当前观察：乳腺导管原位癌分子分类和临床预后的生物标志物

美国斯坦福大学医学院Robert B. West和美国杜克大学医学院E. Shelley Hwang共同合作，近期取得重要工作进展。他们通过对TBCRC 038和RAHBT队列的研究分析，开发出了乳腺导管原位癌的分子分类和临床预后的生物标志物。相关研究结果2022年11月17日在线发表于《癌细胞》杂志上。

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研究人员通过分析542名患者的774个DCIS样本，对DCIS进行多尺度的综合分子谱图分析，患者的中位随访时间为7.3年。患者来自转化乳腺癌研究联合会038（TBCRC 038）和档案乳腺组织资源（RAHBT）。研究人员鉴定出812个与治疗后5年内同侧复发相关的基因，并开发了一个分类器来预测两个队列患者中DCIS或IBC复发的情况。与复发相关的途径包括增殖、免疫反应和代谢。研究人员鉴定了不同的基质表达模式和免疫细胞组成。

这种多尺度方法采用了原位法，生成了一个空间分辨率的乳腺前体图谱，其中的互补模式可以直接与常规病理结果、疾病状态和临床结果进行比较和关联。

据介绍，导管原位癌（DCIS）是浸润性乳腺癌（IBC）最常见的前兆，具有不同的进展倾向。

附：英文原文

Title: Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts

Author: Siri H. Strand, Belén Rivero-Gutiérrez, Kathleen E. Houlahan, Jose A. Seoane, Lorraine M. King, Tyler Risom, Lunden A. Simpson, Sujay Vennam, Aziz Khan, Luis Cisneros, Timothy Hardman, Bryan Harmon, Fergus Couch, Kristalyn Gallagher, Mark Kilgore, Shi Wei, Angela DeMichele, Tari King, Priscilla F. McAuliffe, Julie Nangia, Joanna Lee, Jennifer Tseng, Anna Maria Storniolo, Alastair M. Thompson, Gaorav P. Gupta, Robyn Burns, Deborah J. Veis, Katherine DeSchryver, Chunfang Zhu, Magdalena Matusiak, Jason Wang, Shirley X. Zhu, Jen Tappenden, Daisy Yi Ding, Dadong Zhang, Jingqin Luo, Shu Jiang, Sushama Varma, Lauren Anderson, Cody Straub, Sucheta Srivastava, Christina Curtis, Rob Tibshirani, Robert Michael Angelo, Allison Hall, Kouros Owzar, Kornelia Polyak, Carlo Maley, Jeffrey R. Marks, Graham A. Colditz, E. Shelley Hwang, Robert B. West

Issue&Volume: 2022-11-17

Abstract: Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We perform multiscale, integrated molecular profiling of DCIS with clinical outcomes by analyzing 774 DCIS samples from 542 patients with 7.3 years median follow-up from the Translational Breast Cancer Research Consortium 038 study and the Resource of Archival Breast Tissue cohorts. We identify 812 genes associated with ipsilateral recurrence within 5 years from treatment and develop a classifier that predicts DCIS or IBC recurrence in both cohorts. Pathways associated with recurrence include proliferation, immune response, and metabolism. Distinct stromal expression patterns and immune cell compositions are identified. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.

DOI: 10.1016/j.ccell.2022.10.021

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00512-8

来源：科学网 小柯机器人

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