Enhancing Prediction Performance by Add-On Combining Circulating Tumor Cell Count, CD45neg EpCAMneg Cell Count on Colorectal Cancer, Advance, and Metastasis

Abstract

Conventional circulating tumor cell (CTC) enumeration could ignore the CTCs more relevant to cancer metastasis. Thus, negative selection CTC enumeration was proposed, by which information on two cellular biomarkers (numbers of CTCs and CD45neg EpCAMneg cells) can be obtained. By combining this approach with the conventional biomarker carcinoembryonic antigen (CEA), this study aimed to explore whether any combination of these biomarkers could improve the predictive performance for colorectal cancer (CRC) or its status. In this work, these two cell populations in healthy donors and CRC patients were quantified. Results revealed that enumeration of these two cell populations was able to discriminate healthy donors from CRC patients, even patients with non-advanced CRC. Moreover, the combination of the two cell populations showed improved performance (AUROC: 0.893) for CRC prediction over the use of only one population. Compared with CEA alone, the combination of the three biomarkers increased the performance (AUROC) for advanced CRC prediction from 0.643 to 0.727. Compared with that of CEA alone for metastatic CRC prediction, the AUROC was increased from 0.780 to 0.837 when the CTC count was included. Overall, this study demonstrated that the combination of these two cellular biomarkers with CEA improved the predictive performance for CRC and its status.

Enhanced prognostic value of combined circulating tumor cells and serum carcinoembryonic antigen in patients with colorectal cancer

“…A recent study revealed the diagnostic value of CTC enumerations and found that improved accuracies of AUC in predicting metastatic CRC samples were obtained by analyzing the combination of CEA and CTCs, rather than by CEA alone. 56 A strong association existed between patients with CTCs and cancer stage as well as the individual T, N, and M staging. High CEA levels are also correlated in patients with five or more CTCs.…”

“…A recent study revealed the diagnostic value of CTC enumerations and found that improved accuracies of AUC in predicting metastatic CRC samples were obtained by analyzing the combination of CEA and CTCs, rather than by CEA alone. 56…”

Clinical Utility of Circulating Tumor Cells for Predicting Major Histopathological Response after Neoadjuvant Chemoradiotherapy in Patients with Esophageal Cancer

“…Nevertheless, CTCs might undergo an epithelial-tomesenchymal transition in metastatic disease after which their EpCAM expression is downregulated. These EpCAM − CTCs are considered as "atypical CTCs" and can also be analyzed using our protocol [25,26]. However, given the uncertain clinical significance of EpCAM − CTCs in patients with esophageal cancer, we only defined CTCs as Hoechst + CD45 − EpCAM + cells in this study.…”

Biological factors driving colorectal cancer metastasis

“…Clearly, only a small portion of CTCs can undergo metastasis, while multiple mechanisms in heterogeneous CTCs facilitate their metastatic potential by driving CTC interactions with immune and stromal cells[ 62 ]. First, Chiu et al [ 63 ] showed that, compared with carcinoembryonic antigen (CEA) alone, CTC detection increases the power of the area under the receiver operating characteristic curve for predicting mCRC (0.7800 vs 0.8378). Surprisingly, Le et al [ 64 ] showed that CTCs were not associated with the size or number of metastases, as determined after previously administered drug therapy, or disease-free survival (DFS).…”