Primary Hepatocellular Carcinoma Patients Research Articles

Elaborating the Tumor Ecosystem of Primary and Relapsed Hepatocellular Carcinoma by Single-Cell RNA Sequencing

Hepatocellular carcinoma (HCC) has a high relapse rate and low 5-year survival rate. We generated > 20,000 full-length single-cell transcriptomes from 19 primary or relapsed HCC patients, determining unique features of the tumor microenvironment in relapsed as compared to primary HCC. Relapsed tumors have reduced regulatory T cells, and increased dendritic cells (DCs) and infiltrated CD8+ T cells. CD8+ T cells from relapsed tumors show group 2 innate lymphoid cell like state, with high naive, low cytotoxic and exhausted signals. The abundance of distinct DC subtypes is associated with good prognosis in primary or relapsed HCC, while FCN1+ monocytes are associated with poor prognosis only in relapsed HCC. Differentially expressed genes and interactions analyses reveal potential mechanisms driving immune evasion and tumor survival in relapsed and primary HCC. Together these results provide a compressive understanding of the ecosystem in primary and relapsed tumors, guiding future immune therapy strategies in HCC.

Stereotactic body radiation therapy in primary hepatocellular carcinoma: current status and future directions.

Stereotactic body radiation therapy (SBRT) is a form of radiation therapy that has been used in the treatment of primary hepatocellular carcinoma (HCC) over the past decade. To evaluate the clinical efficacy of SBRT in primary HCC, a literature search was conducted to identify original research articles published from January 2000 through January 2018 in PubMed on SBRT in HCC. All relevant studies published from 2004 to 2018 were included. Prospective studies demonstrated 2-year local control (LC) rates ranging from 64-95% and overall survival (OS) rates ranging from 34% (2-year) to 65% (3-year). Retrospective studies demonstrated 2-year LC rates of 44-90% and 2-year OS rates of 24-67%. Reported toxicities in primary HCC patients vary but SBRT appears to be relatively well tolerated. Studies comparing SBRT to radiofrequency ablation (RFA) are few, but they suggest SBRT may be more effective than RFA in specific primary HCC populations. Additionally, SBRT appears to increase the efficacy of both transarterial chemoembolization (TACE) and sorafenib in selected primary HCC populations.

Serum miR-130b level, an ideal marker for monitoring the recurrence and prognosis of primary hepatocellular carcinoma after radiofrequency ablation treatment

ObjectiveThis study was aimed to explore the potential roles of miR-130b for the efficacy of radiofrequency ablation (RFA) in patients with primary hepatocellular carcinoma (PHC). MethodsThe serum sample of 110 PHC patients, which underwent RFA treatment, was collected on 1d pre-operation (Pre 1), 7d (POD 7) and 14d post-operation (POD 14). qRT-PCR was used to detect miR-130b expression. The relationship between miR-130b expression and clinicopathological features, postoperative recurrence and survival rate were analyzed. ResultsThe liver function of PHC patients was improved after RFA treatment. The level of alpha fetoprotein (AFP) was gradually reduced on POD 7 and POD 14 (all P < 0.05). Before RFA, the expression of miR-130b in PHC patients was upregulated, while the expression of miR-130b decreased significantly with time after RFA treatment. And high expression of miR-130b was closely related to cirrhosis (P = 0.027) and tumor differentiation degree (P < 0.01). Serum miR-130b levels were significantly higher in patients with recurrence than in patients without recurrence (P < 0.05). Patients were divided into two groups according to miR-130b expression level (median ΔCt), compared with low ΔCt group, the incidence of recurrence in high ΔCt group was significantly higher after RFA (P = 0.020). Kaplan-Meier survival analysis showed that the survival rate of high ΔCt group was significantly shorter than that of low ΔCt group (P < 0.001). ConclusionOur study provided evidence that serum miR-130b level may be used as an ideal marker for monitoring the recurrence and prognosis of PHC after RFA treatment.

