阑尾源性腹膜假性黏液瘤分子特征对预后的影响

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-02-09 DOI:10.1016/j.tranon.2025.102279

Ruiqing Ma , Guojun Li , Yingjiang Ye , Lei Liang , Chong Wang , Haipeng Zhou , Pu Zhang , Lubiao An , Guanjun Shi , Qian Chen , Hongbin Xu , Zhidong Gao

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引用次数: 0

摘要

腹膜假性黏液瘤（PMP）是一种极其罕见的疾病，其特征是腹膜中黏液性腹水和植入物的进行性积累。我们研究了对细胞减少手术（CRS）或腹腔热化疗（HIPEC）反应的预后价值，并利用基因组特征剖析了潜在的有益靶向治疗。方法对81例PMP患者的组织标本和匹配的白细胞进行全外显子组测序（WES）。该研究调查了突变特征、分析及其与无进展生存期（PFS）和总生存期（OS）的相关性。结果签名3 （HRD）和签名15 （dMMR）占主导地位。以特征4为特征的NMF集群1预后较差。p53和TGF-β信号通路可能分别是OS和PFS恶化的危险因素。muc16突变患者的PFS （P = 0.016）和OS （P = 0.004）较野生型患者差。肿瘤突变负荷（TMB）患者；1（P = 0.026）或TP53 （P = 0.006）或SMAD4 （P = 0.013）的改变与TMB和lt患者相比，OS明显更差；1或正常基因。同源重组缺陷（HRD）阳性（P = 0.003）或TGFBR2改变（P = 0.037）的患者与各自的对照组相比，PFS更差。此外，NMF cluster1 （P = 0.020）、TP53 （P = 0.004）和MUC16 （P = 0.013）被确定为OS的独立预后因素，而HRD状态（P = 0.003）是PMP中PFS的独立预测因素。结论该研究表明，基因组谱分析可以作为鉴定PMP预后标志物的有力工具。已确定的基因组突变和信号通路为靶向治疗提供了新的途径。

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Prognosis conferred by molecular features of appendix-derived Pseudomyxoma Peritonei

Introduction

Pseudomyxoma Peritonei (PMP) is an extremely rare disease characterized by progressive accumulation of mucinous ascites and implants in the peritoneum. We investigated the prognostic value for response to cytoreductive surgery (CRS) or hyperthermic intraperitoneal chemotherapy (HIPEC) and dissected potential beneficial targeted therapy utilizing genomic characteristics.

Methods

Whole-exome sequencing (WES) was performed on tissue specimens and matched white blood cells from 81 patients with PMP. The study investigated mutational signatures, profiling, and their correlation with progression-free survival (PFS) and overall survival (OS).

Results

Signature 3 (HRD) and signature 15 (dMMR) were dominant. NMF cluster 1, characterized by signature 4, exhibited a worse prognosis. The p53 and TGF-β signaling pathways may contribute as risk factors for worse OS and PFS, respectively. MUC16-mutated patients had worse PFS (P = 0.016) and OS (P = 0.004) compared to wild-type patients. Patients with tumor mutational burden (TMB) > 1(P = 0.026) or alterations in TP53 (P = 0.006) or SMAD4 (P = 0.013) had significantly worse OS compared to those with a TMB < 1 or normal genes. Patients with homologous recombination deficiency (HRD) positivity (P = 0.003) or alterations in TGFBR2 (P = 0.037) experienced worse PFS compared to their respective control groups. Furthermore, NMF cluster1 (P = 0.020), TP53 (P = 0.004), and MUC16 (P = 0.013) were identified as independent prognostic factors for OS, while HRD status (P = 0.003) was independent predictors for PFS in PMP.

Conclusions

The study reveals that genomic profiling can serve as a robust tool for identifying prognostic markers in PMP. The identified genomic mutations and signaling pathway offer new avenues for targeted therapies.

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.