PURPOSE: The role of circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is not fully understood.; METHODS: In this retrospective analysis, we included 316 HCC patients who underwent hepatectomy and preoperative CTC detection. We selected 41 pairs of matched HCC patients with and without PVTT using propensity score matching (PSM) analysis. We compared the preoperative CTC counts in patients from both the full cohort and the PSM model. We also analyzed their associations with disease-free survival (DFS) and overall survival (OS).; RESULTS: Before and after PSM analysis, the preoperative CTC counts in the HCC with PVTT group were substantially higher than in the HCC without PVTT group. In both the full cohort of patients and the PSM model, patients with CTC≥2 had significantly shorter OS and DFS than patients with CTC<2. The outcomes of HCC patients with PVTT could be well differentiated by preoperative CTC levels. HCC patients with CTC≥2 had noticeably shorter OS (9.9months vs. 24.6months, P=0.0003) and DFS (6.0months vs. 12.3months, P=0.0041) than those with CTC<2. Moreover, preoperative CTC≥2 remained an independent predictor in all groups' multivariate analysis.; CONCLUSION: We discovered a link between preoperative CTC counts and the occurrence of PVTT and confirmed the prognostic significance of preoperative CTC in HCC patients with PVTT. These findings suggest that preoperative CTC counts have the potential to assist in identifying patients with HCC and PVTT who may benefit from surgery. © 2023. The Author(s).

BACKGROUNDThe long-term effect of anatomic resection (AR) is better than that of nonanatomic resection (NAR). At present, there is no study on microvascular invasion (MVI) and liver resection types.AIMTo explore whether AR improves long-term survival in patients with hepatocellular carcinoma (HCC) by removing the peritumoral MVI.METHODSA total of 217 patients diagnosed with HCC were enrolled in the study. The surgical margin was routinely measured. According to the stratification of different tumor diameters, patients were divided into the following groups: <= 2 cm group, 2-5 cm group, and > 5 cm group.RESULTSIn the 2-5 cm diameter group, the overall survival (OS) of MVI positive patients was significantly better than that of MVI negative patients (P = 0.031). For the MVI positive patients, there was a statistically significant difference between AR and NAR (P = 0.027). AR leads to a wider surgical margin than NAR (2.0 +/- 2.3 cm vs 0.7 +/- 0.5 cm, P < 0.001). In the groups with tumor diameters < 2 cm, both AR and NAR can obtain a wide surgical margin, and the surgical margins of AR are wider than that of NAR (3.5 +/- 5.8 cm vs 1.6 +/- 0.5 cm, P = 0.048). In the groups with tumor diameters > 5 cm, both AR and NAR fail to obtain wide surgical margin (0.6 +/- 1.0 cm vs 0.7 +/- 0.4 cm, P = 0.491).CONCLUSIONFor patients with a tumor diameter of 2-5 cm, AR can achieve the removal of peritumoral MVI by obtaining a wide incision margin, reduce postoperative recurrence, and improve prognosis.

Background: Growing evidence suggests that circulating tumor cell (CTC) clusters may be an important factor in the metastatic process, but their role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to characterize the molecular and clinical features of CTC cluster-positive human HCC and to assess its prognostic value in HCC patients.Methods: The CTCs and CTC clusters were evaluated in 204 HCC patients using CellSearch(TM) System. The counts of CTCs and CTC clusters were correlated with different clinical features, while their associations with progression-free survival (PFS) and overall survival (OS) were evaluated integrally and hierarchically by Kaplan-Meier estimates or Cox proportional regression analysis. Five cases each of CTC cluster-negative and cluster-positive patients were selected for RNA-sequencing analysis. The results of gene enrichment analysis were further verified using tissue microarray (TMA) by immunohistochemistry (IHC).Results: CTCs and CTC clusters were detected in 76 (37.3%) and 19 (9.3%) of 204 preoperative samples, respectively. CTC cluster-positive HCC represented an aggressive HCC phenotype with larger tumor size, more frequent microvascular invasion, and higher tumor stages. The survival of HCC patients utilizing CTCs and CTC clusters individually showed prognostic significance, while joint analysis revealed patients in Group III (CTC >= 2 and CTC cluster > 0) had the worst outcome. Stratified analysis of outcomes in Barcelona Clinic Liver Cancer (BCLC) and tumor-node-metastasis (TNM) stages indicated that patients with CTC clusters had significantly poorer prognosis in each stage than those without CTC clusters. Moreover, the RNA sequencing and TMA staining results showed that CTC cluster-positive HCCs were usually associated with Wnt/beta-catenin signaling activation.Conclusion: The presence of CTC clusters characterizes an aggressive HCC subtype. CTC clusters may be used as a biomarker in predicting the prognosis on each stage of malignancy in HCC, which provides evidence for formulating therapeutic strategies for more precise treatment.