Comparison of Tissue-Link combined with Cusa and Pringle in hepatectomy for primary hepatocellular carcinoma

Objective To evaluate the clinical effect of Tissue-Link combined with Cusa and Pringle in hepatectomy for primary hepatocellular carcinoma. Methods From January 2013 to January 2017, the clinical data of ninety-six primary hepatocellular carcinoma patients who had received hepatectomy were collected.45 cases of hepatectomy (control group) were performed by Pringle.The other 51 cases (observation group) were treated with Tissue-Link combined with Cusa.The indexes and survival rates were compared between the two groups during and after operation. Results Compared with the control group, the operation time of the observation group was prolonged ((189.2±45.8) min vs.(151.6±34.7) min, t=-5.101), the intraoperative blood loss ((273.5±141.6) ml vs.(371.3±127.2) ml, t=7.396), total bilirubin at seventh days after the operation ((15.7±8.9) μmol/L vs.(26.5±10.8) μmol/L, t=5.320) and postoperative albumin supplementation((61.0±9.7) g vs.(84.6±9.3) g, t=7.698) of the observation group decreased.The tumor recurrence rate (0 vs.8.9% (4/45)), intrahepatic metastasis rate (7.8% (4/51) vs.20% (9/45)), extrahepatic metastasis rate (3.9% (2/51) vs.17.8% (8/45)) (χ2=.031, 6.315, 6.746) decreased and the differences were statistically significant (P<0.05). The 2 year and 3 year tumor free survival rate (88.2%, 76.5%) of the observation group was higher than those of the control group (64.4%, 44.4%, χ2=5.468, 8.902), and the total survival rate of 3 year after operation (80.4%) in the observation group was significantly, higher than that of the control group (51.1%, χ2=4.896), the difference was statistically significant (P<0.05). Conclusion Tissue-Link combined with Cusa is superior to Tissue-Link combined with Pringle in hepatectomy for primary hepatocellular carolnoma.It has less intraoperative blood loss, less damage to liver function and a lower relapse rate of ineisional margin, and the disease-free survival rate and overall survival rate are improved significantly. Key words: Primary hepatocellular carcinoma; Hepatectomy; Tissue-Link; Cusa

OP149 Survival Rates And Costs In Hepatocellular Carcinoma With Cirrhosis

Introduction:Early detection of primary hepatocellular carcinoma (PHC) patients with cirrhosis is critical to enhance PHC patients’ survival rates and to save medical costs. The study aimed to generate real world evidence to support the importance for early detection of PHC patients, and this evidence will contribute to a cost effectiveness analysis of the national liver cancer surveillance program.Methods:A retrospective analysis was performed on 98,275 PHC patients with cirrhosis in the National Center Cancer Registry from 2005 to 2014, linked to the Korea National Health Insurance claims database. The hazard ratio (HR) of mortality within five years and medical costs for the patients were compared by surveillance, epidemiology, and end results (SEER) stage.Results:There were differences in survival rates and medical costs depending on their characteristics including sex, age at diagnosis, SEER stage and types of initial treatment of cancer. The HR of mortality within five years of the PHC patients with distant stage versus local stage was 3.36 with 95% Confidence Interval (95% CI: 3.33–3.38) which is higher than those of the patients with regional stage (HR 1.93, 95% CI: 1.92–1.95). The estimated annual medical cost was USD 38,208 with standard deviation (SD) 54,399 for localized stage but USD 16,345 (SD 42,377) for distant stage.Conclusions:If PHC patients with cirrhosis were detected at early stage, their survival rates would be clinically better with a big saving for medical costs than if they were detected at distant stage. This result itself highlights that importance of the national liver cancer surveillance program. Future studies are indicated to apply these quantitative results into the cost-effectiveness analysis of the Korean national liver cancer surveillance program.

Serum AFU, 5'-NT and AFP as Biomarkers for Primary Hepatocellular Carcinoma Diagnosis.

