Clin Cancer Res:多重免疫荧光鉴定前列腺癌单细胞水平的PI3K通路激活

2020-10-04 星云 MedSci原创

鉴别高PI3K通路活性的癌症对于PI3K抑制剂的治疗选择和临床试验的准入资格至关重要。肿瘤信号通路活性的评估需要考虑肿瘤内异质性和多重调控点。

鉴别高PI3K通路活性的癌症对于PI3K抑制剂的治疗选择和临床试验的准入资格至关重要。肿瘤信号通路活性的评估需要考虑肿瘤内异质性和多重调控点。

Stopsack等建立了一种新的、机械化的方法,通过使用自定义算法量化单细胞-水平多重免疫荧光来评估肿瘤信号通路。在一项概念验证研究中,研究人员将两项前瞻性队列研究的原发性前列腺癌患者的石蜡包埋(FFPE)组织染色进行分析验证。以PTEN、stathmin(一种19KDa磷蛋白)和磷-S6作为PI3K活化的量化指标,以得出细胞级PI3K分数。

在1001名男性中,共评估了988254个肿瘤细胞(中位数 743个细胞/肿瘤)。PI3K在病理学家评估的PTEN丢失、Gleason等级较高以及新验证的PI3K转录特征的肿瘤中得分较高。无监督的机器学习方法可得到类似的群集。在细胞级PI3K得分中,肿瘤内异质性较高。在长期随访(中位时间 15.3年)中,PI3K活化最高四分位数患者的转移进展和前列腺癌死亡率是最低四分位数患者的两倍(危险比 2.04;95% CI 1.13-3.68)。

综上,本研究采用以通路为中心的新方法,量化FFPE组织中的单细胞水平免疫荧光,来识别PI3K通路激活的前列腺肿瘤;这类肿瘤更具侵袭性,并且可能响应通路抑制剂的疗效。

原始出处:

Konrad H. Stopsack, et al. Multiplex Immunofluorescence in Formalin-Fixed Paraffin-Embedded Tumor Tissue to Identify Single-Cell–Level PI3K Pathway Activation. Clin Cancer Res. October 1 2020 DOI:10.1158/1078-0432.CCR-20-2000

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    2020-10-04 misszhang

    前列腺癌相关研究,学习了,谢谢梅斯

    0

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