Cui Chun-Hui, Chen Ri-Hong, Zhai Duan-Yang, Xie Lang, Qi Jia, Yu Jin-Long
Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Tumour Biol. 2017 Jun;39(6):1010428317699126. doi: 10.1177/1010428317699126.
Previous studies used to enumerate circulating tumor cells to predict prognosis and therapeutic effect of colorectal cancer. However, increasing studies have shown that only circulating tumor cells enumeration was not enough to reflect the heterogeneous condition of tumor. In this study, we classified different metastatic-potential circulating tumor cells from colorectal cancer patients and measured FAM172A expression in circulating tumor cells to improve accuracy of clinical diagnosis and treatment of colorectal cancer. Blood samples were collected from 45 primary colorectal cancer patients. Circulating tumor cells were enriched by blood filtration using isolation by size of epithelial tumor cells, and in situ hybridization with RNA method was used to identify and discriminate subgroups of circulating tumor cells. Afterwards, FAM172A expression in individual circulating tumor cells was measured. Three circulating tumor cell subgroups (epithelial/biophenotypic/mesenchymal circulating tumor cells) were identified using epithelial-mesenchymal transition markers. In our research, mesenchymal circulating tumor cells significantly increased along with tumor progression, development of distant metastasis, and vascular invasion. Furthermore, FAM172A expression rate in mesenchymal circulating tumor cells was significantly higher than that in epithelial circulating tumor cells, which suggested that FAM172A may correlate with malignant degree of tumor. This hypothesis was further verified by FAM172A expression in mesenchymal circulating tumor cells, which was strictly related to tumor aggressiveness factors. Mesenchymal circulating tumor cells and FAM172A detection may predict highrisk stage II colorectal cancer. Our research proved that circulating tumor cells were feasible surrogate samples to detect gene expression and could serve as a predictive biomarker for tumor evaluation.
以往的研究常通过对循环肿瘤细胞进行计数来预测结直肠癌的预后和治疗效果。然而，越来越多的研究表明，仅循环肿瘤细胞计数不足以反映肿瘤的异质性状况。在本研究中，我们对结直肠癌患者不同转移潜能的循环肿瘤细胞进行分类，并检测循环肿瘤细胞中FAM172A的表达，以提高结直肠癌临床诊断和治疗的准确性。收集了45例原发性结直肠癌患者的血样。采用上皮肿瘤细胞大小分离法通过血液过滤富集循环肿瘤细胞，并使用RNA原位杂交法识别和区分循环肿瘤细胞亚群。随后，检测单个循环肿瘤细胞中FAM172A的表达。使用上皮-间质转化标志物鉴定出三个循环肿瘤细胞亚群（上皮型/双表型/间质型循环肿瘤细胞）。在我们的研究中，间质型循环肿瘤细胞随着肿瘤进展以及远处转移和血管侵犯的发生而显著增加。此外，间质型循环肿瘤细胞中FAM172A的表达率显著高于上皮型循环肿瘤细胞，这表明FAM172A可能与肿瘤的恶性程度相关。这一假设通过间质型循环肿瘤细胞中FAM172A的表达得到进一步验证，其与肿瘤侵袭性因素密切相关。间质型循环肿瘤细胞和FAM172A检测可能预测高危II期结直肠癌。我们的研究证明，循环肿瘤细胞是检测基因表达的可行替代样本，可作为肿瘤评估的预测生物标志物。
