Preoperative platelet-to-lymphocyte ratio is a valuable prognostic biomarker in patients with hepatocellular carcinoma undergoing curative liver resection.

The Platelet to lymphocyte ratio (PLR) has been reported to predict prognosis of patients with hepatocellular carcinoma (HCC). This study examined the prognostic potential of stratified PLR for HCC patients undergoing curative liver resection. Medical records were retrospectively analyzed for 778 HCC patients undergoing curative liver resection at the Affiliated Tumor Hospital of Guangxi Medical University and the First People's Hospital of Changde between April 2010 and October 2013. Patients were stratified based on quintile analysis of their preoperative PLR, and patients in different quintiles were analyzed for overall survival (OS) and disease-free survival (DFS) using Kaplan-Meier analysis. Independent predictors of death or recurrence were explored using multivariable Cox proportional hazard regression. Higher PLR quintiles were significantly associated with poorer overall survival (p < 0.001). Multivariate analysis showed PLR to be an independent risk factor for OS (p = 0.003). Patients in PLR quintile 5 had lower overall survival than in quintile 1 (hazard ratio (HR) = 2.780, 95% confidence interval (CI): 1.769-4.367, p < 0.001). Although patients in PLR quintile 5 had significantly lower disease-free survival (DFS) than in quintile 1 (HR = 1.534, 95% CI: 1.112-2.117, p = 0.009), this association was not significant after multivariable adjustment (p = 0.220). Subgroup analysis also showed that PLR quintiles were significantly associated with poor OS in patients positive for HBsAg or with cirrhosis (both p < 0.001). Similar results were obtained when PLR was analyzed as a dichotomous variable with cut-off values of 110 and 115. Elevated preoperative PLR may be independently associated with poor OS and DFS in HCC patients following curative resection.

Stratified aspartate aminotransferase-to-platelet ratio index accurately predicts survival in hepatocellular carcinoma patients undergoing curative liver resection.

The aspartate aminotransferase-to-platelet ratio index has been reported to predict prognosis of patients with hepatocellular carcinoma. This study examined the prognostic potential of stratified aspartate aminotransferase-to-platelet ratio index for hepatocellular carcinoma patients undergoing curative liver resection. A total of 661 hepatocellular carcinoma patients were retrieved and the associations between aspartate aminotransferase-to-platelet ratio index and clinicopathological variables and survivals (overall survival and disease-free survival) were analyzed. Higher aspartate aminotransferase-to-platelet ratio index quartiles were significantly associated with poorer overall survival (p = 0.002) and disease-free survival (p = 0.001). Multivariate analysis showed aspartate aminotransferase-to-platelet ratio index to be an independent risk factor for overall survival (p = 0.018) and disease-free survival (p = 0.01). Patients in the highest aspartate aminotransferase-to-platelet ratio index quartile were at 44% greater risk of death than patients in the first quartile (hazard ratio = 1.445, 95% confidence interval = 1.081 - 1.931, p = 0.013), as well as 49% greater risk of recurrence (hazard ratio = 1.49, 95% confidence interval = 1.112-1.998, p = 0.008). Subgroup analysis also showed aspartate aminotransferase-to-platelet ratio index to be an independent predictor of poor overall survival and disease-free survival in patients positive for hepatitis B surface antigen or with cirrhosis (both p < 0.05). Similar results were obtained when aspartate aminotransferase-to-platelet ratio index was analyzed as a dichotomous variable with cutoff values of 0.25 and 0.62. Elevated preoperative aspartate aminotransferase-to-platelet ratio index may be independently associated with poor overall survival and disease-free survival in hepatocellular carcinoma patients following curative resection.

Systematic review comparing the safety and efficacy of conventional and drug-eluting bead transarterial chemoembolization for inoperable hepatocellular carcinoma.

