Overexpression of SSR2 promotes proliferation of liver cancer cells and predicts prognosis of patients with hepatocellular carcinoma.

Signal Sequence Receptor Subunit 2 (SSR2) is a key endoplasmic reticulum gene involved in protein folding and processing. Previous studies found that it was upregulated in several cancers, but its precise role in hepatocellular carcinoma (HCC) remains unclear. To have a better understanding of this gene in HCC, we examined the expression of SSR2 in HCC tissues by analysing The Cancer Genome Atlas (TCGA) data and immunohistochemistry. We also assessed the association between SSR2 expression and clinicopathological characteristics of HCC patients and patient survival. Potential function of SSR2 was predicted through GSEA and protein-protein interaction analysis. MTT, flowcytometry, transwell and a nude mice xenograft model were employed to investigate the biological functions in vivo and in vitro. The results showed that the expression of SSR2 was significantly increased in HCC tissues, and SSR2 expression was associated with several clinical characteristics. In addition, patients with higher SSR2 expression had poorer survival. Enrichment analysis suggested that SSR2 was probably involved in biological process or signalling pathways related to G2/M checkpoint, passive transmembrane transporter activity, ATF2_S_UP. V1_UP and ncRNA metabolic process. Further experimental study showed that SSR2 knockdown inhibited cell proliferation, migration and invasion ability and promoted apoptosis and cell cycle arrest in vitro. Moreover, downregulation of SSR2 also repressed the growth of HepG2 cells in vivo. In conclusion, our study suggests that SSR2 may act as an oncogene in HCC.

Efficacy and safety of transarterial chemoembolization plus sorafenib in patients with recurrent hepatocellular carcinoma after liver transplantation.

Objectives: To explore the benefit and safety of transarterial chemoembolization (TACE) in combination with sorafenib in patients with recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). Methods: In this multi-center retrospective study, 106 patients with recurrent HCC after OLT were included. Fifty-two patients were treated with TACE plus sorafenib (TS group) and 54 were treated with TACE alone (TC group). Primary and secondary endpoints including overall survival (OS) and progression-free survival (PFS), and safety were assessed. Results: The median OS (17 vs 10 months, P=0.035) and PFS (12 vs 6 months, P=0.004) in the TS group were longer than those in the TC group. On multivariate analysis, BCLC stage (HR [hazard ratio]=0.73 [95% CI, 0.27-0.99], P=0.036) and sorafenib medication (HR=2.26 [95% CI, 1.35-3.69], P=0.01) were identified as independent prognostic risk factors for OS. No severe adverse events related to sorafenib were noted in the TS group. Four patients discontinued sorafenib due to intolerance. Conclusion: TACE in combination with sorafenib is a feasible regimen to improve the survival with mild toxicity in patients with recurrent HCC after OLT.

High mRNA Expression of CENPL and Its Significance in Prognosis of Hepatocellular Carcinoma Patients.

Centromere proteins (CENPs) are the main constituent proteins of kinetochore, which are essential for cell division. In recent years, several studies have revealed that several CENPs were aberrantly expressed in hepatocellular carcinoma (HCC). However, numerous centromere proteins have not been studied in HCC. In this study, we used databases of Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), the Kaplan-Meier Plotter, cBioPortal, the Human Protein Atlas (HPA), and TIMER (Tumor Immune Estimation Resource) and immunohistochemical staining of clinical specimens to investigate the expression of 15 major centromere proteins in HCC to evaluate their potential prognostic value. We found that the mRNA levels of 4 out of 15 centromere proteins (CENPL, CENPQ, CENPR, and CENPU) were significantly higher in HCC than in normal tissues, and their mRNA levels were associated with the tumor stages (p values < 0.01). Patients with higher mRNA levels of CENPL had poorer overall survival, progression-free survival, relapse-free survival, and disease-specific survival (p values < 0.05). Furthermore, the higher levels of CENPL mRNA were associated with worse overall survival in males without hepatitis virus infection (p values < 0.05). The protein expression level of CENPL in human HCC tissue was higher than that in normal liver tissue. In addition, the expression of CENPL was positively correlated with the levels of the tumor-infiltrating lymphocytes. The results suggest that the high mRNA expression of CENPL may be a potential predictor of prognosis in HCC patients.

Tenofovir and telbivudine combination therapy rapidly decreases viral loads in immune-tolerant chronic hepatitis B patients awaiting assisted reproduction: an open-label, randomized, controlled study.

BACKGROUND: Immune-tolerant chronic hepatitis B (CHB) patients awaiting assisted reproduction (AR) are required to initiate antiviral therapy because of laboratory safety concerns. The antiviral therapy in this group has not been well assessed. We sought to explore the efficacy and safety of the combination therapy (COM) of tenofovir (TDF) and telbivudine (LdT). PATIENTS AND METHODS: In this open-label, randomized, controlled study, we enrolled and randomized hepatitis B virus e-antigen (HBeAg)-positive CHB patients awaiting AR into the study COM group and the control (TDF) group. The COM group received combination therapy of TDF and LdT, and the TDF group received a single treatment of TDF. The patients were followed up for at least 48 weeks. The primary endpoint was the proportion of patients with undetectable HBV DNA level at week 12. RESULTS: A total of 121 patients were recruited into the COM group (n=60) and the TDF group (n=61). The percentages of patients with undetectable HBV DNA levels were 90.0% (54/60) in the COM group and 67.2% (41/61) (P=0.002) in the TDF group at week 12; the percentages were 96.6% (58/60) in the COM group and 85.2% (52/61) in the TDF group at week 48 (P=0.028), respectively. HBeAg seroconversion occurred in 5/60 (8.3%) patients in the COM group and 2/61 (3.3%) patients in the TDF group at week 48 (P=0.233). CONCLUSION: TDF and LdT combination therapy shows a rapid antivirological response in immune-tolerant CHB patients awaiting AR, which provide an alternative for this group at AR centers. However, the HBeAg seroconversion rate is unsatisfactory in the short term.

Bone marrow-derived mesenchymal stem cells promote hepatic regeneration after partial hepatectomy in rats.

OBJECTIVES: Our goal was to study the ability of mesenchymal stem cells (MSCs) to stimulate liver regeneration after partial hepatectomy in rats. METHODS: MSCs were isolated from bone marrow and cultured in vitro. Their characteristics were analyzed by flow cytometry. After 70% partial hepatectomy, Sprague-Dawley rats were randomly divided into three groups: a control group that was injected with saline, animals that received bone marrow-derived MSCs (BM-MSCs) by tail vein injection (the BM-MSC-TV group) and animals that received BM-MSCs by portal vein injection (the BM-MSC-PV group). The injected BM-MSCs were traced by labeling with 4',6-diamidino-2-phenylindole, and cell proliferations were determined by immunohistochemical staining with Ki-67 and 5-bromo-2'-deoxyuridine. RESULTS: After the third passage, the cultured BM-MSCs had a fibroblast-like morphology and expressed high levels of stem cell markers CD29 and CD90. The levels of albumin rose significantly in the BM-MSC-TV and BM-MSC-PV groups compared with the control group. The number of 4',6-diamidino-2-phenylindole-positive liver cells in the BM-MSC-PV group was significantly higher than in the BM-MSC-TV group. The levels of Ki-67 and 5-bromo-2'-deoxyuridine were significantly higher in the BM-MSC-TV and the BM-MSC-PV groups than in the controls. CONCLUSION: Taken together, these results indicate that BM-MSC injections enhance liver regeneration after partial hepatectomy in rats.