To evaluate the clinical value of serum α-L-fucosidase (AFU), 5’-nucleotidase (5’-NT) and alpha fetoprotein (AFP) as biomarkers for primary hepatocellular carcinoma (PHC) diagnosis. Methods: Thirty six primary hepatocellular carcinoma (PHC) patients and 36 healthy controls were recruited in this study from February 2014 to January 2016 in the Second People’s Hospital of Tianjin. The serum level of AFU, 5’-NT and AFP were examined and compared between the two groups. The diagnostic sensitivity, specificity area under the receiver operating characteristic (ROC) curve were calculated by STATA11.0 software. Results: The serum level of AFU, 5’-NT, AFP were 30.87±10.43(U/L), 5.58±3.89(U/L), 233.60±226.60 (μg/L) respectively for primary hepatocellular carcinoma group and 19.96±6.73 (U/L), 1.87±0.84 (U/L), 16.64±14.17 (μg/L) for healthy control groups. The serum level of AFU, 5’-NT and AFP in primary hepatocellular carcinoma group were significant higher than those of healthy control group (P<0.001). The diagnostic sensitivity and specificity were 0.78 (95%CI:l0.61-0.90), 0.64 (95%CI:0.46-0.79) for serum AFU, 0.75(95%CI:0.58-0.88), 0.72(95%CI:0.55- 0.86) for serum 5’-NT and 0.72 (95%CI:0.55-0.86), 0.92 (95%CI:0.78-0.98) for serum AFP respectively. The AUC under the ROC curve were 0.80 (0.69-0.90), 0.80 (0.69-0.91) and 0.87 (0.780-0.96) for serum AFU, 5’-NT and AFP respectively. Positive correlation between AFU and 5’-NT (rpearson=0.63, P<0.05), AFU and AFP (rpearson=0.49, P<0.05), 5’-NT and AFP(rpearson=0.44, P<0.05) were found in the primary hepatocellular carcinoma patients. Conclusion: Serum AFU, 5’-NT and AFP were higher in PHC patients than those of healthy controls. The difference between PHC patients and healthy controls made serum AFU, 5’-NT and AFP potential biomarker for PHC diagnosis.

Value of detection of serum glypican-3 level in diagnosis and therapeutic effect evaluation of primary hepatocellular carcinoma

To explore the clinical value of detecting serum glypican-3 in the diagnosis and therapeutic effect evaluation of primary hepatocellular carcinoma (PHC). Using sandwich ELISA, we detected serum glypican-3 levels in 60 patients with PHC, 60 with metastatic liver cancer, 50 with liver cirrhosis, 50 with chronic viral hepatitis, 20 with hepatic cyst, 20 with fatty liver, 20 with hepatic hemangioma and 20 with drug-induced hepatitis as well as in 40 healthy subjects (control). We also analyzed the changes in serum levels of glypican-3 and alpha fetoprotein (AFP) in PHC patients after treatment. PHC patients had significantly higher serum levels of glypican-3 than patients with other liver diseases and the control subjects (P<0.05). The levels of serum glypican-3 were significantly higher in patients with metastatic liver cancer, liver cirrhosis and viral hepatitis than in those with other benign liver diseases and the control subjects (P<0.05). Glypican-3 level was not associated with AFP level or liver function in PHC patients, in whom the positivity rates for glypican-3 and AFP were 65% and 56.7%, respectively. The detection rate of PHC increased to 85% by a combined detection of AFP and glypican-3. In the 23 PHC patients who responded positively to treatments, serum glypican-3 level showed a steady decline compared with that in 15 patients before treatment, while serum AFP level showed a similar decrease only in 10 patients. Combined detection of glypican-3 and AFP is expected to improve the early diagnosis rate of PHC. The different thresholds of serum glypican-3 may play a role in the differential diagnosis of PHC and other various liver diseases. Glypican-3 may serve as a better marker than AFP with a high specificity and sensitivity for evaluating the therapeutic effect in PHC patients.

Clinical analysis of thymosin combined with liver protecting drugs in the treatment of primary hepatocellular carcinoma

Objective To investigate the clinical effect of thymosin combined with liver gland peptide drugs in the treatment of primary liver cancer. Methods 138 cases of primary hepatocellular carcinoma (HCC) were seleted as the research subjects, and they were divided into observation group (n=69) and control group (n=69) according to the number table method.The control group was treated with simple hepatoprotective drugs, the observation group was treated with thymosin on the basis of the control group.The clinical curative effect of the two groups, quality of life improvements were observed. Results In the observation group, the total effective rate was 81.16%, which in the control group was 43.47%, the difference was statistically significant between the two groups (χ2=8.362, P<0.05). The rate of life quality improvement of the observation group was 60.86%, which of the control group was 23.18%, there was statistically significant difference between the two groups (χ2=9.726, P<0.05). Conclusion The primary HCC patients treaed with thymosin combined with hepatoprotective drugs can effectively improve the patients' life quality, with good clinical curative effect, and it is worth clinical promotion and application. Key words: Liver neop; asms; Thymosin; Hepatoprotective drugs

