Clonorchis sinensis on the prognosis of patients with spontaneous rupture of Hepatocellular Carcinoma: An inverse probability of treatment weighting analysis.

BACKGROUND: We examined the impact of the Clonorchis sinensis (C. sinensis) infection on the survival outcomes of spontaneous rupture Hepatocellular Carcinoma (srHCC) patients undergoing hepatectomy. METHODS: Between May 2013 and December 2021, 157 consecutive srHCC patients who underwent hepatectomy were divided into an no C. sinensis group (n = 126) and C. sinensis group (n = 31). To adjust for differences in preoperative characteristics an inverse probability of treatment weighting (IPTW) analysis was done, using propensity scores. Overall survival (OS) and recurrence-free survival (RFS) were compared before and after IPTW. Multivariate Cox regression analysis was performed to determine whether the C. sinensis infection was an independent prognostic factor after IPTW. RESULTS: In original cohort, the no C. sinensis group did not show a survival advantage over the C. sinensis group. After IPTW adjustment, the median OS for the C. sinensis group was 9 months, compared to 29 months for the no C. sinensis group. C. sinensis group have worse OS than no C. sinensis group (p = 0.024), while it did not differ in RFS(p = 0.065). The multivariate Cox regression analysis showed that C. sinensis infection and lower age were associated with worse OS. CONCLUSIONS: The C. sinensis infection has an adverse impact on os in srHCC patients who underwent hepatectomy.

Integrating single-cell and bulk RNA sequencing reveals CK19 + cancer stem cells and their specific SPP1 + tumor-associated macrophage niche in HBV-related hepatocellular carcinoma.

PURPOSE: Cytokeratin 19-positive cancer stem cells (CK19 + CSCs) and their tumor-associated macrophages (TAMs) have not been fully explored yet in the hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: Single-cell RNA sequencing was performed on the viable cells obtained from 11 treatment-naïve HBV-associated HCC patients, including 8 CK19 + patients, to elucidate their transcriptomic landscape, CK19 + CSC heterogeneity, and immune microenvironment. Two in-house primary HCC cohorts (96 cases-related HBV and 89 cases with recurrence), TCGA external cohort, and in vitro and in vivo experiments were used to validate the results. RESULTS: A total of 64,581 single cells derived from the human HCC and adjacent normal tissues were sequenced, and 11 cell types were identified. The result showed that CK19 + CSCs were phenotypically and transcriptionally heterogeneous, co-expressed multiple hepatics CSC markers, and were positively correlated with worse prognosis. Moreover, the SPP1 + TAMs (TAM_SPP1) with strong M2-like features and worse prognosis were specifically enriched in the CK19 + HCC and promoted tumor invasion and metastasis by activating angiogenesis. Importantly, matrix metalloproteinase 9 (MMP9) derived from TAM_SPP1, as the hub gene of CK19 + HCC, was activated by the VEGFA signal. CONCLUSIONS: This study revealed the heterogeneity and stemness characteristics of CK19 + CSCs and specific immunosuppressive TAM_SPP1 in CK19 + HCC. The VEGFA signal can activate TAM_SPP1-derived MMP9 to promote the invasion and metastasis of CK19 + HCC tumors. This might provide novel insights into the clinical treatment of HCC patients.

High Platelet Count is a Potential Prognostic Factor of the Early Recurrence of Hepatocellular Carcinoma in the Presence of Circulating Tumor Cells.

Purpose: Recent studies indicated the vital role of platelet in enhancing the survival of circulating tumor cells (CTCs) in the blood, thereby stimulating the metastasis of tumors. CTCs have been considered an indicator of early tumor recurrence. Therefore, this study evaluated the prognostic potential of platelet count in predicting the early recurrence of hepatocellular carcinoma (HCC) in the presence of CTCs. Patients and Methods: 127 patients, whose preoperative CTCs were detected, were enrolled in this study. Univariate analysis was performed to identify the significant association of factors with the early recurrence of HCC, followed by multivariate analysis to determine the independent prognostic indicators. The prediction potential was evaluated using receiver operating characteristic (ROC) curves. Results: A total of 81 (63.7%) patients showed early HCC recurrence. The platelet count ≥225×109/L (hazard ratio, HR: 1.679, P = 0.041), CTCs >5/5 mL (HR: 2.467, P = 0.001), and presence of microvascular invasion (MVI) (HR: 2.580, P = 0.002) were independent factors correlated with the early recurrence of HCC in multivariate analysis. The prognostic potential of the combined CTCs-platelet count (0.738) was better than that of CTCs (0.703) and platelet (0.604) alone. The subgroup analysis, excluding 23 patients with pathological cirrhosis and splenomegaly, showed that the platelet count ≥225×109/L and CTCs >5/5 mL were also independent factors of early HCC recurrence. The prediction potential of the combined CTCs-platelet count was 0.753, which was better than that of the whole cohort. Kaplan-Meier survival curve analysis indicated that the HCC patients with high platelet or CTCs had the worse recurrence-free survival (RFS). Conclusion: The high platelet count was an independent factor of early HCC recurrence in the presence of CTCs. The combination of preoperative CTCs and platelet count could effectively predict the early recurrence of HCC. The subgroup analysis also showed similar results.

