Liping Zhuang

A novel systemic inflammation response index (SIRI) for predicting the survival of patients with pancreatic cancer after chemotherapy

Predicting survival is uniquely difficult in patients with pancreatic cancer who receive chemotherapy. The authors developed a systemic inflammation response index (SIRI) based on peripheral neutrophil, monocyte, and lymphocyte counts and evaluated the ability of the SIRI to predict the survival of patients with pancreatic cancer who received chemotherapy.

Hepatocellular carcinoma cell lines retain the genomic and transcriptomic landscapes of primary human cancers

Hepatocellular carcinoma (HCC) cell lines are useful in vitro models for the study of primary HCCs. Because cell lines acquire additional mutations in culture, it is important to understand to what extent HCC cell lines retain the genetic landscapes of primary HCCs. Most HCC cell lines were established during the last century, precluding comparison between cell lines and primary cancers. In this study, 9 Chinese HCC cell lines with matched patient-derived cells at low passages (PDCs) were established in the defined culture condition. Whole genome analyses of 4 HCC cell lines showed that genomic mutation landscapes, including mutations, copy number alterations (CNAs) and HBV integrations, were highly stable during cell line establishment. Importantly, genetic alterations in cancer drivers and druggable genes were reserved in cell lines. HCC cell lines also retained gene expression patterns of primary HCCs during in vitro culture. Finally, sequential analysis of HCC cell lines and PDCs at different passages revealed their comparable and stable genomic and transcriptomic levels if maintained within proper passages. These results show that HCC cell lines largely retain the genomic and transcriptomic landscapes of primary HCCs, thus laying the rationale for testing HCC cell lines as preclinical models in precision medicine.

Hepatocellular Carcinoma More Than 3 cm in Diameter: A Systematic Review of Transcatheter Arterial Chemoembolization Plus Percutaneous Ethanol Injection versus Transcatheter Arterial Chemoembolization Alone

Objective. To identify the efficiency and safety of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol (PEI) for patients with hepatocellular carcinoma (HCC) more than 3 cm in diameter in comparison with those of transcatheter arterial chemoembolization monotherapy. Methods. All databases were searched up to February 22, 2013. The literature retrieval was conducted through Pubmed, Web of Science, and Cochrane Library. We also searched Chinese databases, including Chinese National Knowledge Infrastructure (CNKI), Chinese Biology Medicine (CBM), Wanfang database, and VIP Database for Chinese Technical Periodicals without language limitations. Results. Based on the criteria, we found 12 RCTs including 825 patients. Our results showed that TACE combined with PEI therapy compared with TACE monotherapy improved overall survival and tumor response. Conclusion. The combination of TACE and PEI compared with TACE monotherapy improved overall survival rates and tumor response of patients with large HCC. Besides, larger and more methodologically rigorous clinical trials are needed to confirm this outcome.

Na + /K + -ATPase α1 subunit, a novel therapeutic target for hepatocellular carcinoma

We aimed to identify the expression patterns of Na+/K+-ATPase (NKA) α subunits in human hepatocellular carcinoma (HCC) samples and evaluate these subunits as potential targets for HCC treatment. The mRNA expression profiles of NKA α subunits in human HCC samples were analyzed. We found that the mRNA expression for NKA α1 subunit (ATP1A1) was higher than that for other NKA α subunits. Also, ATP1A1 gene expression was markedly higher in HCC samples than in adjacent nontumor tissue samples. Western blotting data suggested that 6 of 14 (43%) HCC samples had elevated ATP1A1 protein expression. Furthermore, knockdown of ATP1A1 expression in human HCC HepG2 and MHCC97H cells markedly reduced their proliferation in vitro and suppressed the tumorigenicity of MHCC97H cells in vivo. Downregulation of ATP1A1 expression resulted in cell-cycle arrest at G2/M phase and apoptosis in HepG2 cells as well as decreased migration in Hep3B cells. We further validated that ATP1A1 downregulation caused intracellular accumulation of reactive oxygen species. Pretreatment with N-acetyl cysteine blocked cell-growth inhibition induced by ATP1A1 downregulation. Collectively, these data suggested that targeting ATP1A1 is a novel approach to the treatment of HCC.