Expression of muscle scinderin in primary hepatocellular carcinoma with portal vein tumor thrombus and its clinical significance

Objective To analyze the expression of muscle scinderin(SCIN) in primary hepatocellular carcinoma(HCC) with portal vein tumor thrombus(PVTT) and its clinical significance. Methods 46 primary HCC patients with PVTT were selected.All patients' carcinoma adjacent tissues, HCC tissues, PVTT tissues were collected.SCIN expression in three kinds of surgical specimen was detected by immunohistochemical staining, the results were compared.All patients were followed up for three years, the recurrence rate within half a year and 3-year mortality were compared. Results The positive expression rates of SCIN in carcinoma adjacent tissues, HCC tissues and PVTT tissues were 69.57%, 45.65%, 23.91%, which showed a decreasing trend.The relapsed within six months and 3-year mortality rate of the SCIN-negative patients were 85.71%, 95.24%, which were significantly higher than those of the SCIN-positive patients.The SCIN expression level was closely related to tumor size, with or without coating and alpha-fetoprotein level, the differences were statistically significant (χ2=0.000, 0.007, 0.035, all P<0.05). Conclusion The SCIN expression level in primary HCC patients with PVTT is low, and it can be used as a prognostic indicator for primary HCC patients with PVTT. Key words: Liver neoplasms; Portal vein tumor thrombus; Scinderin; Prognostic indicators

Coenzyme Q10 and Oxidative Stress: Inflammation Status in Hepatocellular Carcinoma Patients after Surgery.

(1) Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths worldwide, and surgical resection is the main treatment for HCC. To date, no published study has examined the status of coenzyme Q10 in patients with HCC after surgery. Thus, the purpose of this study was to investigate the correlations between the level of coenzyme Q10, oxidative stress, and inflammation in patients with HCC after surgery; (2) Methods: 71 primary HCC patients were recruited. Levels of coenzyme Q10, vitamin E, oxidative stress (malondialdehyde), antioxidant enzymes activity (superoxidase dismutase, catalase, and glutathione peroxidase), and inflammatory markers (high sensitivity C-reactive protein; tumor necrosis factor-α; and interleukin-6) were measured; (3) Results: Patients with HCC had a significantly lower levels of coenzyme Q10 (p = 0.01) and oxidative stress (p < 0.01), and significantly higher levels of antioxidant enzymes activities and inflammation after surgery (p < 0.05). The level of coenzyme Q10 was significantly positively correlated with antioxidant capacity (vitamin E and glutathione peroxidase activity) and negatively correlated with inflammation markers after surgery; (4) Conclusion: Hepatocarcinogenesis is associated with oxidative stress, and coenzyme Q10 may be considered an antioxidant therapy for patients with HCC, particularly those with higher inflammation after surgery.

Adjuvant transcatheter arterial chemoembolization after curative liver resection for hepatocellular carcinoma

Objective To study the effect of adjuvant transcatheter arterial chemoembolization (TACE) on intrahepatic recurrence after curative liver resection for primary hepatocellular carcinoma (PHC). Methods 130 PHC patients who underwent curative liver resection from June 2010 to February 2013 were selected and randomly allocated to the study group (n=67) and the control group (n=63). The study group underwent adjuvant TACE for 1~4 times, and the control group did not receive any adjuvant therapy. On follow-up for 36 months, the postoperative recurrence rates, tumour free survival time and tumor free survival rates of the two groups were compared. Results At 6 months after surgery, the serum AFP level [(379.8±91.7) μg/L vs. (414.5±84.3) μg/L] and the IGFBP-2 level [(2 855.3±727.5) μg/L vs. (3 259.6±894.1) μg/L] in the study group were significantly lower than the control group (P 0.05). The 3-year cumulative tumor free survival rate of the study group (81.0% vs. 73.2%) was significantly higher than the control group (P 0.05). The recurrent rates of patients who underwent TACE 1 time and those who did not receive TACE showed no significant difference (P>0.05). In patients who had TACE twice, the 1-year (4.3% vs. 28.6%), 2-year (15.2% vs. 41.3%) and 3-year (26.1% vs. 49.2) cumulative recurrence rates were significantly lower than patients who did not receive TACE (P 0.05). Conclusions Adjuvant TACE helped to reduce PHC recurrence after curative liver resection during the high-risk period for recurrence. A 1-time TACE did not significantly reduce postoperative recurrence rate, and ≥3 times TACE did not significantly improve tumor-free survival rates. Adjuvant TACE and the number of TACE should be reasonably carried out based on the indications and pathological characteristics. Key words: Hepatocellular carcinoma; Transcatheter arterial chemoembolization; Pathological characteristic; Prognosis

