Ningling Ge

Prognostic significance of the neutrophil-to-lymphocyte ratio in primary liver cancer: a meta-analysis.

The neutrophil-to-lymphocyte ratio (NLR) is a useful biomarker that reflects systemic inflammation responses. However, the prognostic value of the NLR in patients with primary liver cancer (PLC) remains controversial. We performed a meta-analysis of 26 studies (comprising 4,461 patients) to evaluate the association between the pre-treatment NLR and clinical outcomes of overall survival (OS) and disease-free survival (DFS) in patients with PLC. The correlation between NLR and tumor characteristics or other inflammation-related parameters was also assessed. Data were synthesized using the random-effects model of DerSimonian and Laird, and the hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was used to estimate effect size. Our analysis indicated that a high NLR predicted poor OS (HR, 2.102; 95% CI: 1.741–2.538) and DFS (HR, 2.474; 95% CI: 1.855–3.300) for PLC. A high NLR was associated with the presence of tumor vascular invasion (OR: 1.889, 95% CI: 1.487–2.400; p<0.001) and an elevated alpha-fetoprotein level (OR: 1.536; 95% CI: 1.152–2.048; p = 0.003). Thus, we conclude that a high NLR indicates a poor prognosis for patients with PLC and may also be predictive for PLC invasion and metastasis. Subgroup analysis suggested that the predictive role of NLR in cholangiocarcinoma is limited, and a further large study to confirm these findings is warranted.

Caveolin-1 Confers Resistance of Hepatoma Cells to Anoikis by Activating IGF-1 Pathway.

Background/Aims: Anoikis resistance is a prerequisite for hepatocellular carcinoma (HCC) metastasis. The role of Caveolin-1 (CAV1) in anoikis resistance of HCC remains unclear. Methods: The oncogenic effect of CAV1 on anchor-independent growth and anoikis resistance was investigated by overexpression and knockdown of CAV1 in hepatoma cells. IGF-1 pathway and its downstream signals were detected by immunoblot analysis. Caveolae invagination and IGF-1R internalization was studied by electron microscopy and 125I-IGF1 internalization assay, respectively. The role of IGF-1R and tyrosine-14 residue (Y-14) of CAV1 was explored by deletion experiment and mutation experiment, respectively. The correlation of CAV1 and IGF-1R was further examined by immunochemical analysis in 120 HCC specimens. Results: CAV1 could promote anchor-independent growth and anoikis resistance in hepatoma cells. CAV1-overexpression increased the expression of IGF-1R and subsequently activated PI3K/Akt and RAF/MEK/ERK pathway, while CAV1 knockdown showed the opposite effect. The mechanism study revealed that CAV1 facilitated caveolae invagination and 125I-IGF1 internalization. IGF-1R deletion or Y-14 mutation reversed CAV1 mediated anchor-independent growth and anoikis resistance. In addition, CAV1 expression was positively related to IGF-1R expression in human HCC tissues. Conclusion: CAV1 confers resistance of hepatoma cells to anoikis by activating IGF-1 pathway, providing a potential therapeutic target for HCC metastasis.

Role of lamivudine with transarterial chemoembolization in the survival of patients with hepatocellular carcinoma

The purpose of the present study was to determine whether lamivudine in combination with transarterial chemoembolization (TACE) could reduce hepatitis B virus (HBV) activation and improve the survival of patients with hepatocellular carcinoma (HCC).

High platelet counts increase metastatic risk in huge hepatocellular carcinoma undergoing transarterial chemoembolization.

Accumulating evidence suggests platelets play critical roles in tumor metastasis. Moreover, the role of platelets in metastasis is partially correlated with inflammation. However, evidence regarding the contribution of platelets to hepatocellular carcinoma (HCC) metastasis is lacking. This study investigated the association between platelets and metastatic risk in HCC.

Sex-Determination Gene SRY Potentially Associates with Poor Prognosis but Not Sex Bias in Hepatocellular Carcinoma

BackgroundGender disparity is well known in hepatocellular carcinoma (HCC). SRY is a critical sex-determination gene involved in embryonic development.AimThe potential relevance of SRY to HCC progression was evaluated.MethodsSRY expression in HCC cell lines and tissues was evaluated. Invasion and wound healing assays were used to evaluate the role of SRY in HCC cell migration. The prognostic value of SRY for HCC patient survival was evaluated.ResultsSRY was highly expressed in HCC cell lines and tumor tissues. Downregulation of SRY expression decreased migration and invasion potential of HCC cells. High SRY levels correlated with poor HCC patient survival. Additionally, neither spatial position nor expression intensity of SRY was correlated with HCC gender disparity.ConclusionsHigh levels of SRY expression correlated with cancer progression and poor HCC patient survival. However, high SRY levels are not significantly correlated with HCC sex bias.