Prognostic nutritional index serves as a predictive marker of survival and associates with systemic inflammatory response in metastatic intrahepatic cholangiocarcinoma

Objective The significance of the prognostic nutritional index (PNI) has been widely reported and confirmed in many types of cancers. However, few studies are available indicating its prognostic power in patients with intrahepatic cholangiocarcinoma (ICC). Thus, we investigated its relationship with overall survival (OS) to evaluate its role in predicting survival in patients with ICC. Patients and methods Between October 2011 and October 2015, 173 consecutive patients with pathologically confirmed locally advanced or metastatic ICC were enrolled. First, the correlations between PNI and clinical factors were analyzed among these patients. Next, univariate and multivariate analyses were conducted to evaluate the association between PNI and OS among these patients with ICC. In addition, the relationships between PNI and three typical systemic inflammatory response (SIR) markers – the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR), and the lymphocyte/monocyte ratio (LMR) – were also assessed. Results A lower PNI was linked with a shorter OS in patients with ICC, as reflected obviously in the Kaplan–Meier analyses. The patients with ICC were divided into the locally advanced group and the metastatic group. Further analyses revealed that PNI is not associated with OS in the locally advanced group. However, in the subgroup of patients with metastatic ICC, a lower PNI significantly correlated with a worsened OS. The OS for patients with a low PNI is 5 months, whereas the OS is 10.17 months for patients with a high PNI. Multivariate analyses revealed that PNI is independently correlated with OS. We finally proved that PNI is negatively proportional to NLR and PLR and positively proportional to LMR. Conclusion Our results demonstrate that decreased PNI signifies a poor OS and is associated with SIR in patients with metastatic ICC. Therefore, it may serve as a valuable predictive marker in patients with metastatic ICC.

Serum liver enzymes serve as prognostic factors in patients with intrahepatic cholangiocarcinoma

Objective Liver functions, reflective of the overall status of the host, have been reported to be important factors affecting the prognosis in many types of cancers. In this study, we explored the influences of liver enzymes albumin (ALB), globulin (GELO), total protein (TP), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), gamma glutamyltranspeptidase (GGT), and lactate dehydrogenase (LDH) on the overall survival (OS) in a number of 173 patients with intrahepatic cholangiocarcinoma (ICC). Patients and methods Between 2011 and 2015, we enrolled patients with pathologically proven locally advanced or metastatic ICC. The impact of ALB, GELO, TP, ALP, ALT, AST, TBIL, DBIL, GGT, and LDH on OS were analyzed using Kaplan–Meier analysis. Next, the associations between these liver enzymes and OS were evaluated by univariate and multivariate analyses. Finally, the role of these enzymes in OS was evaluated in the subgroups. Results Elevated liver enzymes were linked with OS. We revealed that independent prognostic factors of poor outcome were ALP, TBIL, DBIL, and GGT, whereas ALB is a protective factor in ICC patients. Conclusion Our results demonstrate that these liver enzymes may serve as valuable predictive markers in ICC patients.

Carbonic anhydrase 2 inhibits epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma

Carbonic anhydrase 2 (CA2) plays vital role in the regulation of ion transport and pH balance and is involved in many biological processes; however, its role in cancer remains obscure. In this study, we identified a novel function of CA2 in facilitating hepatocellular carcinoma (HCC) metastasis. CA2 expression was elevated in Na+-K+-ATPase α1 (ATP1A1)-downregulated HCC cells and was inversely correlated with that of ATP1A1 in HCC. ATP1A1 acted as an oncoprotein whereas CA2 overexpression inhibited cell migration and invasion by reversing epithelial-mesenchymal transition (EMT) in HCC. CA2 downregulation promoted HCC metastasis and invasion whereas ATP1A1 downregulation inhibited HCC metastasis. Because of the opposing effects of CA2 and ATP1A1 in HCC, we examined the role of their correlation in HCC metastasis. CA2 attenuated ATP1A1-triggered tumor growth in vivo and ATP1A1-induced metastasis in vitro. Taken together, the present results suggest that CA2 serves as a suppressor of HCC metastasis and EMT and is correlated with favorable overall survival (OS) in HCC patients.