Decreased expression of protocadherin 20 is associated with poor prognosis in hepatocellular carcinoma.

Recently, protocadherin 20 has been reported as a tumor suppressor gene in hepatocellular carcinoma (HCC); however, the prognostic value of protocadherin 20 in HCC remains unclear. Hence, the purpose of this study was to investigate the clinical and prognostic values of protocadherin 20 in HCC patients. The expression of protocadherin 20 was assessed by quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry. Kaplan-Meier curves were created to calculate the overall survival of the patients, and Cox regression models were used to identify the risk factors associated with prognosis. Of 317 primary HCC patients, decreased expression of protocadherin 20 was observed in 184 (58.0%) patients (P < 0.001). Reduced protocadherin 20 protein expression correlated with portal hypertension, poor tumor differentiation, advanced Okuda stage, and Cancer of the Liver Italian Program score (all P < 0.05). Low protocadherin 20 expression was an independent risk factor for mortality (P = 0.018). Furthermore, in our newly developed simple risk score based on protocadherin 20, patients with total score > 1.11 showed significantly poorer outcome; and the predictive value of the score was better than the Barcelona Clinic Liver Cancer stage, Okuda stage, and Child-Pugh classification (Harrell's concordance index = 0.614). Taken together, these findings suggest that protocadherin 20 may represent a novel prognostic biomarker for HCC patients.

Alternative splicing of estrogen receptor alpha in hepatocellular carcinoma.

BackgroundThe role of estrogen receptor alpha (ERa), estrogen receptor beta (ERb) and ERa36 signaling in hepatocellular carcinoma (HCC) is not fully addressed.MethodsIn this study, three cohorts were included: (i) primary HCC patients (N = 76, cohort P), (ii) colorectal liver metastasis (mCRC) (N = 32, cohort S), and (iii) HCC from The Cancer Genome Atlas (TCGA) (N = 121). The levels of ERa36 and wtER36 were measured and their correlation with clinicopathologic features was determined.ResultsWtERa was downregulated and that ERa36 was upregulated in tumor tissues in both cohort P and TCGA data set. ERa36 was downregulated in tumor tissues in cohort S. In cohort P, wtERa was differentially expressed in gender (P < 0.000), age (P = 0.004), tumor number (P = 0.043), tumor size (P = 0.002), intrahepatic recurrence (P = 0.054). ERa36 was unequally expressed in different non-tumor liver status (P = 0.040). WtERa was negatively associated with overall survival (OS) and disease free survival (DFS) in cohort P. Compared with non-tumor tissues, the expression of ERa36 was increased in primary HCC but decreased in secondary HCC, showing opposite expression patterns of ERa36 between primary HCC and secondary HCC.ConclusionsPrimary HCC is associated with the decreased WtERa but increased ERa36. The expression pattern of ERa36 is different between primary HCC and secondary HCC, as the former with the increased ERa36 but the latter with the decreased ERa36. Therefore, the expression of ERa36 may be used to differentiate the primary HCC and the secondary one.

A multivariable model to predict survival for patients with hepatic carcinoma or liver metastasis receiving radiotherapy.

New parameters that correlate with overall survival were identified in patients with liver lesions treated with radiation therapy. Pretreatment information and parameters of radiation treatment plans for 129 metastatic and 66 hepatocellular carcinoma liver cancer patients were analyzed. Study end points included overall survival collected from patient charts and electronic records. Two practical nomograms were constructed for primary hepatocellular carcinoma and liver metastasis patients. For patients with a Child-Pugh A, radiation dose escalation provided a significant survival benefit. However, for those with Child-Pugh B or C, increasing dose does not impact on survival. The developed models can potentially guide dose selection and provide prognostic information but still require external validation.

