Profiling heterogenous sizes of circulating tumor microemboli to track therapeutic resistance and prognosis in advanced gastric cancer.
Profiling heterogenous sizes of circulating tumor microemboli to track therapeutic resistance and prognosis in advanced gastric cancer.
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分析循环肿瘤微栓子大小的异质性，以追踪晚期胃癌的治疗耐药性和预后。
DOI：
10.1007/s13577-021-00568-2
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发表时间：
2021-09
期刊：
影响因子：
4.3
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Chen Y;Yuan J;Li Y;Li X;Yang Y;Li J;Li Y;Shen L
由≥ 2个循环肿瘤细胞（CTC）聚集的循环肿瘤微栓子（CTM）比单个CTC更具迁移性。除了被认为是肿瘤迁移的分子特征的可塑性之外，CTM还具有高尺寸异质性。因此，本研究使用预先建立的表面分子非依赖性减影富集（SE）-iFISH策略系统地研究了114例晚期胃癌（GC）患者中CTM的异质性大小及其与治疗耐药的关系。在33.3%的GC患者中治疗前检测到的CTM可以在另外34.78%的化疗/靶向治疗患者中进一步形成。CTM的存在与肝转移以及较高的CTC水平（≥ 5/6 mL）相关。GC-CTM的进一步基于尺寸的分析显示，具有2个CTC的CTM（CTM 2）是优势亚型，占所有检测到的GC-CTM的50.0%。然而，具有3-4个CTC的CTM（CTM 3 -4）与化学/靶向治疗抗性和较差的预后特异性相关。CTM 3 -4/6 mL ≥ 1的患者的中位无进展生存期和中位总生存期较短。与在治疗前和治疗后均可检测到的CTM 2和CTM 3 -4不同，仅在4例HER 2 + GC患者中在治疗期间检测到较大聚集的CTM≥5（CTM ≥ 5个CTC），其中3例发生肝转移。所获得的结果表明，GC-CTM的簇大小应在化疗/靶向耐药或转移监测方面动态分析超过治疗前全CTM计数。GC-CTM 3 -4可能是治疗耐药的潜在指标，而GC-CTM≥5的动态存在意味着HER 2 + GC患者的肝转移。
Circulating tumor microemboli (CTM) aggregated by ≥ 2 circulating tumor cells (CTCs) are more migratory than single CTCs. Aside from the plasticity in their molecular characteristics, which have been considered tumor migration, CTM also possesses high size heterogeneity. This study, therefore, systematically investigated the heterogeneous sizes of CTM and their involvement in therapeutic resistance in 114 patients with advanced gastric cancer (GC) using a pre-established surface molecule-independent subtraction enrichment (SE)-iFISH strategy. CTM, which was pre-therapeutically detected in 33.3% of GC patients, can further form in another 34.78% of patients following chemo-/targeted therapies. The presence of CTM is relevant to liver metastasis as well as higher CTC levels (≥ 5/6 mL). Further size-based profiling of GC-CTM revealed that CTM with 2 CTCs (CTM2) was the dominant subtype, accounting for 50.0% of all detected GC-CTMs. However, CTM with 3–4 CTCs (CTM3–4) specifically associates with chemo-/targeted therapeutic resistance and inferior prognosis. Patients with ≥ 1 CTM3–4/6 mL have shorter median progression-free survival and median overall survival. Unlike CTM2 and CTM3–4, which are detectable in pre-therapy and post-therapy, larger aggregated CTM≥5 (CTM with ≥ 5 CTCs) was only intra-therapeutically detected in four HER2+ GC patients, of which three experienced liver metastases. Obtained results suggested that the cluster size of GC-CTM should be dynamically profiled beyond pre-therapeutic whole CTM enumeration in terms of chemo-/targeted resistance or metastasis monitoring. GC-CTM3–4 could be a potential indicator of therapeutic resistance, while the dynamic presence of GC-CTM≥5 implies liver metastasis in HER2+ GC patients.
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影响因子：
28.2
作者：
Liu X;Taftaf R;Kawaguchi M;Chang YF;Chen W;Entenberg D;Zhang Y;Gerratana L;Huang S;Patel DB;Tsui E;Adorno-Cruz V;Chirieleison SM;Cao Y;Harney AS;Patel S;Patsialou A;Shen Y;Avril S;Gilmore HL;Lathia JD;Abbott DW;Cristofanilli M;Condeelis JS;Liu H
通讯作者：
Liu H
影响因子：
11.2
作者：
Bocci, Federico;Jolly, Mohit Kumar;Onuchic, Jose Nelson
通讯作者：
Onuchic, Jose Nelson
DOI：
10.1073/pnas.1524448113
发表时间：
2016-05-03
影响因子：
11.1
作者：
Au, Sam H.;Storey, Brian D.;Toner, Mehmet
通讯作者：
Toner, Mehmet
影响因子：
11.5
作者：
Li, Yilin;Zhang, Xiaotian;Shen, Lin
通讯作者：
Shen, Lin
影响因子：
9.7
作者：
Wang, Liang;Li, Yilin;Dong, Jiahong
通讯作者：
Dong, Jiahong