AIM: Conventional transarterial chemoembolization (cTACE) is widely used for treating patients with inoperable hepatocellular carcinoma (HCC). A variation on the technique based on drug-eluting beads (DEB-TACE) has recently entered the clinic, but trials of its safety and efficacy have given conflicting results. This systematic review aimed to gain a current, comprehensive picture of how DEB-TACE compares with cTACE. METHODS: MEDLINE, EMBASE, the Cochrane Library, the Chinese National Knowledge Infrastructure database and clinical trial registries were searched through June 2014. Risk ratios (RR), hazard ratios (HR) and 95% confidence intervals (CI) were calculated. RESULTS: The analysis included four randomized controlled trials, one uncontrolled prospective study and one prospective case-control study, altogether involving 652 patients. Overall survival benefit was similar between cTACE and DEB-TACE patients (HR = 1.07, 95% CI = 0.82-1.40, P = 0.875). However, DEB-TACE was associated with a significantly higher objective tumor response rate (RR = 1.14, 95% CI = 1.01-1.29, P = 0.03) and a slightly lower incidence of adverse events. CONCLUSION: Though the available evidence suggests that although DEB-TACE is associated with better tumor response and potentially fewer adverse events, it does not provide greater survival benefit than cTACE. These results need to be validated in high-quality trials with large sample size.

Comparison of survival of patients with BCLC stage A hepatocellular carcinoma after hepatic resection or transarterial chemoembolization: a propensity score-based analysis.

BACKGROUND: It is unclear whether hepatic resection (HR) or transarterial chemoembolization (TACE) is associated with better outcomes for patients with hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage A. The present study compared survival for patients with BCLC stage A HCC treated by HR or TACE. METHODS: Our study examined 360 patients treated by HR and 221 treated by TACE. To reduce bias in patient selection, 152 pairs of propensity-score-matched patients were generated, and their long-term survival was compared using the Kaplan-Meier method. Independent predictors of survival were identified using the Cox proportional hazards model. RESULTS: Among propensity-score-matched pairs of patients with Child-Pugh A liver function who were treated by HR or TACE, the 1-, 3-, and 5-year overall survival rates were 75.5, 44.8, and 30.2 % after HR and 64.5, 24.1, and 13.7 % after TACE (P < 0.001). Serum AST level, serum AFP level, tumor size, and TACE independently predicted survival in Cox regression analysis. CONCLUSIONS: Our propensity-score-matched study confirmed that HR was associated with higher survival rates than was TACE in patients with BCLC stage A HCC.

Dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer.

Objectives: In this study, we compared the dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer. Furthermore, we investigated the potential impact of these changes on the occurrence of toxic side effects. Methods: Patients with gastric cancer who received adjuvant or first-line XELOX/SOX chemotherapy between January 2020 and June 2023 were enrolled. The Brief Conghua Scale was used to assess energy intake, and nutritional management was carried out with reference to the Chinese Guidelines for Nutritional Therapy of Cancer 2020. The NRS 2002 Nutritional Risk Screening Scale, PG-SGA scale, bioelectrical impedance analysis, and dynamic changes in lumbar 3 vertebral skeletal muscle index were compared between baseline and post-chemotherapy in the study. The neutropenia was evaluated using the Common Terminology Criteria for Adverse Events V.5.0, developed by the National Institutes of Health. Results: Dynamic follow-up was completed in 39 cases, with a mean follow-up time of 117.62 ± 43.38 days. The incidence of sarcopenia increased significantly after chemotherapy, escalating from 46.2% to 51.3%. After chemotherapy, the mean L3SMI decreased from 36.00 cm2/m2 to 34.99 cm2/m2. Furthermore, when compared to pre-chemotherapy values, the body composition indexes body mass index (BMI), SL3, fat mass free index (FFMI), lean body mass (LBM), and body surface area (BSA) were significantly reduced after chemotherapy. Regardless of baseline or post-chemotherapy status, the incidence of grade ≥ 3 neutropenia was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, when the skeletal muscle index decreased during chemotherapy, the incidence of grade ≥ 3 neutropenia was significantly higher in both the sarcopenia and non-sarcopenia groups compared to baseline. When the incidence of grade ≥ 3 neutropenia in the post-chemotherapy sarcopenia group was compared to baseline status, the increase was significantly higher in the sarcopenia group than in the maintenance/increase group. Conclusions: Skeletal muscle mass decreased progressively during XELOX/SOX chemotherapy in gastric cancer patients, followed by a higher incidence of grade ≥ 3 neutropenia.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Update Knowledge Assessment and Influencing Predictor of Female Fertility Preservation in Oncologists.