Aldo-keto Reductase Family 1 Member B 10 Mediates Liver Cancer Cell Proliferation through Sphingosine-1-Phosphate.

AKR1B10 is involved in hepatocarcinogenesis via modulation of fatty acid and lipid synthesis. AKR1B10 inhibition results in apoptosis of tumor cells whose lipids, especially phospholipids, were decreased by over 50%, suggesting involvement of phospholipids like sphingosine-1-phosphate (S1P) in AKR1B10’s oncogenic function. Using a co-culture system, we found that co-culture of QSG-7701 (human hepatocyte) with HepG2 (hepatoma cell line) increases QSG-7701’s proliferation, in which AKR1B10-S1P signaling plays a pivotal role. Consistent with previous findings, AKR1B10 mRNA and protein levels were higher in primary hepatocellular carcinoma (PHC) tissues than in peri-tumor tissues. Interestingly, the level of S1P was also higher in PHC tissues than in peri-tumor tissues. After analyzing the correlation between AKR1B10 mRNA expression in PHC tissues and the clinical data, we found that AKR1B10 mRNA expression was associated with serum alpha-fetoprotein (AFP), tumor-node-metastasis (TNM) stage, and lymph node metastasis, but not with other clinicopathologic variables. A higher AKR1B10 mRNA expression level is related to a shorter DFS (disease free survival) and OS (overall survival), serving as an independent predictor of DFS and OS in PHC patients with surgical resection.

Randomized clinical trial of the effect of simo decoction plus acupuncture and chewing gum on postoperative ileus in patients with hepatocellular carcinoma after hepatic resection.

307 Background: Postoperative ileus (POI) is a common complication following hepatic resection that delays recovery of bowel function and increases length of hospital stay. Simo decoction (SMD) and acupuncture tsusanli acupoint are used to enhance bowel hypomotility in China. Chewing gum reducing POI is reported. The aim of study is to evaluate the effect of SMD plus acupuncture tsusanli acupoint and chewing gum alone on POI and length of hospital stay in patients with hepatocellular carcinoma (HCC) after hepatic resection. Methods: Primary HCC patients undergoing hepatic resection were randomized to SMD plus acupuncture, chewing gum, or empty control group. Interventions were started on postoperative day 1 for six consecutive days or until flatus. Primary endpoints were POI and length of hospital stay. Secondary endpoints were surgical complications. Results: Between March 2015 and August 2015, 162 patients were randomized to SMD plus acupuncture (55), chewing gum (53), or empty control (54). SMD plus acupuncture or chewing gum group have significantly shorter first peristalsis, flatus, and defaecation time than empty control group (all P&lt; 0.05). The mean (s.d.) length of hospital stay of the three groups was 14.0 (4.9), 14.7 (6.2), and 16.5 (6.8) days. The difference between SMD plus acupuncture and empty control group was significant (P = 0.014). However, chewing gum cannot significantly shorten hospital stay than empty control (P = 0.147). Interventions groups had less grade I and II complications. Conclusions: SMD plus acupuncture or chewing gum is a safe treatment to reduce POI and shorten hospital stay. Registration number: NCT02438436 (https://clinicaltrials.gov). Clinical trial information: NCT02438436.

索拉非尼联合TACE术治疗中晚期原发性肝癌不良反应的观察及护理

Objective: To observe the adverse reactions induced by sorafenib plus TACE for the treatment of advanced primary hepatocellular carcinoma (HCC) adverse reactions, and related nursing countermeasures. Methods : Advanced HCC patients in the South Hospital, from January 2014 to December 2014, were selected and treated with sorafenib plus TACE. Liver functions in all patients were Class A or B grade, and accept TACE and sorafenib therapy. Observe the adverse reactions, take corresponding nursing measures according to its characteristics and examine the treatment effect. Results: We found that all patients can appear different degrees of adverse reactions in the treatment process. The most common is hand foot skin reaction, fever, pain, the occurrence probability more than 70%, and some patients may have nausea, vomiting, rash, fatigue and other adverse reactions. The corresponding nursing measures and preventive measures achieved good treatment effect. Conclusion: A full assessment of the data of advanced primary hepatocellular carcinoma patients is needed prior to sorafenib plus TACE treatment. Moreover, close observation of the side reaction and timely effective nursing measures, can help patients complete the combined treatment and achieve a better therapeutic effect.