Goosecoid Promotes the Metastasis of Hepatocellular Carcinoma by Modulating the Epithelial-Mesenchymal Transition

The homeobox gene, goosecoid (GSC), is a transcription factor that participates in cell migration during embryonic development. Because cell migration during development has characteristics similar to cell invasion during metastasis, we evaluated the potential role of GSC in the metastasis of hepatocellular carcinoma (HCC). GSC expression in HCC cell lines and tissues was evaluated, and its effects on the migration potential of HCC cells were determined by GSC knock-down and overexpression methods. In addition, the prognostic role of GSC expression in the metastasis of cancer cells in HCC patients was determined. Our data showed that GSC was highly expressed in several HCC cell lines, particularly in a highly metastatic HCC cell line. Overexpression of GSC promoted cell migration and invasion of HCC cells in vitro. Gain-of-function induced the epithelial-mesenchymal transition but not collective cell migration, whereas loss-of-function induced the reverse change. High-level expression of GSC correlated closely with poor survival and lung metastasis in HCC patients; lung metastases showed more upregulated GSC expression than the primary tumor. We conclude that GSC promotes metastasis of HCC potentially through initiating the epithelial-mesenchymal transition. GSC is also a prognostic factor for poor survival and metastasis of HCC, which suggests its potential as a therapeutic target for metastatic HCC.

Oxaliplatin and 5-fluorouracil hepatic infusion with lipiodolized chemoembolization in large hepatocellular carcinoma

AIM To investigate transarterial chemoembolization (TACE) with hepatic infusion of oxaliplatin and 5-fluorouracil and Lipiodol chemoembolization in large hepatocellular carcinoma (HCC). METHODS In this retrospective study, 132 patients with unresectable HCCs larger than 10 cm were treated with hepatic infusion of oxaliplatin and 5-fluorouracil followed by Lipiodol chemoembolization. The primary endpoint was overall survival (OS). Sixteen-week disease-control rate, time to progression (TTP), and major complications were also studied. Univariate and multivariate analyses were performed to identify prognostic factors affecting OS and TTP. RESULTS A total of 319 procedures were performed in the 132 patients. Eleven (8.3%) patients received radical resection following TACE treatment (median time to initial TACE 4.3 ± 2.3 mo). The median OS and TTP were 10.3 and 3.0 mo respectively, with a 50.0% 16-wk disease-control rate. Major complications were encountered in 6.0% (8/132) of patients following TACE and included serious jaundice in 1.5% (2/132) patients, aleukia in 1.5% (2/132), and hepatic failure in 3.0% (4/132). One patient died within one month due to serious hepatic failure and severe sepsis after receiving the second TACE. The risk factor associated with TTP was baseline alpha-fetoprotein level, and vascular invasion was an independent factor related to OS. CONCLUSION Hepatic infusion of oxaliplatin and 5-fluorouracil followed by lipiodolized-chemoembolization is a safe and promising treatment for patients with HCCs larger than 10 cm in diameter.

Hepatitis B surface antigen predicts recurrence after radiofrequency ablation in patients with low hepatitis B virus loads

Abstract Radiofrequency ablation (RFA) is a first-line option for the treatment of small liver cancers, but the recurrence remains a problem affecting long-term survival. Hepatitis B virus (HBV) activity is associated with the prognosis of hepatocellular carcinoma (HCC). We investigated the significance of hepatitis B surface antigen (HBsAg) in HCC recurrence after curative RFA treatment in HBV-related small HCC. We enrolled 404 HBV-related patients with small HCC (⩽3 cm) who underwent curative RFA. We used univariate and multivariate analyses to investigate the baseline levels of HBsAg, in addition to other known risk factors for HCC recurrence, for association with HCC tumor recurrence after curative RFA. The overall 1-, 2-, and 3-year recurrence-free survival (RFS) rates were 75%, 50%, and 34%, respectively. The median recurrence-free time was 25 months. The level of HBsAg was an independent risk factor for recurrence in patients with lower HBV-DNA levels. In hepatitis Be antigen (HBeAg)-negative patients, the 1-, 2-, and 3-year RFS rates were 79%, 64%, and 44%, respectively, for that with low HBsAg levels, compared with 73%, 50%, and 37%, respectively, for that with high HBsAg levels (P = .039). HBsAg might serve as a valuable marker to evaluate the risk of HCC recurrence in HBeAg-negative patients with low HBV viral load.