OBJECTIVE: This study aims to offer an update assessment of the knowledge of Chinese oncologists on female fertility preservation, and identify the determinants that influence the implementation of fertility preservation. METHODS: A total of 713 Chinese oncologists with different specialties completed the online self-report questionnaire to assess their understanding of fertility risks in cancer treatment, knowledge on female fertility preservation, and perceptions on the barriers in referring patients for fertility preservation. RESULTS: Although most oncologists were familiar with fertility risk in cancer treatment, half of them lacked the knowledge for reproduction and preservation methods. In the multivariable model, oncologists in a hospital with a specialized reproductive institution, positive precaution for fertility risk, and fertility preservation discussion with patients were significantly correlated with the possibility of fertility preservation referral. CONCLUSIONS: The intervention targets based on the update evaluation and identified influencing determinants will be helpful for all the oncofertility researchers, oncologists and institutions in future efforts for well-established female fertility preservation services.

Signature of prognostic epithelial-mesenchymal transition related long noncoding RNAs (ERLs) in hepatocellular carcinoma.

ABSTRACT: Reliable biomarkers are of great significance for the treatment and diagnosis of hepatocellular carcinoma (HCC). This study identified potential prognostic epithelial-mesenchymal transition related lncRNAs (ERLs) by the cancer genome atlas (TCGA) database and bioinformatics.The differential expression of long noncoding RNA (lncRNA) was obtained by analyzing the lncRNA data of 370 HCC samples in TCGA. Then, Pearson correlation analysis was carried out with EMT related genes (ERGs) from molecular signatures database. Combined with the univariate Cox expression analysis of the total survival rate of hepatocellular carcinoma (HCC) patients, the prognostic ERLs were obtained. Then use "step" function to select the optimal combination of constructing multivariate Cox expression model. The expression levels of ERLs in HCC samples were verified by real-time quantitative polymerase chain reaction.Finally, we identified 5 prognostic ERLs (AC023157.3, AC099850.3, AL031985.3, AL365203.2, CYTOR). The model showed that these prognostic markers were reliable independent predictors of risk factors (P value <.0001, hazard ratio [HR] = 2.400, 95% confidence interval [CI] = 1.667-3.454 for OS). In the time-dependent receiver operating characteristic analysis, this prognostic marker is a good predictor of HCC survival (area under the curve of 1 year, 2 years, 3 years, and 5 years are 0.754, 0.720, 0.704, and 0.662 respectively). We analyzed the correlation of clinical characteristics of these prognostic markers, and the results show that this prognostic marker is an independent factor that can predict the prognosis of HCC more accurately. In addition, by matching with the Molecular Signatures Database, we obtained 18 ERLs, and then constructed the HCC prognosis model and clinical feature correlation analysis using 5 prognostic ERLs. The results show that these prognostic markers have reliable independent predictive value. Bioinformatics analysis showed that these prognostic markers were involved in the regulation of EMT and related functions of tumor occurrence and migration.Five prognostic types of ERLs identified in this study can be used as potential biomarkers to predict the prognosis of HCC.

The lymphocyte-to-monocyte ratio is a superior predictor of overall survival compared to established biomarkers in HCC patients undergoing liver resection.

The aim of this study was to investigate the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in patients undergoing hepatectomy and to compare it to established biomarkers including the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Medical records were retrospectively analyzed for 652 HCC patients undergoing hepatectomy at the Affiliated Tumor Hospital of Guangxi Medical University and the First People's Hospital of Changde between April 2004 to April 2012. The correlation between the LMR and clinical variables were analyzed in Kaplan-Meier log-rank survival analysis and then multivariate Cox regression models trying to find relation with disease-free survival (DFS) and overall survival (OS). The area under the ROC curve (AUC) of the LMR(AUC:0.627) for predicting long-term survival was greater than that of the NLR(AUC:0.600) and the PLR(AUC:0.520).Multivariate analysis showed LMR to be an independent risk factor for OS (P = 0.002), and the NLR and PLR were not independently significant. Subgroup analysis also showed that LMR was significantly associated with poor DFS and OS in patients positive for HBsAg or with cirrhosis (both P < 0.001).Elevated preoperative LMR is an independently associated with poor OS and DFS in HCC patients following curative resection and appears to be superior to NLR and PLR.

Hepatic resection or transarterial chemoembolization for hepatocellular carcinoma within Milan criteria: A propensity score matching analysis.

