PO.TB07.01 · 肿瘤生物学
揭示癌症干细胞标志物与滤泡性淋巴瘤患者生存的关联
Unveiling the association of cancer stem cell markers with survival in follicular lymphoma patients
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：滤泡性淋巴瘤（FL）是第二常见的非霍奇金淋巴瘤亚型，其特征为病程呈迁延的起伏消长。尽管治疗取得了进展，但约半数FL患者在五年内复发并对治疗产生难治性。诸如FL国际预后指数（FLIP）等临床风险因素尚未被用于指导治疗策略的选择。迄今尚无预后标志物供FL患者或医生选择治疗，或理解其治疗耐药及复发进程。在此，我们在组织芯片切片（TMA）中鉴定癌症干细胞（CSC）标志物，并确定它们与FL患者生存的关联。
方法：通过AI软件Deep6和Slicer Dicer在EPIC中构建查询（ICD-10编码：C82.9），鉴定出共105例有可用淋巴结活检蜡块的FL患者。收集了这些FL患者的人口统计学和临床病理特征。将FL患者分为两组：短期生存（少于5年）和长期生存（超过20年）的FL患者。收集了59例FL患者淋巴结活检的FFPE蜡块，用于制作组织芯片切片（TMA）。进行了FL细胞（CD20）和CSC（ABCG2、Ki67和OCT3/4）的H&E染色和IHC染色。采用HALO®软件分析CSC频率。采用GraphPad Prism 9进行统计分析。双侧p值<0.05被认为具有统计学意义。
结果：在59例FL患者中，26例（44.1%）为短期生存，33例（55.9%）FL患者为长期生存。尽管短期和长期生存组之间CD20+细胞的频率无差异，但与长期组相比，短期生存组中单一CSC标志物（ABCG2、Ki67或OCT3/4）以及CSC组合标志物（ABCG2+、Ki67+、OCT3/4+）的频率显著增加（p值<0.05）。
结论：我们的结果揭示了表型上不同的CSC标志物，它们独立于现有预后标志物，并与FL患者的短期生存相关，表明它们在预测FL患者结局方面的预后价值。评估CSC标志物可能有助于识别高危个体并指导FL患者的个性化治疗。
查看英文原文 English abstract
Background: Follicular lymphoma (FL) is the second most prevalent subtype of non-Hodgkin's lymphoma characterized by a protracted waxing and waning clinical course. Despite advances in treatments, about half of FL patients experience relapse within five years and become refractory to treatment. Clinical risk factors such as FL International Prognostic Index (FLIP) have not been used to guide the selection of treatment strategies. So far there are no prognostic markers for FL patients or physicians to select their treatment or understand their treatment resistance as well as relapse courses. Here we identified the cancer stem cell (CSC) markers in tissue microarray slides (TMA) and determined their association with FL patient survival.
Methods: Total 105 FL pts with available lymph node biopsy blocks were identified by AI software Deep6 and Slicer Dicer for query building in EPIC (ICD-10 code: C82.9). Demographic and clinicopathological characteristics of these FL pts were collected. FL patients were divided in two groups: FL pts with short-term survival (less than 5 years) and long-term survival (more than 20 years). FFPE blocks from 59 FL pts lymph node biopsies were collected and used to create tissue microarray slides (TMA). H&E staining and IHC staining of FL cells (CD20) and CSCs (ABCG2, Ki67, and OCT3/4) were performed. Frequency of CSCs was analyzed using HALO® software. statistical analyses were performed using GraphPad prism 9. Two-sided p values <0.05 were considered statistically significance.
Results: Among 59 FL patients, 26 (44.1%) pts were short-term survival, and 33 (55.9%) FL pts were long-term survival. Although no difference in the frequencies of CD20+ cells between the short-term and long-term survival groups, significant increases in the frequencies of single CSC markers (ABCG2, Ki67, or OCT3/4) as well as CSC combination markers (ABCG2+, Ki67+, OCT3/4+) were found in the short-term survival group compared to the long-term group (p values <0.05).
Conclusion: Our results unveil phenotypically distinct CSC markers that are independence of existing prognostic markers and associated with short-term survival in FL pts, indicating their prognostic value in predicting FL patients' outcome. Evaluation of CSC markers may aid in identifying high-risk individuals and guiding personalized treatment in FL patients.
利益披露 Disclosure
X. Zhang, None..
O. White, None..
D. Ashley, None..
B. Chung, None.