Application of a novel microscopic technique for quantifying CA125 binding to circulating mononuclear cells in longitudinal specimens during treatment for ovarian cancer.
Application of a novel microscopic technique for quantifying CA125 binding to circulating mononuclear cells in longitudinal specimens during treatment for ovarian cancer.
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DOI：
10.1186/s13048-022-00957-7
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发表时间：
2022-02-26
影响因子：
4
通讯作者：
Cramer DW
中科院分区：
文献类型：
--
作者：
Lakatos K;González G;Hoballah J;Brooker J;Jeong S;Evans C;Krauledat P;Hansen WP;Elias KM;Patankar M;Fülöp V;Konstantinopoulos PA;Cramer DW
血清CA125是人粘蛋白16(MUC16)的抗原片段，用于监测上皮性卵巢癌(EOC)的临床进展情况。然而，MUC16不只是一个反映肿瘤负担的被动标记物，它可能通过与免疫细胞结合并改变其肿瘤反应而发挥更积极的作用。我们开发了一种研究工具来测量MUC16与外周血单个核细胞(PBMC)亚型表面的结合，并使用从一名接受高级别浆液性卵巢癌治疗的妇女连续收集的标本来测试其研究价值。将冻存的PBMC与抗CA125抗体标记的血浆金纳米粒(PNPs)混合，检测细胞表面MUC16结合情况，并用荧光染色识别B细胞、NK细胞、NK-T细胞、T细胞和单核细胞。从3D暗场图像中，应用计算机算法计数PNP结合和荧光显微镜以识别细胞谱系。通过将泊松分布与相似细胞类型的PNP计数进行拟合来确定MUC16的平均结合。MUC16与细胞类型的结合与治疗细节、CA125水平和全血细胞计数(CBC)数据相关。在21个月的时间里，单核细胞的MUC16结合率最高，与血清CA125呈正相关，与循环单核细胞和淋巴细胞计数呈负相关。PNP与NK细胞结合的波动与化疗类型和手术事件有暂时的相关性。与NK-T细胞结合的MUC16水平与与T细胞和NK-T细胞结合的MUC16水平呈正相关，与循环血小板呈负相关。可以使用暗场显微镜和荧光显微镜来评估冷冻保存的PBMC细胞类型之间的MUC16结合。不同细胞类型的结合水平与血清CA125、CBC数据和治疗细节之间的相关性表明，新技术可能为卵巢癌的临床过程提供新的见解。
Measurement of serum CA125, an antigenic fragment of human mucin 16 (MUC16), is used to monitor the clinical progression of epithelial ovarian cancer (EOC). However, rather than simply a passive marker reflecting tumor burden, MUC16 may have a more active role by binding to immune cells and altering their tumor response. We developed a research tool to measure MUC16-binding to the surfaces of peripheral blood mononuclear cell (PBMC) subtypes and tested its research value using specimens collected serially from a woman being treated for high grade serous EOC. Cryopreserved PBMCs were mixed with anti-CA125 antibody-labeled plasmonic gold nanoparticles (PNPs) to detect cell surface MUC16-binding along with fluorescent stains to identify B cells, NK cells, NK-T cells, T cells, and monocytes. From 3D darkfield images, a computer algorithm was applied to enumerate PNP-binding and fluorescence microscopy to identify cell lineage. Average MUC16-binding was determined by fitting a Poisson distribution to PNP-counts across similar cell types. MUC16-binding to cell types was correlated with treatment details, CA125 levels, and complete blood count (CBC) data. Over a 21-month period, monocytes had the highest level of MUC16-binding which was positively correlated with serum CA125 and inversely correlated with circulating monocyte and lymphocyte counts. Fluctuations of PNP-binding to NK cells were associated temporally with types of chemotherapy and surgical events. Levels of MUC16 bound to NK cells were positively correlated with levels of MUC16 bound to T and NK-T cells and inversely correlated with circulating platelets. Assessment of MUC16-binding among cryopreserved PBMC cell types can be accomplished using darkfield and fluorescence microscopy. Correlations observed between level of binding by cell type with serum CA125, CBC data, and treatment details suggest that the new techniques may offer novel insights into EOC’s clinical course.
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影响因子：
6.4
作者：
Belisle, Jennifer A.;Gubbels, Jennifer A. A.;Patankar, Manish S.
通讯作者：
Patankar, Manish S.
影响因子：
4.4
作者：
Bae, Jooeun;Munshi, Aditya;Munshi, Nikhil C.
通讯作者：
Munshi, Nikhil C.
影响因子：
5.2
作者：
González G;Lakatos K;Hoballah J;Fritz-Klaus R;Al-Johani L;Brooker J;Jeong S;Evans CL;Krauledat P;Cramer DW;Hoffman RA;Hansen WP;Patankar MS
通讯作者：
Patankar MS
影响因子：
15.9
作者：
BAST, RC;FEENEY, M;KNAPP, RC
通讯作者：
KNAPP, RC
影响因子：
37.3
作者：
Gubbels JA;Felder M;Horibata S;Belisle JA;Kapur A;Holden H;Petrie S;Migneault M;Rancourt C;Connor JP;Patankar MS
通讯作者：
Patankar MS