This study aimed to compare the long-term survival of patients with hepatocellular carcinoma (HCC) within the Milan criteria who underwent hepatic resection (HR) or transarterial chemoembolization (TACE).Medical records were retrospectively analyzed for HCC patients within the Milan criteria treated at Affiliated Tumor Hospital of Guangxi Medical University between March 2003 and March 2008, 159 of whom underwent HR and 42 of whom underwent TACE. Long-term overall survival (OS) was evaluated using the Kaplan-Meier method before and after propensity score matching. Cox proportional hazard modeling was used to identify possible predictors of OS.Propensity score matching was used to generate 32 pairs of patients, for which OS was significantly higher after HR than TACE at 1 year, 96.6% versus 84.4%; 3 years, 75.4% versus 53.1%; 5 years, 48.8% versus 29.7%, respectively (P = .038). Among all patients with multinodular HCC (2-3 tumors ≤3 cm), HR was also associated with significantly higher OS than TACE at 1 year, 95.2% versus 72.7%; 3 years, 71.4% versus 9.1%; 5 years, 35.1% versus 0%, respectively (P < .001). By contrast, among all patients with a single HCC tumor ≤5 cm, HR and TACE were associated with similar OS at 1 year, 85.9% versus 90.3%; 3 years, 62.0% versus 61.3%; 5 years, 42.1% versus 33.2%, respectively (P = .332).HR provides survival benefit over TACE in HCC patients within the Milan criteria, especially patients with multinodular HCC involving 2 to 3 tumors ≤3 cm. However, HR and TACE appear to be similarly effective for patients with single-tumor HCC ≤5 cm.

Comparison of hepatectomy with or without hepatic inflow occlusion in patients with hepatocellular carcinoma: a single-center experience.

BACKGROUND: The negative effects of hepatic inflow occlusion (HIO) on postoperative liver function of patients with hepatocellular carcinoma (HCC) after liver resection have been reported. Nevertheless, whether or not HIO could influence the long-term outcomes remains unclear. METHODS: A total of 396 patients were included in this study and divided into without occlusion (WO) group (N.=112) and HIO group (N.=284). Aiming to minimize influence of selection bias and confounding variables, we used propensity score matching (PSM) of a 0.2 caliper to balance baseline variables. Overall survival (OS) and disease-free survival (DFS) were compared by the Kaplan-Meier method. Independent prognostic factors for OS and DFS were identified by Cox proportional hazards regression model. RESULTS: PSM were used to generate 101 pairs of patients. After PSM, OS was not significantly different between WO and HIO group (1-year: 86.1% vs. 83.2%; 3-year: 61.4% vs. 61.4%; 5-year: 45.5% vs. 39.6%; P = 0.626). Similar results of DFS were obtained between WO and HIO group (1-year: 54.5% vs. 53.5%; 3-year: 30.5% vs. 28.7%; 5-year: 14.2% vs. 14.9%; P=0.873). WO and HIO groups did not differ in 30-day, 90-day mortality and rate of postoperative complications (all P>0.05). CONCLUSIONS: Our data indicates that HIO might not negatively affect the OS and DFS of HCC patients undergoing liver resection and is likely to be a safe and viable option for intraoperative blood loss control.

Thymosin α1 therapy subsequent to radical hepatectomy in patients with hepatitis B virus-associated hepatocellular carcinoma: A retrospective controlled study.

The clinical efficacy of thymosin α1 (Tα1) therapy in patients with hepatocellular carcinoma (HCC) subsequent to radical hepatectomy is unclear. In the present study, the impact of Tα1 therapy on outcomes in HCC patients after radical hepatectomy was retrospectively evaluated. Medical records were retrospectively reviewed for 146 patients with hepatitis B virus (HBV)-associated HCC who were treated by radical hepatectomy and subsequently with Tα1 therapy, as well as for 412 control patients with HBV-associated HCC treated by radical hepatectomy. Propensity score matching was used to minimize confounding variables due to baseline differences. Liver function, recurrence-free survival and overall survival rates were compared between the two groups. Serum markers of liver function were significantly improved in the Tα1 group compared with the control group. The 1-, 2- and 3-year overall survival rates were 87.2, 82.0 and 68.4% in the Tα1 group and 78.2, 64.2 and 49.7% in the control group (P=0.011). The 1-, 2- and 3-year recurrence-free survival rates were 79.7, 70.8 and 67.3% in the Tα1 group and 69.9, 61.5 and 51.6% in the control group (P=0.019). The results suggested that post-hepatectomy Tα1 therapy improves liver function and significantly prolong recurrence-free and overall survival in patients with HBV-associated HCC.

Side population in hepatocellular carcinoma HCCLM3 cells is enriched with stem-like cancer cells.

