The rare circulating tumor microemboli as a biomarker contributes to predicting early colorectal cancer recurrences after medical treatment.

Early prognosis of cancer recurrence remains difficult partially due to insufficient and ineffective screening biomarkers or regimes. This study evaluated the rare circulating tumor microemboli (CTM) from liquid biopsy individually and together with circulating tumor cells (CTCs) and serum CEA/CA19-9 in a panel, on early prediction of colorectal cancer (CRC) recurrence. Stained CTCs/CTM were detected by a microfluidic chip-based automatic rare-cell imaging platform. ROC, AUC, Kaplan-Meier survival, and Cox proportional hazard models regarding 4 selected biomarkers were analyzed. The relative risk, odds ratio, predictive accuracy, and positive/negative predictive value of biomarkers individually and in combination, to predict CRC recurrence were assessed and preliminarily validated. The EpCAM+Hochest+CD45- CTCs/CTM could be found in all cancer stages, where more recurrences were observed in late-stage cases. Significant correlations between CTCs/CTM with metastatic stages and clinical treatment were illustrated. CA19-9 and CTM could be seen as independent risk factors in patient survivals, while stratified patients by grouped biomarkers on the Kaplan-Meier analyses presented more significant differences in predicting CRC recurrences. By monitoring the panel of selected biomarkers, disease progressions of 4 CRC patients during follow-up visits after first treatments within 3 years were predicted successfully. This study unveiled the value of rare CTM on clinical studies and a panel of selected biomarkers on predicting CRC recurrences in patients at the early time after medical treatment, in which the CTM and serum CA19-9 could be applied in clinical surveillance and CRC management to improve the accuracy.

Potential Values of Circulating microRNA-21 to Predict Early Recurrence in Patients with Colorectal Cancer after Treatments.

Insufficient prognosis of local recurrence contributes to the poor progression-free survival rate and death in colorectal cancer (CRC) patients. Various biomarkers have been explored in predicting CRC recurrence. This study investigated the expressions of plasma/exosomal microRNA-21 (miR-21) in 113 CRC patients by qPCR, their values of predicting CRC recurrence, and the possibility to improve the prognostic efficacy in early CRC recurrence in stratified patients by combined biomarkers including circulating miR-21s, circulating tumour cells/microemboli (CTCs/CTM), and serum carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9). Expressions of plasma and exosomal miR-21s were significantly correlated (p < 0.0001) in all and late-stage patients, presenting similar correlations with other biomarkers. However, stage IV patients stratified by a high level of exosomal miR-21 and stage I to III patients stratified by a high level of plasma miR-21 displayed significantly worse survival outcomes in predicting CRC recurrence, suggesting their different values to predict CRC recurrence in stratified patients. Comparable and even better performances in predicting CRC recurrence in late-stage patients were found by CTCs/CTM from our blood samples as sensitive biomarkers. Improved prognosing efficacy in CRC recurrence and better outcomes to significantly differentiate recurrence in stratified patients could be obtained by analysing combined biomarkers.