Wang Hui-Li, Shang Chun-Yu, Hua Wei, Yin Hua, Li Yue, Liang Jun-Heng, Gao Rui, Pan Bi-Hui, Zhang Xin-Yu, Wu Jia-Zhu, Shen Hao-Rui, Wang Li, Li Jian-Yong, Liang Jin-Hua, Xu Wei
Department of Hematology, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
Department of Hematology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
Cancer Res Treat. 2025 Jul 28. doi: 10.4143/crt.2024.1143.
CD58, a ligand of the CD2 receptor on T cells and NK cells, is abnormally expressed in diffuse large B-cell lymphoma (DLBCL). However, data on the value of CD58 mutation (CD58mut) in DLBCL are limited. Here, we aimed to evaluate the characteristics and prognostic value of CD58mut in DLBCL patients.
The available clinical information and corresponding mutation data of DLBCL were obtained from published articles. Ultimately, 3025 DLBCL patients in published cohorts were enrolled in the final analysis. Among the 202 DLBCL patients in the Jiangsu Province Hospital (JSPH) cohort, all tumor tissue samples were collected to perform NGS and gene expression were analyzed via RNA-seq.
We found that 8.2% (250/3025) of patients were CD58mut in integrated cohort, whereas 11.3% (23/202) in JSPH cohort. CD58mut patients exhibit inferior progression-free survival (PFS) (the integrated cohort: HR=0.96,95% CI:0.77-1.20, p=0.663 the JSPH cohort: HR=1.85,95% CI:0.85-4.04, p=0.052) and overall survival (OS) (the integrated cohort: HR=1.43,95% CI:1.15-1.77, p<0.001; the JSPH cohort: HR=2.40,95% CI:0.83-6.93, p=0.026). A model based on six signature genes (MRO, OXTR, RASL11A, RLN1, SIGLEC1 and PROM2) was constructed via machine learning. To optimize risk stratification and survival prediction for CD58mut patients, biological mechanism of the poorer prognosis in high-risk group may be related to the greater abundance of immunosuppressive cells, especially M2 macrophages.
Our results indicated that CD58mut could serve as a novel prognostic factor for DLBCL patients, and further exploration of personalized treatment strategies for high-risk DLBCL patients based on the risk score model is needed.
CD58是T细胞和NK细胞上CD2受体的配体，在弥漫性大B细胞淋巴瘤（DLBCL）中异常表达。然而，关于DLBCL中CD58突变（CD58mut）价值的数据有限。在此，我们旨在评估DLBCL患者中CD58mut的特征和预后价值。
从已发表的文章中获取DLBCL的可用临床信息和相应的突变数据。最终，将已发表队列中的3025例DLBCL患者纳入最终分析。在江苏省人民医院（JSPH）队列的202例DLBCL患者中，收集所有肿瘤组织样本进行NGS，并通过RNA测序分析基因表达。
我们发现，在综合队列中8.2%（250/3025）的患者存在CD58mut，而在JSPH队列中为11.3%（23/202）。CD58mut患者的无进展生存期（PFS）较差（综合队列：HR = 0.96，95% CI：0.77 - 1.20，p = 0.663；JSPH队列：HR = 1.85，95% CI：0.85 - 4.04，p = 0.052），总生存期（OS）也较差（综合队列：HR = 1.43，95% CI：1.15 - 1.77，p < 0.001；JSPH队列：HR = 2.40，95% CI：0.83 - 6.93，p = 0.026）。通过机器学习构建了一个基于六个特征基因（MRO、OXTR、RASL11A、RLN1、SIGLEC1和PROM2）的模型。为了优化CD58mut患者的风险分层和生存预测，高危组预后较差的生物学机制可能与免疫抑制细胞尤其是M2巨噬细胞的丰度较高有关。
我们的结果表明，CD58mut可作为DLBCL患者的一种新的预后因素，需要基于风险评分模型进一步探索高危DLBCL患者的个性化治疗策略。