Substantial evidence implicates that low-abundance cancer stem cells (CSCs) are responsible for tumor metastasis and recurrence in hepatocellular carcinoma (HCC). Side population (SP) cells possess typical CSCs-like features, and are frequently considered as a special subpopulation in which CSCs are enriched and in studies may be considered as a substitute for CSCs. The aim of the present study was to examine the abundance of SP cells in human HCC cell lines with different metastatic potentials and compare their CSC-like, tumorigenic and invasive properties with those of the main population (MP) cells. An experimental system is described for identifying SP cells and analyzing their CSC-like properties. The relative abundance of SP cells correlated directly with the metastatic potential of the HCC cell line: HCCLM3, 16.3±2.2%; MHCC97-H, 8.4±0.7%; MHCC97-L, 4.7±0.5%; and Huh7, 1.0±0.3% (P<0.05). SP cells isolated from HCCLM3 cultures showed significantly higher proliferation rates and clonogenicity than the corresponding MP cells, in addition to higher migration and invasive abilities in vitro and greater tumorigenicity in mice. Expression levels of all CSC-associated genes tested, except EpCAM and Oct4, were significantly higher in SP cells. The findings revealed that the proportion of SP cells correlates with metastatic potential, and SP cells demonstrated the characteristics expected of CSCs, implicating them in HCC metastasis. Further studies on the identification and characterization of SP cells using clinical HCC specimens will contribute to the understanding of how SP cells are involved in these disease processes.

Blood neutrophil-lymphocyte ratio predicts survival after hepatectomy for hepatocellular carcinoma: A propensity score-based analysis.

AIM: To investigate whether an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) can predict poor survival in patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed 526 patients with HCC who underwent surgery between 2004 and 2011. RESULTS: Preoperative NLR ≥ 2.81 was an independent predictor of poor disease-free survival (DFS, P < 0.001) and overall survival (OS, P = 0.044). Compared with patients who showed a preoperative NLR < 2.81 and postoperative increase, patients who showed preoperative NLR ≥ 2.81 and postoperative decrease had worse survival (DFS, P < 0.001; OS, P < 0.001). Among patients with preoperative NLR ≥ 2.81, survival was significantly higher among those showing a postoperative decrease in NLR than among those showing an increase (DFS, P < 0.001; OS, P < 0.001). When elevated, alpha-fetoprotein (AFP) provided no prognostic information, and so preoperative NLR ≥ 2.81 may be a good complementary indicator of poor OS whenever AFP levels are low or high. CONCLUSION: Preoperative NLR ≥ 2.81 may be an indicator of poor DFS and OS in patients with HCC undergoing surgery. Preoperative NLR ≥ 2.81 may be a good complementary indicator of poor OS when elevated AFP levels provide no prognostic information.

Cyclooxygenase-2 expression is associated with initiation of hepatocellular carcinoma, while prostaglandin receptor-1 expression predicts survival.

AIM: To determine whether cyclooxygenase-2 (COX-2) and prostaglandin E1 receptor (EP1) contribute to disease and whether they help predict prognosis. METHODS: We retrospectively reviewed the records of 116 patients with hepatocellular carcinoma (HCC) who underwent surgery between 2008 and 2011 at our hospital. Expression of COX-2 and EP1 receptor was examined by immunohistochemistry of formalin-fixed, paraffin-embedded tissues using polyclonal antibodies. Possible associations between immunohistochemical scores and survival were determined. RESULTS: Factors associated with poor overall survival (OS) were alpha-fetoprotein > 400 ng/mL, tumor size ≥ 5 cm, and high EP1 receptor expression, but not high COX-2 expression. Disease-free survival was not significantly different between patients with low or high levels of COX-2 or EP1. COX-2 immunoreactivity was significantly higher in well-differentiated HCC tissues (Edmondson grade I-II) than in poorly differentiated tissues (Edmondson grade III-IV) (P = 0.003). EP1 receptor immunoreactivity was significantly higher in poorly differentiated tissue than in well-differentiated tissue (P = 0.001). CONCLUSION: COX-2 expression appears to be linked to early HCC events (initiation), while EP1 receptor expression may participate in tumor progression and predict survival.

Obesity Does Not Influence Outcomes in Hepatocellular Carcinoma Patients following Curative Hepatectomy.

