Genetic alterations and their prognostic impact in marginal zone lymphoma: a meta-analysis

Annals of Hematology https://doi.org/10.1007/s00277-024-06175-z REVIEW Genetic alterations and their prognostic impact in marginal zone lymphoma: a meta-analysis Xijing Li1 · Yang Lin2 · Licai An2 Received: 16 August 2024 / Accepted: 28 December 2024 © The Author(s) 2024 Abstract This meta-analysis aimed to assess the impact of genetic mutations, particularly in the NOTCH2 and TNFAIP3 genes, on the prognostic outcomes of Marginal Zone Lymphoma (MZL) patients. Databases, including PubMed, Embase, and Cochrane Library, were explored up to October 2023. A total of 11 studies encompassing 2,314 records were included. Outcome measures were 5-year overall survival rates (OSR), progression-free survival rates (PFSR), and tumor progression rates (TPR). NOTCH2 and TNFAIP3 mutations were prominently identified across studies. In splenic MZL (SMZL) patients with NOTCH2 mutations, there was a significant decrease in the 5-year OSR (SMD: -11.11, 95% CI: -13.39 to -8.84, P < 0.01) and PFSR (SMD: -23.49, 95% CI: -28.85 to -18.14, P < 0.01). Similarly, TNFAIP3 mutations in SMZL patients demonstrated diminished 5-year OSR (SMD: -14.78, 95% CI: -18.01 to -11.56, P < 0.01) and PFSR (SMD: -21.06, 95% CI: -27.13 to -14.98, P < 0.01). For ocular adnexal MZL (OA-MZL) patients with NOTCH2 mutations, the 5-year OSR significantly declined (SMD: -23.40, 95% CI: -28.87 to -17.93, P < 0.01). Genetic mutations, notably in NOTCH2 and TNFAIP3 genes, have discernable negative implications on the prognosis of MZL patients. Recognizing these genetic markers can guide more personalized therapeutic interventions and inform clinical prognosis. Keywords Genetic alterations · Prognostic impact · Marginal zone lymphoma · Meta-analysis Introduction Marginal Zone Lymphoma (MZL) stands as a heterogeneous group of non-Hodgkin lymphomas originating from the marginal zone B-cells present within lymph nodes and other lymphatic tissues [1]. MZL is taxonomically divided into three distinct entities, namely extranodal MZL of mucosa-associated lymphoid tissue (MALT), nodal marginal zone lymphoma (NMZL), and splenic marginal zone lymphoma (SMZL). Each of these exhibits’ unique clinical presentations and genetic features [2]. Xijing Li and Yang Lin contributed equally to this work. Licai An 1 Department of Pathology, Yantaishan Hospital, Yantai City, Shandong 264003, China 2 Department of Hematology, Yantai Yuhuangding Hospital, No. 20 Yudong Road, Zhifu District, Yantai City, Shandong 264000, China With advancements in high-throughput sequencing technologies, we have delved deeper into the genetic alterations associated with MZL. These genetic changes encompass mutations, copy number variations, and epigenetic modifications, all of which play pivotal roles in the pathogenesis of MZL [3]. However, the repercussions of these genetic alterations on the prognosis of MZL remain a partially uncharted domain. Emerging studies have started to unveil the relationships between specific genetic alterations and the prognosis of MZL. For instance, mutations in certain genes have been linked to poorer outcomes, while alterations in others portend a more favorable prognosis [4, 5]. Gene expression analysis has further demarcated different subgroups within MZL, each with divergent prognostic outcomes [4]. A study focusing on NMZL highlighted a rare case wherein a patient exhibited atypical chylous effusions, underscoring the clinical diversity within MZL and signifying the need for deeper comprehension of its association with genetic alterations [6]. Specifically, targetable mutations such as those in the NOTCH2 and TNFAIP3 genes have been identified in MZL, offering opportunities for targeted therapies [7]. Moreover, 13 Annals of Hematology recent breakthroughs have recognized the significance of mutations in the KLF2 gene, further underscoring the genetic complexity and therapeutic potential for MZL [8]. In this meta-analysis, we aim to synthesize recent research advancements to discern the implications of genetic alterations on the prognosis of MZL. By doing so, we aspire to pave the way for more targeted and individualized therapeutic strategies for MZL patients. Methods Search strategy To methodically assess genetic alterations and their prognostic ramifications in MZL, we designed an exhaustive and rigorous search strategy. With PRISMA guidelines as our beacon, prominent databases such as PubMed, Embase, the Cochrane Library, and Google Scholar underwent in-depth exploration. The keyword cluster comprised terms like ‘Marginal Zone Lymphoma’, ‘genetic alterations’, ‘prognosis’, ‘epigenetic modifications’, and ‘mutation implications’. The search was anchored to harness studies up to October 2023, with an exclusive preference for English language publications. An initial distillation was achieved by skimming through titles and abstracts, which subsequently paved the way for a deeper analysis of relevant articles’ full content. Criteria for study inclusion and exclusion Our focus remained steadfast on studies that illuminated the relationship between genetic alterations and prognosis within the context of Marginal Zone Lymphoma. Randomized controlled trials, especially those shedding light on distinct genetic modifications and their consequent clinical outcomes, were particularly sought after. We sidestepped studies devoid of a pronounced focus on MZL genetic alterations, as well as genres such as reviews, case observations, and commentaries. The initial evaluation was confined to abstracts and titles, but qualifying studies were subjected to a more thorough inspection. In instances of selection discordance, mutual consultations facilitated a consensus. Data aggregation To harness the full spectrum of relevant insights, we adopted a structured data compilation regimen. This entailed recording pivotal details like the principal investigator, study locale, publication year, and the methodological blueprint. Demographic parameters, particularly age group delineations, were meticulously logged. Furthermore, we paid 13 close attention to the interventions explored, the outcomes presented, and the nuanced impact of specific genetic deviations on MZL prognosis. Statistical analysis Grounding our analytical pursuits was the Review Manager (RevMan) software, an apt choice given its precision in meta-analytical studies. For continuous data realms, interpretations were based on either the mean difference (MD) or the standardized mean difference (SMD), each accompanied by its 95% confidence intervals (CIs). Dichotomous datasets were deciphered through risk ratio (RR) or odds ratio (OR) metrics, with pertinent 95% CIs. The I² statistic, pivotal in gauging study-to-study variability, was employed, designating a P-value of less than 0.05 as the benchmark for statistical significance. Evaluation of publication bias To shield our findings from potential biases, we relied on the tried-and-tested Cochrane Risk of Bias tool. Each st (...truncated)