metabolic radiogenomics in lung cancer: associations between FDG PET image features and oncogenic signaling pathway alterations [J ] . Sci Rep , 2020 , 10 ( 1 ): 13231 . DOI: 10.1038/s41598-020-70168-x http://doi.org/10.1038/s41598-020-70168-x

LEE D Y , OH J S , KIM J W , et al . Pre-operative dual-time-point [ 18 F ] FET/PET differentiates CDKN2A/B loss and PIK3CA mutation status in adult-type diffuse glioma: a single-center prospective study [J ] . Eur J Nucl Med Mol Imaging , 2025 , 52 ( 2 ): 669 - 682 .

SCHWARTZENBERG-BAR-YOSEPH F , ARMONI M , KARNIELI E . The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression [J ] . Cancer Res , 2004 , 64 ( 7 ): 2627 - 2633 .

HINDES M T , MCELLIGOTT A M , BEST O G , et al . Metabolic reprogramming, malignant transformation and metastasis: lessons from chronic lymphocytic leukaemia and prostate cancer [J ] . Cancer Lett , 2025 , 611 : 217441 .

LIAO Q , DENG J , TONG J , et al . p53 induces circFRMD4A to suppress cancer development through glycolytic reprogramming and cuproptosis [J ] . Mol Cell , 2025 , 85 ( 1 ): 132 - 149 .e7. DOI: 10.1016/j.molcel.2024.11.013 http://doi.org/10.1016/j.molcel.2024.11.013

MANDATO E , YAN Q S , OUYANG J , et al . MYD88 L265P augments proximal B-cell receptor signaling in large B-cell lymphomas via an interaction with DOCK8 [J ] . Blood , 2023 , 142 ( 14 ): 1219 - 1232 .

MOHAMED A H , ELFEKY M A , ELSHORBAGY S , et al . Prognostic values of myeloid differentiation factor 88 (MYD88) and transducin (β)-like receptor 1 (TBLR1) expression in tissues of diffuse large B-cell non-Hodgkin lymphoma patients - an immunohistochemical study [J ] . Contemp Oncol (Pozn) , 2022 , 26 ( 1 ): 49 - 58 .

EBID O A E H , EZZ EL ARAB L R , SAAD A S , et al . Prognostic impact of MYD88 and TP53 mutations in diffuse large B cell lymphoma [J ] . Ann Hematol , 2023 , 102 ( 12 ): 3477 - 3488 .

YOUNES A , SEHN L H , JOHNSON P , et al . Randomized phase Ⅲ trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma [J ] . J Clin Oncol , 2019 , 37 ( 15 ): 1285 - 1295 .

ZHANG M C , TIAN S , FU D , et al . Genetic subtype-guided immunochemotherapy in diffuse large B cell lymphoma: the randomized GUIDANCE-01 trial [J ] . Cancer Cell , 2023 , 41 ( 10 ): 1705 - 1716 .e5.

RYU J M , JEONG Y Y , LEE S J , et al . Association between preoperative 18-FDG PET-CT SUV max and next-generation sequencing results in postoperative ovarian malignant tissue in patients with advanced ovarian cancer [J ] . J Clin Med , 2023 , 12 ( 6 ): 2287 .

HAGHIGHAT JAHROMI A , CHANG G , KURZROCK R , et al . Standardized uptake value (SUV max ) in 18 F-FDG PET/CT is correlated with the total number of main oncogenic anomalies in cancer patients [J ] . Cancer Biol Ther , 2020 , 21 ( 11 ): 1067 - 1071 .

MICHAUD L , BANTILAN K , MAUGUEN A , et al . Prognostic value of 18 F-FDG PET/CT in diffuse large B-cell lymphoma treated with a risk-adapted immunochemotherapy regimen [J ] . J Nucl Med , 2023 , 64 ( 4 ): 536 - 541 .

MENDEVILLE M S , JANSSEN J , TJITSKE LOS-DE VRIES G , et al . Integrating genetic subtypes with PET scan monitoring to predict outcome in diffuse large B-cell lymphoma [J ] . Nat Commun , 2025 , 16 ( 1 ): 109 .

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AI问答

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The research on the association between genetic alterations of DLBCLs and 18F-FDG PET/CT SUVmax and their clinical significance

DOI：10.19401/j.cnki.1007-3639.2025.06.002

摘要

Abstract

关键词

Keywords

references

The research on the association between genetic alterations of DLBCLs and ¹⁸F-FDG PET/CT SUV_max and their clinical significance