CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Association between p16(INK4A) expression and a treatment response to CDK4/6 inhibitor in advanced breast carcinoma.
Association between p16(INK4A) expression and a treatment response to CDK4/6 inhibitor in advanced breast carcinoma.
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我们的研究表明,肿瘤细胞中 p16 表达与晚期乳腺癌对 CDK4/6i 的不良治疗反应显著相关。p16 表达模式作为 CDK4/6i 预测生物标志物的临床意义值得进一步研究。
内分泌治疗联合细胞周期蛋白依赖性激酶4和6抑制剂(1)已被批准用于激素受体阳性、人表皮生长因子受体2(HER2)阴性乳腺癌患者。已知p16-CDK4/6-cyclin D1轴调控细胞周期的S期。我们研究了晚期乳腺癌中p16表达与CDK4/6i治疗反应之间的关联。
研究纳入了2019年至2024年间诊断为浸润性乳腺癌且其肿瘤接受了基于下一代测序(NGS)分析的患者。通过免疫组织化学方法评估浸润性癌内肿瘤细胞和基质细胞中p16的表达。在肿瘤细胞中,p16表达被亚分类为细胞质(TC)、细胞核(TN)或细胞质和细胞核染色(TCN)。在基质细胞中,p16表达在肿瘤相关成纤维细胞(TAF)和肿瘤浸润免疫细胞(TILs)的任何细胞区室中进行评估。
在35例病例中,p16-TC、-TN和-TCN与CDK4/6i治疗期间的疾病进展显著相关。p16-TC与疾病进展之间的正相关关系在24例未接受过CDK4/6i治疗的肿瘤中依然存在。相反,TAF中p16表达的肿瘤显示出比p16-TAF阴性肿瘤数值上更高的缓解率。我们还观察到p16-TC表达与淋巴结转移之间存在显著关联。
Patients diagnosed with invasive breast carcinoma between 2019 and 2024 whose tumors underwent next-generation sequencing (NGS) based analysis were identified. The expression of p16 was assessed in tumor cells and stromal cells within the invasive carcinoma by immunohistochemistry. In tumor cells, p16 expression was subclassified as cytoplasmic (TC), nuclear (TN), or cytoplasmic and nuclear staining (TCN). In stromal cells, p16 expression was assessed in tumor-associated fibroblasts (TAF) and tumor-infiltrating immune cells (TILs) in any cellular compartment.
Among the 35 cases, p16-TC, -TN, and -TCN were significantly associated with disease progression during CDK4/6i therapy. The positive association between p16-TC and progressive disease remained in the 24 CDK4/6i-treatment naïve tumors. In contrast, the tumors with p16 expression in TAF showed a numerically higher response rate than the p16-TAF-negative ones. We also observed a significant association between p16-TC expression and lymph node metastasis.
Our study demonstrated a significant association between p16 expression in tumor cells and an unfavorable therapeutic response to CDK4/6i in advanced breast carcinoma. The clinical significance of p16 expression patterns as a predictive biomarker for CDK4/6i deserves further investigation.
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