基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Digital Whole Slide Image Analysis of Elevated Stromal Content and Extracellular Matrix Protein Expression Predicts Adverse Prognosis in Triple-Negative Breast Cancer.
Digital Whole Slide Image Analysis of Elevated Stromal Content and Extracellular Matrix Protein Expression Predicts Adverse Prognosis in Triple-Negative Breast Cancer.
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三阴性乳腺癌(TNBC)是一种预后差、治疗选择有限的乳腺癌亚型。本研究评估TNBC中基质标志物的预后价值,重点关注全切片图像(WSI)中的肿瘤-基质比(TSR)和总体基质比(OSR),以及组织微阵列(TMA)上I型胶原、III型胶原和fibrillin-1的表达,采用视觉评估和数字图像分析(DIA)两种方法。共纳入101例女性TNBC患者,主要在2005年至2016年间接受手术治疗。
我们发现,高视觉OSR与较差的总生存期(OS)、晚期pN分期、较低的基质TIL(肿瘤浸润淋巴细胞)计数(sTIL)、较低的有丝分裂指数以及患者年龄相关(p < 0.05)。TSR与pN分期和有丝分裂指数存在显著关联(p < 0.01)。I型胶原(>45%)、III型胶原(>30%)和fibrillin-1(>20%)的高表达水平与显著较差的OS(p = 0.004、 p = 0.013和 p = 0.005)和无进展生存期(PFS)(p = 0.028、 p = 0.025和 p = 0.002)相关,并在mRNA水平得到验证。
我们的结果强调了基质特征在促进肿瘤进展和转移中的重要性,以及靶向细胞外基质(ECM)成分可能提供新的治疗策略。此外,DIA在评估TSR、OSR和免疫检测的基质标志物方面比传统视觉检查更准确、更客观。
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis and limited treatment options.
This study evaluates the prognostic value of stromal markers in TNBC, focusing on the tumor-stroma ratio (TSR) and overall stroma ratio (OSR) in whole slide images (WSI), as well as the expression of type-I collagen, type-III collagen, and fibrillin-1 on tissue microarrays (TMAs), using both visual assessment and digital image analysis (DIA). A total of 101 female TNBC patients, primarily treated with surgery between 2005 and 2016, were included.
We found that high visual OSR correlates with worse overall survival (OS), advanced pN categories, lower stromal tumor-infiltrating lymphocyte count (sTIL), lower mitotic index, and patient age ( p < 0. 05). TSR showed significant connections to the pN category and mitotic index ( p < 0. 01).
High expression levels of type-I collagen (>45%), type-III collagen (>30%), and fibrillin-1 (>20%) were linked to significantly worse OS ( p = 0. 004, p = 0. 013, and p = 0. 005, respectively) and progression-free survival (PFS) ( p = 0. 028, p = 0. 025, and p = 0. 002, respectively), validated at the mRNA level.
Our results highlight the importance of stromal characteristics in promoting tumor progression and metastasis and that targeting extracellular matrix (ECM) components may offer novel therapeutic strategies.
Furthermore, DIA can be more accurate and objective in evaluating TSR, OSR, and immunodetected stromal markers than traditional visual examination.
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