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 mu g/L and tumor diameter>5cm. 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.

In recent years, an increasing number of circular RNAs (circRNAs) have been discovered in hepatocellular carcinoma (HCC). However, the functions of most circRNAs require further investigation. Here, we found that circBACH1 was significantly upregulated in HCC tissues and that high circBACH1 levels were closely associated with poor prognosis. In addition, circBACH1 could promote HCC growth by accelerating cell cycle progression in vitro and in vivo. We next investigated the cellular and molecular mechanisms and discovered that circBACH1 inhibited p27 translation, which influenced cell cycle progression. Moreover, we revealed that circBACH1 could combine directly with HuR using RNA immunoprecipitation assays, pull-down assays, and electrophoretic mobility shift assays. The combination of these molecules facilitated HuR translocation from the nucleus to the cytoplasm according to the fluorescence in situ hybridization and immunofluorescence results. Finally, silencing HuR abrogated circBACH1's inhibition of p27 translation and abolished the circBACH1-induced effect on HCC proliferation. In sum, circBACH1 plays a significant role as an oncogene through the circBACH1/HuR/p27 axis in HCC development.

Hepatocellular carcinoma (HCC) is a highly malignant disease with a poor prognosis and high mortality due to a low early diagnosis rate, resistance to systemic treatments and progression to late-stage liver disease. Owing to limitations in the detection of HCC and the lack of awareness of healthcare systems, fewer than 40% of HCC patients are eligible for surgery due to advanced stages of the disease at the time of diagnosis and the occurrence of multiple lesions in the cirrhotic or fibrotic liver. At present, the updated American Association for the Study of Liver Disease (AASLD) guidelines no longer recommend alpha-fetoprotein (AFP) testing as a part of diagnostic evaluation. Thus, it is imperative to establish a novel diagnostic strategy with high sensitivity and reliability to monitor risk factors to detect HCC at an early stage. In recent years, "liquid biopsy," (including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)), has emerged as a technique for the characterization of circulating cells, providing a strong basis for the individualized treatment of patients. As a noninvasive detection method, liquid biopsy is expected to play an important role in the early diagnosis, dynamic monitoring of cancer patients and drug screening. In this review, we will focus on the clinical applications, recent studies and future prospects of liquid biopsy, particularly focusing on HCC.

BACKGROUND: This study explored the effect of liver resection on perioperative circulating tumor cells (CTCs) and found that the prognostic significance of surgery was associated with changes in CTC counts in patients with hepatocellular carcinoma (HCC).; METHODS: One hundred thirty-nine patients with HCC were consecutively enrolled. The time-points for collecting blood were one day before operation and three days after operation. CTCs in the peripheral blood were detected by the CellSearch System.; RESULTS: Both CTC detection incidence and mean CTC counts showed greater increases postoperatively (54%, mean 1.54 cells) than preoperatively (43%, mean 1.13 cells). The postoperative CTC counts increased in 41.7% of patients, decreased in 25.2% of patients and did not change in 33.1% of patients. The increase in postoperative CTC counts was significantly associated with the macroscopic tumor thrombus status. Patients with increased postoperative CTC counts (from preoperative CTC<2 to postoperative CTC≥2) had significantly shorter disease-free survival (DFS) and overall survival (OS) than did patients with persistent CTC<2. Patients with persistent CTC levels of ≥2 had the worst prognoses.; CONCLUSIONS: Surgical liver resection is associated with an increase in CTC counts, and increased postoperative CTC numbers are associated with a worse prognosis in patients with HCC.