CD133+CD54+CD44+ circulating tumor cells as a biomarker of treatment selection and liver metastasis in patients with colorectal cancer

Abstract

IntroductionLiver is the most common site of distant metastasis in colorectal cancer (CRC). Early diagnosis and appropriate treatment selection decides overall prognosis of patients. However, current diagnostic measures were basically imaging but not functional. Circulating tumor cells (CTCs) known as hold the key to understand the biology of metastatic mechanism provide a novel and auxiliary diagnostic strategy for CRC with liver metastasis (CRC-LM).ResultsThe expression of CD133+ and CD133+CD54+CD44+ cellular subpopulations were higher in the peripheral blood of CRC-LM patients when compared with those without metastasis (P<0.001). Multivariate analysis proved the association between the expression of CD133+CD44+CD54+ cellular subpopulation and the existence of CRC-LM (P<0.001). The combination of abdominal CT/MRI, CEA and the CD133+CD44+CD54+ cellular subpopulation showed increased detection and discrimination rate for liver metastasis, with a sensitivity of 88.2% and a specificity of 92.4%. Meanwhile, it also show accurate predictive value for liver metastasis (OR=2.898, 95% C.I.1.374–6.110).Materials and MethodFlow cytometry and multivariate analysis was performed to detect the expression of cancer initiating cells the correlation between cellular subpopulations and liver metastasis in patients with CRC. The receiver operating characteristic curves combined with the area under the curve were generated to compare the predictive ability of the cellular subpopulation for liver metastasis with current CT and MRI images.ConclusionsThe identification, expression and application of CTC subpopulations will provide an ideal cellular predictive marker for CRC liver metastasis and a potential marker for further investigation.

Prognostic value of CD133+CD54+CD44+ circulating tumor cells in colorectal cancer with liver metastasis

“…It was further showed that CD133 + CD44 + CD54 + subpopulation of CTCs was an independent prognostic factor for CRC patients with liver metastasis (HR = 6.459; 95% CI = 1.461–28.558; P = 0.014). In our previous research, we had reported that CD133 + CD44 + CD54 + subpopulation of CTCs in the peripheral blood was associated with liver metastasis and could be used as an auxiliary diagnostic marker for liver metastasis among CRC patients . This is the first study that reports CD133 + CD44 + CD54 + subpopulation of CTCs has a prognostic value in CRC patients with liver metastases, especially those who did not receive surgical treatment for metastases ( P < 0.001).…”

“…Peripheral blood samples were obtained from CRC patients attending our department and an informed consent was obtained from all the individuals. Peripheral blood samples were collected and prepared as per the protocol described in our previous report . In detail, CTCs from cell suspensions were characterized by multiparameter flow cytometry.…”

“…DAPI was used to identify and sort the dead cells. The remaining steps were the same as the protocol described in our previous report . The absolute CTCs or antibody‐positive cell numbers were derived from the absolute number of white blood cells provided by the hematological analyzer, and the percentage of CTCs or antibody‐positive cells was determined by flow cytometry, using the following formula: percentage of cells × white blood cells count/100.…”

“…We also had found that CD133 + cellular subpopulation could be used as a baseline to select and isolate CTCs in the peripheral blood of CRC patients using fluorescence‐activated cell sorting (FACS). We then reported that the expression of CD133 + CD54 + CD44 + cellular subpopulation of CTCs was significantly associated with liver metastasis in CRC patients . In this study, we aimed to explore whether this cellular subpopulation in the peripheral blood has a prognostic value for CRC patients, especially those with liver metastasis.…”

eTumorType, An Algorithm of Discriminating Cancer Types for Circulating Tumor Cells or Cell-Free DNAs in Blood

“…However, eTumorType is capable of discriminating cancer types, which is beyond the current studies on CTC or cfDNA data, as the majority of these studies only focused on finding features ( e.g. , CNV, mutation, microRNA, methylation, and gene expression) associated with specific cancer types [25], [26], [27], [28], [29], [30]. To our best knowledge, no such algorithms have been developed so far.…”