PO.MCB08.01 · 分子与细胞生物学
阿曼乳腺癌队列中跨年龄组治疗反应的转录组预测因子
Transcriptomic predictors of therapy response across age groups in an omani breast cancer cohort
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
乳腺癌（BC）表现出受年龄、内在亚型和治疗诱导的分子重塑影响的深刻异质性。我们进行了分子分析，以识别可预测阿曼BC患者肿瘤生物学、治疗反应和生存结局的转录组生物标志物。
方法：分析了苏丹卡布斯大学医院39例BC患者的存档FFPE组织。使用NanoString Breast Cancer 360检测进行转录组分析，并与临床和病理数据整合。使用Spearman相关性评估年龄与生物特征之间的关系。构建决策树模型以识别以下方面的分子决定因素：(i) 跨年龄组的治疗分配，(ii) 病理完全缓解（pCR）与部分缓解（pPR），以及 (iii) 生存。
结果：年龄显示出强烈的分子模式：较年长患者具有更高的ESR1、AR、PTEN、基质和Claudin-Low表达特征，而较年轻患者表现出更高的CD8⁺ T细胞、增殖、HRD、p53和BRCAness评分，与基因组不稳定、免疫活跃的表型一致。在早发性疾病中，ERBB2是主要的治疗分类因子，CDK6和巨噬细胞特征进一步区分内分泌治疗与TNBC化疗；在晚发性肿瘤中，IFN-gamma和SOX2定义了治疗分支，提示存在年龄特异性的免疫和干性程序。在各反应分层中，pCR由高ERBB2和CD8⁺富集的免疫特征驱动。相比之下，pPR以BRCAness和细胞黏附为特征，表明HRD样与黏附驱动的侵袭性之间存在重叠，以及靶向疗法（如trastuzumab）对反应的影响。生存模型反映了这一点，将长期生存与HER2调节和免疫激活联系起来，将非生存与AR和Claudin-Low样状态联系起来。
结论：在这个阿曼队列中，年龄与不同的、情境化的分子程序相关。较年轻患者表现出HER2驱动、HRD富集、高度增殖和免疫活跃的生物学特征，而较年长患者表现出激素受体主导、基质和PTEN保留的表型。所获得的数据表明，将ERBB2变异、免疫指标和HRD样特征整合到中东和北非（MENA）人群未来的风险适应策略中，可考虑用于诊断和治疗目的。
查看英文原文 English abstract
Breast cancer (BC) exhibits profound heterogeneity influenced by age, intrinsic subtypes, and treatment-induced molecular remodeling. We performed molecular analysis to identify transcriptomic biomarkers predictive of tumor biology, treatment response, and survival outcomes in Omani BC patients.
Methods: Archived FFPE tissues from 39 BC patients at Sultan Qaboos University Hospital were analyzed. Transcriptomic profiling using the NanoString Breast Cancer 360 assay was integrated with clinical and pathologic data. Spearman correlations were used to assess the relationships between age and biosignatures. Decision tree models were constructed to identify molecular determinants of (i) treatment allocation across age groups, (ii) pathologic complete response (pCR) versus partial response (pPR), and (iii) survival.
Results: Age showed a strong molecular pattern: older patients had higher ESR1, AR, PTEN, stromal, and Claudin-Low expression signatures, while younger patients exhibited higher CD8⁺ T-cell, proliferation, HRD, p53, and BRCAness scores, consistent with a genomically unstable, immune-active phenotype. In early-onset disease, ERBB2 was the dominant treatment classifier, with CDK6 and macrophage signatures further stratifying endocrine versus TNBC chemotherapy; in late-onset tumors, IFN-gamma and SOX2 defined treatment branches, suggesting age-specific immune and stemness programs. Across response strata, pCR was driven by high ERBB2 and CD8⁺-rich immune signatures. In contrast, pPR was characterized by BRCAness and Cell Adhesion, indicating an overlap between HRD-like and adhesion-driven aggressiveness, as well as the impact of targeted therapies, such as trastuzumab, on response. Survival models mirrored this, linking long-term survival to HER2 modulation and immune activation and non-survival to AR and Claudin-Low-like states.
Conclusions: In this Omani cohort, age is associated with distinct, contextualized molecular programs. Younger patients exhibit HER2-driven, HRD-enriched, highly proliferative and immune-active biology, while older patients show hormone receptor-dominated, stromal and PTEN-preserved phenotypes. The data obtained indicate that integrating ERBB2 variations, immune metrics, and HRD-like signatures into future risk-adapted strategies in Middle East and North Africa (MENA) populations may be considered for diagnostic and treatment purposes.
利益披露 Disclosure
M. Al Dlali, None..
H. El Keraby, None..
H. Zaidom, None..
R. Al ajmi, None..
C. Crozier, None..
J. Bayani, None..
S. A. Adham, None.