BACKGROUND: Whether obesity affects surgical outcomes in patients with hepatocellular carcinoma (HCC) is controversial. Here we retrospectively evaluated the impact of obesity on outcomes in HCC patients after curative hepatectomy. METHODS: Patients with Child-Pugh A liver function who underwent curative hepatectomy between 2006 and 2010 were categorized as obese (BMI ≥25 kg/m2, n = 68) and non-obese (<25 kg/m2, n = 242). To reduce interference from baseline differences between the two groups, propensity score-matched analysis was performed in the ratio 1:2 using a caliper width of 0.1. Surgical outcomes were compared for 61 obese and 115 non-obese patients. RESULTS: Obese patients had higher levels of albumin and aspartate aminotransferase, and more solitary tumors compared to the non-obese patients (all P<0.05). In the propensity-matched cohort, baseline characteristics did not differ between the two groups (all P>0.05). Obese and non-obese patients had comparable 30-day mortality (1.6% vs. 2.6%, P = 1.000), 90-day mortality (3.3% vs. 4.3%, P = 1.000), and incidence of postoperative complications (19.7% vs. 18.3%, P = 0.819). Overall survival at 1, 3, and 5 years was similar for obese patients (83.6%, 63.6%, 41.6%) as for non-obese patients (80.9%, 65.9%, 49.1%; P = 0.358). Disease-free survival at 1, 3, and 5 years was also similar for obese patients (71.5%, 36.3%, 24.3%) as for non-obese ones (60.2%, 43.7%, 27.7%; P = 0.969). CONCLUSION: Our propensity score-matched analysis strengthens the case that obesity does not adversely affect surgical outcomes of HCC patients undergoing curative hepatectomy.

COX-2 Promotes Migration and Invasion by the Side Population of Cancer Stem Cell-Like Hepatocellular Carcinoma Cells.

Cancer stem cells (CSCs) are thought to be responsible for tumor relapse and metastasis due to their abilities to self-renew, differentiate, and give rise to new tumors. Cyclooxygenase-2 (COX-2) is highly expressed in several kinds of CSCs, and it helps promote stem cell renewal, proliferation, and radioresistance. Whether and how COX-2 contributes to CSC migration and invasion is unclear. In this study, COX-2 was overexpressed in the CSC-like side population (SP) of the human hepatocellular carcinoma (HCC) cell line HCCLM3. COX-2 overexpression significantly enhanced migration and invasion of SP cells, while reducing expression of metastasis-related proteins PDCD4 and PTEN. Treating SP cells with the selective COX-2 inhibitor celecoxib down-regulated COX-2 and caused a dose-dependent reduction in cell migration and invasion, which was associated with up-regulation of PDCD4 and PTEN. These results suggest that COX-2 exerts pro-metastatic effects on SP cells, and that these effects are mediated at least partly through regulation of PDCD4 and PTEN expression. These results further suggest that celecoxib may be a promising anti-metastatic agent to reduce migration and invasion by hepatic CSCs.

Adjuvant transarterial chemoembolization after curative resection of hepatocellular carcinoma: propensity score analysis.

AIM: To compare survival and recurrence in hepatocellular carcinoma (HCC) patients who did or did not receive adjuvant transarterial chemoembolization (TACE). METHODS: A consecutive sample of 229 patients who underwent curative resection between March 2007 and March 2010 in our hospital was included. Of these 229 patients, 91 (39.7%) underwent curative resection followed by adjuvant TACE and 138 (60.3%) underwent curative resection alone. In order to minimize confounds due to baseline differences between the two patient groups, comparisons were conducted between propensity score-matched patients. Survival data and recurrence rates were compared using the Kaplan-Meier method. Independent predictors of overall survival and recurrence were identified using Cox proportional hazard regression. RESULTS: Among 61 pairs of propensity score-matched patients, the 1-, 2-, and 3-year overall survival rates were 95.1%, 86.7%, and 76.4% in the TACE group and 86.9%, 78.5%, and 73.2% in the control group, respectively. At the same time, the TACE and control groups also showed similar recurrence rates at 1 year (13.4% vs 24.8%), 2 years (30.6% vs 32.1%), and 3 years (40.1% vs 34.0%). Multivariate Cox regression identified serum alpha-fetoprotein level ≥ 400 ng/mL and tumor size > 5 cm as independent risk factors of mortality (P < 0.05). CONCLUSION: As postoperative adjuvant TACE does not improve overall survival or reduce recurrence in HCC patients, further study is needed to clarify its clinical benefit.