FAM172A expression in circulating tumor cells for prediction of high-risk subgroups of colorectal cancer

Abstract

Objectives: Previous studies used enumerated circulating tumor cells (CTCs) to predict prognosis and therapeutic effect in several types of cancers. However, increasing evidence showed that only enumerated CTCs were not enough to reflect the heterogeneity of tumors. Therefore, we classified different metastasis potentials of CTCs from colorectal cancer (CRC) patients to improve the accuracy of prognosis by CTCs. Methods: Blood samples were collected from 45 primary CRC patients. CTCs were enriched by blood filtration, and the RNA in situ hybridization method was used to identify and discriminate subgroups of CTCs. Later, FAM172A expression in individual CTCs was measured. Results: Three CTC subgroups (epithelial/biophenotypic/mesenchymal CTCs) were identified using epithelial–mesenchymal transition markers. In our research, mesenchymal CTCs significantly increased along with tumor progression, including developing distant metastasis and vascular invasion. Furthermore, FAM172A expression rate in mesenchymal CTCs was significantly higher than that in epithelial CTCs, which suggested that FAM172A may correlate with tumor malignancy. This hypothesis was further verified by FAM172A expression in mesenchymal CTCs strictly related to tumor aggressiveness factors. Finally, we revealed that mesenchymal CTCs and FAM172A expression may predict high-risk subgroups in stage II CRC. Conclusion: Our research proved that CTCs could serve as feasible surrogate samples to detect gene expression as a predictive biomarker for tumor evaluation.