Zhang Qian, Xing Wanting, Zhang Jie, Hu Junwen, Qi Lunan, Xiang Bangde
Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People's Republic of China.
Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumors, Ministry of Education, Nanning, People's Republic of China.
Onco Targets Ther. 2021 Mar 2;14:1543-1552. doi: 10.2147/OTT.S298576. eCollection 2021.
The purpose of this study was to elucidate the relationship between cytokeratin 19 (CK19) expression and levels of circulating tumor cells (CTCs) in preoperative peripheral blood of patients with hepatocellular carcinoma (HCC), and the potential influence of that relationship on prognosis.
CanPatrol™ CTC-enrichment technique and in situ hybridization (ISH) were used to enrich and classify CTCs undergoing the epithelial-mesenchymal transition (EMT) from blood samples of 105 HCC patients. CK19 immunohistochemistry staining was performed on HCC tissues and compared with demographic and clinical data.
In total, 27 of 105 (25.7%) HCC patients were CK19-positive. CK19-positive patients had significantly lower median tumor-free survival (TFS) than CK19-negative patients (5 vs 10 months, P = 0.047). In total, 98 (93.3%) patients showed pre-surgery peripheral blood CTCs (range: 0-76, median: 6), and 57 of 105 (54.3%) patients displayed CTC counts ≥6. Furthermore, CK19-positive patients with CTC count ≥6 showed significantly higher percentage than CK19-negative ones (77.8% vs 46.2%, P = 0.004). CK19-positive patients showed a significantly higher proportion of mesenchymal CTCs among CTCs undergoing EMT than CK19-negative patients (mean rank: 62.28 vs 49.79, P = 0.046). We also found that CK19-positive patients with high CTC count showed significantly shorter median tumor-free survival than CK19-negative patients with low CTC count (5 vs 16 months, P = 0.039).
High CTC count and high percentage of mesenchymal CTCs are closely related to the expression of CK19, which is associated with poor prognosis in HCC patients.
本研究旨在阐明细胞角蛋白19（CK19）表达与肝细胞癌（HCC）患者术前外周血中循环肿瘤细胞（CTC）水平之间的关系，以及该关系对预后的潜在影响。
采用CanPatrol™ CTC富集技术和原位杂交（ISH），从105例HCC患者的血样中富集并分类经历上皮-间质转化（EMT）的CTC。对HCC组织进行CK19免疫组化染色，并与人口统计学和临床数据进行比较。
105例HCC患者中共有27例（25.7%）CK19阳性。CK19阳性患者的无瘤生存期（TFS）中位数显著低于CK19阴性患者（5个月对10个月，P = 0.047）。共有98例（93.3%）患者术前外周血中检测到CTC（范围：0 - 76，中位数：6），105例患者中有57例（54.3%）的CTC计数≥6。此外，CTC计数≥6的CK19阳性患者的比例显著高于CK19阴性患者（77.8%对46.2%，P = 0.004）。在经历EMT的CTC中，CK19阳性患者的间充质CTC比例显著高于CK19阴性患者（平均秩次：62.28对49.79，P = 0.046）。我们还发现，CTC计数高的CK19阳性患者的无瘤生存期中位数显著短于CTC计数低的CK19阴性患者（5个月对16个月，P = 0.039）。
高CTC计数和高比例的间充质CTC与CK19表达密切相关，这与HCC患者的不良预后相关。
