Debnath Partha, Dalal Kruti, Dalal Bhavik, Athalye Shreyasi, Chandnani Sanjay, Jain Shubham, Shukla Akash, Rathi Pravin, Shankarkumar Aruna
Department of Gastroenterology, Topiwala National Medical College and BYL Ch Hospital, Dr. A.L Nair Road, Mumbai 400 008, Maharashtra, India.
Transfusion Transmitted Diseases Department, National Institute of Immunohaematology, 13th Floor, New Multi-storeyed Bldg, KEM Hospital Campus, Parel, Mumbai 400 012, Maharashtra, India.
J Clin Exp Hepatol. 2023 Jul-Aug;13(4):608-617. doi: 10.1016/j.jceh.2023.02.002. Epub 2023 Feb 10.
Hepatocellular carcinoma (HCC) is asymptomatic at an early stage which delays its timely diagnosis and treatment. Circulating tumor cells (CTCs), derived from a primary or secondary tumor, may help in the management of HCC. Here, we evaluate and characterize CTCs in liver disease patients.
In total, 65 patients, categorized into liver cirrhosis (LC) (n = 30) and HCC (n = 35), were enrolled. Using ImagestreamX MkII imaging flow cytometer, CTCs were detected and characterized using biomarker expression of EpCAM, CK, AFP, CD45, and DRAQ5 in LC and HCC patients.
CTCs were detected in 33/35 (94%) HCC patients and in 28/30 (93%) LC patients. In the HCC group, the number of biomarker-positive CTCs was higher in BCLC stage D when compared with others. EpCAM + CK was the most expressed biomarker on CTCs in LC versus HCC (83.3% vs. 77.14%), followed by AFP (80% vs. 65.71%), EpCAM (30% vs. 28.57%), and CK (16.6% vs. 14.28%). The EpCAM cell area was significantly associated ( value = 0.031) with the CTC-positive status. The combination biomarker expression of CTCs cell area (EpCAM, CK, and AFP) performed well with the area under the curve of 0.92, high sensitivity, and specificity in detecting early-stage and AFP-negative HCC as well as in AFP-negative LC cases.
Enumeration and cell area of CTCs may be used as a biomarker for early detection of HCC and guiding treatment.
肝细胞癌（HCC）在早期通常没有症状，这会延误其及时诊断和治疗。源自原发性或继发性肿瘤的循环肿瘤细胞（CTC）可能有助于HCC的管理。在此，我们对肝病患者的CTC进行评估和特征分析。
总共纳入65例患者，分为肝硬化（LC）组（n = 30）和HCC组（n = 35）。使用ImagestreamX MkII成像流式细胞仪，通过检测LC和HCC患者中EpCAM、CK、AFP、CD45和DRAQ5的生物标志物表达来检测和表征CTC。
在35例HCC患者中有33例（94%）检测到CTC，在30例LC患者中有28例（93%）检测到CTC。在HCC组中，与其他阶段相比，BCLC D期的生物标志物阳性CTC数量更高。在LC与HCC中，EpCAM + CK是CTC上表达最多的生物标志物（83.3%对77.14%），其次是AFP（80%对65.71%）、EpCAM（30%对28.57%）和CK（16.6%对14.28%）。EpCAM细胞面积与CTC阳性状态显著相关（P值 = 0.031）。CTC细胞面积（EpCAM、CK和AFP）的联合生物标志物表达表现良好，曲线下面积为0.92，在检测早期和AFP阴性的HCC以及AFP阴性的LC病例中具有高灵敏度和特异性。
CTC的计数和细胞面积可用作早期检测HCC和指导治疗的生物标志物。
