Abstract
BackgroundThis study explored the diagnostic power of preoperative circulating tumor cells (CTCs) for the presence of microvascular invasion (MVI) and the relationship between dynamic changes in postoperative CTCs and prognosis.MethodsA total of 137 patients were recruited for the study. Preoperative blood samples were collected from all patients to detect CTCs. The time points for blood collection were before the operation, during the operation, and at 1 week, 1 month, 2 months, 3 months, 6 months, and 1 year after surgery. The predictive power of CTC count for the presence of MVI was analyzed by receiver operating characteristic (ROC) curve analysis. According to recurrence status, 137 patients were divided into three groups: no recurrence, early recurrence, and non-early recurrence groups.ResultsA threshold CTC count of 5 showed the most significant power for predicting the existence of MVI. In multivariate analysis, the parameters of preoperative CTC count, alpha-fetoprotein (AFP) and tumor diameter were independent predictors of MVI (P < 0.05). A CTC count greater than or equal to 5 had better predictive value than AFP > 400 μg/L and tumor diameter > 5 cm. The number of intraoperative CTCs in the three groups did not increase compared to that before surgery (P > 0.05). The number of CTCs in the nonrecurrence group and the non-early recurrence group decreased significantly 1 week after surgery compared with the intraoperative values (P < 0.001), although there was no significant difference in the early recurrence group (P = 0.95). Patients with mean CTC count ≥5 had significantly worse long-term outcomes than those with mean CTC count < 5 (P < 0.001).ConclusionThe preoperative CTC counts in the peripheral blood of patients with HCC are closely correlated with MVI. The intraoperative manipulation of the lesion by the surgeon does not increase the number of CTCs in peripheral blood. Surgical removal of the tumor decreases the number of CTCs. The persistence of CTCs at a high level (≥ 5) after surgery suggests a risk of early recurrence.Clinical trial registrationRegistration number is ChiCTR-OOC-16010183, date of registration is 2016-12-18.
Highlights
This study explored the diagnostic power of preoperative circulating tumor cells (CTCs) for the presence of microvascular invasion (MVI) and the relationship between dynamic changes in postoperative Circulating tumor cell (CTC) and prognosis
By comparing the receiver operating characteristic (ROC) curve features and areas under the ROC curves (AUCs), the results showed that compared with AFP, tumor diameter and CTC, the multiparameter combination had the most significant power for predicting the presence of MVI
Alanine transaminase (ALT) alanine transaminase, AFP alpha fetoprotein, Hepatitis B surface antigen (HBsAg) hepatitis B surface antigen, ICG R15 min (%) indocyanine green 15 min retention rate, portal vein tumor thrombus (PVTT) portal vein tumor thrombosis, BCLC Barcelona Clinic Liver Cancer staging system, CTC circulating tumor cell recurrent group decreased significantly 1 week after surgery compared with that in the intraoperative group (1.1 versus 3.1, P < 0.001; 1.2 versus 5.5, P < 0.001), there was no significant difference in the early recurrence group (7.6 versus 7.5, P = 0.950)
Summary
This study explored the diagnostic power of preoperative circulating tumor cells (CTCs) for the presence of microvascular invasion (MVI) and the relationship between dynamic changes in postoperative CTCs and prognosis. Studies have suggested that microvascular invasion (MVI) in HCC is one of the most significant risk factors for recurrence and metastasis following curative surgical resection [4]. One study reported that independent predictors of MVI included tumor diameter > 2 cm, alpha-fetoprotein (AFP) > 200 ng/mL and PIVKA-II > 40 mAU/mL [7]. Previous research has reported that the incidence of MVI ranged from 15 to 57% in HCC specimens and was associated with tumor size, AFP and typical imaging features [8]. The application of predictors of MVI is still very limited when selecting therapeutic strategies and predicting prognosis [10]
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