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:The impact of circWWC3 on neoadjuvant therapy for triple-negative breast cancer and the construction of a nomogram for predicting pathological complete response after neoadjuvant therapy.
The impact of circWWC3 on neoadjuvant therapy for triple-negative breast cancer and the construction of a nomogram for predicting pathological complete response after neoadjuvant therapy.
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circWWC3 表达水平升高是影响实现 pCR 可能性的独立危险因素。整合 circWWC3 表达与病理和影像学参数的预测模型,在准确预测 TNBC 患者 pCR 概率方面表现出稳健的能力。
新辅助治疗(NAT)新策略的引入显著提高了三阴性乳腺癌(TNBC)患者的病理完全缓解(pCR)率。然而,由于肿瘤异质性,部分患者仍面临治疗效果不佳、早期复发、转移甚至死亡。因此,识别新的分子靶点以实现精准治疗,并开发pCR预测模型以促进个体化治疗方案的制定,至关重要。
我们开展了一项研究,纳入接受NAT的TNBC患者队列,收集临床病理指标、MRI参数及病理缓解结局数据。评估乳腺癌组织中基线circRNA WWC3(circWWC3)的表达水平,并分析其表达与临床病理指标及病理反应的关系。构建并验证了用于预测TNBC pCR的列线图。
2020年1月至2023年12月,共205例患者纳入最终分析。总病理完全缓解(tpCR,定义为ypT0/is且ypN0)率为51.7%。circWWC3在细胞质中高表达,在所有分析的癌组织中表达率为79%。circWWC3高表达与T2分期、N1状态、Ki-67水平大于30%以及TIL(肿瘤浸润淋巴细胞)(TILs)中高度浸润呈正相关(p < 0.05)。此外,新辅助治疗两周期后乳腺MRI表观扩散系数变化率(ΔADC 0-2 %)大于24.53%也显著相关(p < 0.05)。circWWC3高表达的患者更可能达到pCR。单因素和多因素回归分析确定TILs、ΔADC 0-2 %和circWWC3为构建pCR预测列线图的关键变量。该模型表现出良好的区分度、校准度和临床适用性。
The introduction of novel strategies for neoadjuvant therapy (NAT) has significantly enhanced the rate of pathological complete response (pCR) in patients with triple-negative breast cancer (TNBC). However, due to tumor heterogeneity, some patients continue to experience poor treatment efficacy, early recurrence, metastasis, and even mortality. Therefore, it is crucial to identify new molecular targets for precise treatment and to develop predictive models for pCR to facilitate tailored therapeutic approaches.
We conducted a study involving a cohort of TNBC patients who underwent NAT, collecting data on clinicopathological indicators, MRI parameters, and pathological remission outcomes. The expression levels of baseline circular RNA WWC3 (circWWC3) in breast cancer tissue were assessed, and the relationship between its expression and clinicopathological indicators as well as pathological response was analyzed. A nomogram for predicting pCR in TNBC was developed and subsequently validated.
From January 2020 to December 2023, a total of 205 patients were included in the final analysis. The rate of total pathological complete response (tpCR), defined as ypT0/is and ypN0, was observed to be 51.7%. CircWWC3 was found to be highly expressed in the cytoplasm, with an expression rate of 79% among all analyzed cancerous tissues. The elevated expression of circWWC3 was positively correlated with T2 stage, N1 status, Ki-67 levels greater than 30%, and moderate to high infiltration of tumor-infiltrating lymphocytes (TILs) ( p < 0.05). Additionally, a change rate in the apparent diffusion coefficient (ADC) of breast MRI after two cycles of neoadjuvant therapy (ΔADC 0-2 %) greater than 24.53% was significantly associated ( p < 0.05). Patients exhibiting high levels of circWWC3 expression were more likely to achieve pCR. Univariate and multivariate regression analyses identified TILs, ΔADC 0-2 %, and circWWC3 as key variables for constructing a predictive nomogram for pCR. This model demonstrated strong discrimination, calibration, and clinical applicability.
Elevated expression levels of circWWC3 serve as an independent risk factor influencing the likelihood of achieving a pCR. A predictive model that integrates circWWC3 expression alongside pathological and imaging parameters demonstrates a robust capacity to accurately forecast the probability of pCR in patients diagnosed with TNBC.
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