Ezrin expression in the primary hepatocellular carcinoma patients and associated with clinical, pathological characteristics.

The aim of this study was to assess Ezrin expression in the primary hepatic carcinoma patients and associated with clinical, pathological characteristics. Fifty-one patients with primary hepatocellular carcinoma (PHC) with completed clinical data were retrospectively analyzed in this study. The Ezrin expression in PHC and normal control liver tissue was tested by immunohistochemical assay. The Ezrin expression and relationship with clinical characteristics were evaluated. The Ezrin positive rate were 66.7% and 15.7% with expression score of 3.21 ± 1.46 and 0.60 ± 1.10, respectively, in the cancer tissue and control tissue with statistical difference (P < 0.05). The Ezrin expression was associated with the metastasis status of the patients (P < 0.05) but not associated with the age (P > 0.05), gender (P > 0.05), differentiation (P > 0.05), and tumor diameter (P > 0.05). Ezrin protein is highly expressed in human PHC tissue which can be used for the prediction of metastasis disease.

Prognostic Value of Pre-Operative Platelet to Lymphocyte Ratio in Patients with Resected Primary Hepatocellular Carcinoma.

The platelet to lymphocyte ratio (PLR) is a readily available cancer biomarker but its prognostic value for patients with resected primary hepatocellular carcinoma (HCC) is uncertain. Thus, we investigated the relationship between PLR and survival of patients with resected primary HCC in the Fujian area, a high occurrence area of HCC in China. This retrospective study included 337 patients with primary HCC who underwent surgical removal of primary liver cancer between 2004 and 2012 in Fuzhou General Hospital in Fujian, China. Pre-operative peripheral blood PLR was measured by platelet counts divided by lymphocyte counts. PLR and clinical factors were associated with a X2 test and data were analyzed with a Kaplan-Meier plus log rank analysis. Independent prognostic factors related to survival were assessed with multivariable analysis. Subjects were classified by a median PLR value of 91 (low: ≤ 91, n = 169 and high: > 91, n = 168). HighPLR patients died more often (57.7% vs. 35.5%, p = 4.3 x 10-5 and 39 months vs. 88 months, p < 0.001, respectively) and high PLR was associated with a nearly 2-fold elevated death risk (hazard ratio [HR]:1.815, 95% confidence interval (CI): 1.298 - 2.537, p = 4.85 x 10-4). Serum AFP, TNM stage and tumor size were also independent prognostic factors for patients with resected primary HCC according to multivariable analysis. PLR may be useful as a biomarker for assessing survival of resected primary HCC patients.

Radiofrequency ablation-increased CXCL10 is associated with earlier recurrence of hepatocellular carcinoma by promoting stemness.

Radiofrequency ablation (RFA) represents a valuable choice in hepatocellular carcinoma (HCC); however, local recurrence of HCC is common after RFA. Here, 20 primary HCC patients treated by RFA were enrolled. Before (termed 0d) and after RFA treatment for 1 and 7days (termed 1d and 7d, respectively), plasma and noncancerous tissue were collected. ELISA assay showed that plasma C-X-C motif chemokine 10 (CXCL10) was increased in ten patients (type I patients) but decreased in the other 10 patients (type II patients). The mean interval for HCC recurrence in type I patients was less than the mean interval in type II patients. Interestingly, a significant negative correlation between interval for HCC recurrence and fold change of plasma CXCL10 (1d/0d or 7d/0d) was identified, suggesting that RFA-induced CXCL10 is associated with earlier HCC recurrence. Immunofluorescence assay showed that the receptor of CXCL10, chemokine (C-X-C motif) receptor 3 (CXCR3), was significantly increased in type I, but not type II, patients after RFA. In vitro assay demonstrated that CXCL10 stimulus increased the rate of CD133(+) cancer stem cells (CSCs) in HepG2 cells by binding to CXCR3 and then inducing c-Myc expression. Many studies have reported that induction of CD133(+) CSCs contributes to HCC recurrence. Thus, CXCL10-increased CD133(+) CSCs by activating CXCR3/c-Myc pathway might accelerate HCC recurrence after RFA. These data might have potential implications for HCC therapy.