Jian Pi Li Qi Decoction Alleviated Postembolization Syndrome Following Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma A Randomized, Double-Blind, Placebo-Controlled Trial

Objective. To evaluate the effectiveness of Jian Pi Li Qi (JPLQ) decoction in improving quality of life of patients with hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE). Methods. A randomized, double-blind, placebo-controlled trial was conducted. A total of 150 patients with HCC were randomly assigned into 3 groups. Groups were designed as follows: neither herbal medicine nor placebo administration (group A), placebo treatment (group B), and JPLQ decoction treatment (group C). The measurement methods of the observed outcomes include MD Anderson Symptom Inventory–Gastrointestinal module, armpit temperature, and laboratory tests. Results. Among the 140 patients studied, the 12 symptoms rated as most severe, which characterize postembolization syndrome (PES), were fever, pain, fatigue, nausea, disturbed sleep, distress, lack of appetite, drowsiness, dry mouth, vomiting, constipation, and feeling bloated. All these increased significantly (all P < .05) after TACE; 7 symptoms, including fever, pain, fatigue, lack of appetite, drowsiness, dry mouth, and constipation (all P < .05), were found to be relieved significantly by JPLQ. JPLQ also improved the liver function damage caused by TACE. Conclusion. JPLQ decoction may be an effective modality to relieve PES and protect liver function in patients with HCC after TACE.

Systemic inflammation response index (SIRI) predicts prognosis in hepatocellular carcinoma patients

The systemic inflammation response index (SIRI) is a useful tool for predicting prognosis in some types of cancer. In this retrospective study, we evaluated the efficacy of SIRI in predicting overall survival in hepatocellular carcinoma (HCC) patients following local or systemic therapy. A cutoff value of 1.05 was identified for SIRI using ROC analysis in a training patient cohort. In the validation cohort, survival analysis revealed that median overall survival was longer in HCC patients with SIRI scores < 1.05 than in those with scores ≥ 1.05. Cox analysis of the validation cohort demonstrated that SIRI was associated with overall survival and was more predictive of overall survival that the AFP level or Child-Pugh score. However, SIRI and Barcelona Clinic Liver Cancer (BCLC) stage were equally effective for predicting survival. In addition, HCC patients with BCLC stage C had higher SIRI scores and poorer overall survival. SIRI also correlated with liver function parameters. Thus SIRI may be a convenient, low cost and reliable tumor marker for predicting prognosis in HCC patients.

Role of monocyte-to-lymphocyte ratio in predicting sorafenib response in patients with advanced hepatocellular carcinoma

Purpose Sorafenib is the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC), and its clinical response rate is only about 10%. In clinical practice, some HCC patients obtain favorable overall survival (OS) to the treatment of sorafenib while some patients do not demonstrate a sensitive response to sorafenib. Therefore, it is valuable to determine the subgroups of patients who respond well as well as poorly to sorafenib. Thus, clinical variables of advanced HCC patients with sorafenib treatment were compiled to investigate whether monocyte-to-lymphocyte ratio (MLR) could be a biomarker for predicting sorafenib response. Patients and methods In this study, a total of 142 patients with advanced HCC were enrolled from January 1, 2013 to December 31, 2016 at the Fudan University Shanghai Cancer Center. MLR was analyzed using a ROC curve. A Cox regression model and log-rank test were performed to analyze the relationship between clinical factors and OS, as well as progression free survival (PFS). Results The optimal cut-off point for MLR was 0.35, and MLR level had no significant correlation with age, gender, hepatitis B infection, grade, alpha-fetoprotein (AFP) level and state of portal vein tumor thrombus. Multivariate Cox regression model showed that grade (HR: 0.608, 95% CI: 0.409–0.904, P=0.014), AFP (HR: 0.445, 95% CI: 0.307–0.645, P=0.0001), MLR (HR: 0.445, 95% CI: 0.301–0.658, P=0.0001) and aspartate aminotransferase (AST) (HR: 1.005, 95% CI: 1.001–1.009, P=0.007) may serve as independent prognostic predictors for OS, and MLR maintained significant correlation with PFS in HCC patients (HR: 0.457, 95% CI: 0.308–0.678, P=0.0001). By log-rank test, there was longer PFS and OS in patients with low MLR than in those with high MLR (both P=0.0001). Conclusion MLR can predict sorafenib response and a high MLR is correlated with poor prognosis in patients with advanced HCC.