Combination of Preoperative Circulating Tumor Cell Count and Neutrophil-Lymphocyte Ratio for Prognostic Prediction in Hepatocellular Carcinoma Patients after Curative Hepatectomy.

Background: Both the preoperative neutrophil-lymphocyte ratio (NLR) and circulating tumor cell count (CTC) are associated with poor prognosis in hepatocellular carcinoma (HCC). The purpose of this study was to explore the prognostic value of these two indices (CTC-NLR) in HCC. Methods: We retrospectively collected demographic and clinical data, including NLR and CTC, from 97 patients with HCC who underwent curative hepatectomy at our institution from March 2014 to May 2017. X-Tile software was used to confirm the optimal cut-off value of NLR and CTC for predicting overall survival (OS) in this study. OS were also analyzed using Kaplan-Meier and Cox regression methods. Based on preoperative CTC and NLR, patients were divided into three groups: CTC-NLR (0), CTC-NLR (1), and CTC-NLR (2). Relationships of CTC-NLR with clinicopathological factors and survival were evaluated. Results: Preoperatively, CTC positively correlated with NLR. Patients with NLR and CTC higher than the cut-offs had shorter OS than patients with low NLR and CTC. Kaplan-Meier analysis, and log-rank tests revealed significantly lower OS among patients with CTC-NLR scores of 0, 1, and 2. Uni- and multivariate analyses showed that CTC-NLR (hazard ratio 2.050, P = 0.005), CTC (hazard ratio 2.285, P = 0.032), and NLR (hazard ratio 1.902, P = 0.048) were independent predictor of OS. A time-dependent ROC curve indicated that the prognostic efficacy of the CTC-NLR at 1 year (0.714) was better than that of NLR (0.687) and CTC (0.590); the prognostic efficacy of the CTC-NLR at 2 years (0.746) was better than that of NLR (0.711) and CTC (0.601); the prognostic efficacy of the CTC-NLR at 3 years (0.742) was better than that of NLR (0.694) and CTC (0.629). Conclusions: HCC patients with higher NLR and CTC tend to show shorter OS. Preoperative CTC-NLR may be associated with poor survival and might be a reliable prognostic predictor in HCC after curative hepatectomy.

Combining Pre- and Postoperative Lymphocyte-C-Reactive Protein Ratios Can Better Predict Hepatocellular Carcinoma Prognosis After Partial Hepatectomy.

Background: Various preoperative inflammatory indicators have been identified as potential predictors of poor prognosis in patients with hepatocellular carcinoma (HCC), but the role of postoperative inflammatory indicators remains unclear. This study aimed to explore the prognostic value of the postoperative lymphocyte-C-reactive protein ratio (PostLCR) on its own and combined with preoperative LCR (PreLCR). Methods: A total of 290 patients with primary HCC were retrospectively enrolled in the study. Univariate analysis was used to identify factors significantly associated with poor disease-free survival (DFS) and overall survival (OS), then multivariate analysis was performed to identify independent prognostic indicators of poor survival. Prognostic models based on preoperative, postoperative, and both types of indicators were then constructed, and their predictive performance were evaluated using time-dependent receiver operating characteristic curves and the concordance index (C-index). Results: PreLCR and PostLCR levels correlated with DFS and OS more strongly than other pre- and postoperative inflammatory indicators, respectively. Decreased PreLCR and PostLCR were independent prognostic factors for both DFS and OS, while HCC patients with decreased PreLCR and PostLCR had worse prognosis than patients with increased PreLCR and PostLCR. Patients into three groups based on their cut-off values of PreLCR and PostLCR, Kaplan-Meier survival analysis indicated that HCC patients with low PreLCR and PostLCR had the worst DFS and OS. The combined model showed better predictive performance at 1 and 3 years post-surgery than individual pre- and postoperative models, the American Joint Committee on Cancer/Tumor-Node-Metastasis (8th edition) staging system and the Barcelona Clinic Liver Cancer system. The combine model demonstrated a markedly superior C-index compared with the other models in DFS and OS. Conclusion: Our study showed PreLCR and PostLCR are independent predictors of DFS and OS in HCC patients after partial hepatectomy. Models that include both PreLCR and PostLCR can predict prognosis better than well-established clinical staging systems.