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PDF file - 824K, Knockdown of RNF43 affects the expression of MMPs. HepG2 and SMMC-7721 cells were transfected with indicated siRNAs. Seventy-two hours after transfection, cells were harvest and the expression of specific MMPs was detected by Western blotting.

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PDF file - 16459K, RNF43 expression in human Hepatocellular carcinoma tissues. Representative images (magnification � 100) of RNF43 stained tumors with (A) more than 75% positive tumor cells (+2), (B) 5-75% positive tumor cells (+1), and (C) less than 5% RNF43-positive tumor cells (0). (D) Adjacent noncancerous liver tissues.

PDF file - 140K, Primer sequences, Primary antibodies, and Differentially expressed genes after RNF43 knockdown

PDF file - 6281K, Knockdown of RNF43 inhibits invasion, migration and ECM adhesion of HCC Cells. Cells were transfected with indicated siRNAs. Seventy-two hours after transfection, the impact of RNF43 knockdown on invasion, migration and ECM adhesion was evaluated. (A) Representative images showing decreased migration in RNF43 siRNA-transfected HCC cells. (B) Representative images of wound-healing experiments. (C) The impact of RNF43 knockdown on adhesion of SMMC-7721 cells to different extracellular matrix proteins (n=3, **p < 0.01). (D) Knockdown of RNF43 inhibited the expression of Integrin β4. (E) Knockdown of RNF43 showed no effect on E-cadherin expression.

PDF file - 392K, Knockdown of RNF43 induces apoptosis in HCC cells. (A) At 72 hours after transfection with indicated siRNAs, the effect of RNF43 knockdown on cell apoptosis was assessed by flow cytometry using Annexin V/PI Apoptosis Kit (n=3, **p < 0.01, ***p < 0.001). (B) Protein expression of activated Caspase-3 was evaluated by Western blotting.

PDF file - 7954K, Histology and IHC analysis of HCC xenografts. (a, b) Hematoxylin-eosin-stained sections of xenograft tumors (magnification �400). Mitotic cells (arrows) were quantified in five randomly chosen high-power fields (n=5, *p = 0.04). (c, d) CD31 stained sections of xenograft tumors (Original magnification �200). Microvessels (arrows) were quantified in five randomly chosen high-power fields (n=5, *p = 0.01). (e, f) Tumor sections measured by TUNEL staining (Original magnification �200). TUNEL-positive cells (arrows) were quantified in 5 randomly chosen high-power fields (n=5, *p = 0.03). (g, h) RNF43 stained sections of xenograft tumors.

PDF file - 204K, Effects of siRNAs on RNF43 mRNA expression. HepG2 and SMMC-7721 cells were transfected with RNF43 siRNAs (RNF43-si1, -si2, and -si3), negative control siRNAs (siNC), or Mock-transfected (Mock). RNF43 mRNA expression was measured by qRT-PCR 48 hours after transfection.

PDF file - 266K, Gene Ontology analysis of differentially expressed genes after RNF43 Knockdown. Gene Ontology analysis was performed using EASE software, the bar indicates if the gene is up- (white) or down- (black) regulated after RNF43 knockdown.

Glycogen synthase encoding genes GYS1 and GYS2 are aberrantly expressed and play a vital role in progression of multiple malignancies. However, the clinical significance and biological function of GYS1 and GYS2 in hepatocellular carcinoma remain little known. The present study aims to evaluate the relationship of GYS1 and GYS2 expression with clinicopathologic characteristics, prognostic pattern and immune infiltration in hepatocellular carcinoma (HCC) using the data from The Cancer Genome Atlas (TCGA). The expression of GYS1 and GYS2 in HCC and normal liver tissues were primarily compared using TCGA data and further validated by another independent cohort from the gene expression omnibus (GEO) database and human protein atlas (HPA). Wilcoxon rank sum test, Chi-square test and logistical regression analysis were used to examine the relationship of GYS1 and GYS2 expression with clinicopathological features. Gene ontology (GO) term analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene set enrichment analysis (GSEA) were conducted to explain the enrichment pathways and underlying molecular mechanism for GYS1 and GYS2. Kaplan-meier analysis, Cox regression and nomograms were used to evaluate the predictive value of GYS1 and GYS2 expression on clinical outcomes in HCC. Receive operating characteristic (ROC) curve was performed to illustrate the correlation of GYS1 and GYS2 expression with the risk of HCC. In addition, the relationship of GYS1 and GYS2 expression with immune infiltrate cells and immune checkpoint related genes were analyzed. Higher GYS1 expression and lower GYS2 expression were examined in HCC than in normal liver tissue and prominently associated with AFP level, tumor stage, histologic grade, pathologic stage and unfavorable overall survival (OS). ROC analysis showed that GYS1 and GYS2 may serve as reasonable diagnostic biomarkers for HCC patients. Moreover, GYS1 expression and GYS2 expression were significantly correlated with abundance of immune infiltrate cells and level of immune checkpoint related genes. Function annotation disclosed that both GYS1 and GYS2 were probably involved in synapse membrane, potassium ion transport, passive transmembrane transporter activity, channel activity, synaptic membrane, transport complex, neuroactive ligand-receptor interaction, allograft rejection, E2F targets, epithelial mesenchymal transition, G2M checkpoint and KRAS signaling pathway. The current study demonstrated that GYS1 upregulation and GYS2 downregulation might reshape tumor immune microenvironment and contribute progression of HCC. Both GYS1 and GYS2 were identified as promising biomarkers associated with diagnosis, prognosis and immune infiltration in HCC.

The association between vitamin C intake and breast cancer is unclear. This meta-analysis aimed to precisely assess the association of vitamin C intake with breast cancer risk and mortality. We searched the PubMed, Embase, and Web of Science databases up to June 2020 and found 69 studies relevant to breast cancer risk (54 studies) and survival (15 studies). Relative risks and 95% confidence intervals were calculated using the random-effects models. Pooled results suggested that the highest versus lowest vitamin C intake was significantly associated with a lower risk of breast cancer incidence (Relative Risk = 0.86; 95% confidence interval, 0.81-0.92). Dietary vitamin C but not supplements was found to reduce breast cancer risk (Relative Risk = 0.89; 95% confidence interval, 0.82-0.96). For the highest versus lowest vitamin C intake, the pooled hazard risk for breast cancer-specific mortality was 0.78 (95% confidence interval, 0.69-0.88), totality mortality was 0.82 (95% confidence interval, 0.74-0.91), and recurrence was 0.81 (95% confidence interval, 0.67-0.99). Our analysis suggests that higher vitamin C intake is significantly associated with reduced breast cancer incidence and mortality. However, the intake of vitamin C supplements has no significant effect on breast cancer prevention.

BackgroundThe treatment for locally advanced breast cancer (LABC) is a severe clinical problem. The postoperative radiotherapy is a conventional treatment method for patients with LABC, whereas the effect of preoperative radiotherapy on outcome of LABC remains controversial. This study aimed to examine and compare the overall survival (OS) in patients with LABC who underwent preoperative radiotherapy or postoperative radiotherapy.MethodsThis retrospective cohort study included 41,618 patients with LABC from the National Cancer Database (NCDB) between 2010 and 2014. We collected patients’ demographic, clinicopathologic, treatment and survival information. Propensity score was used to match patients underwent pre-operative radiotherapy with those who underwent post-operative radiotherapy. Cox proportional hazard regression model was performed to access the association between variables and OS. Log-rank test was conducted to evaluate the difference in OS between groups.ResultsThe estimated median follow-up of all included participants was 69.6 months (IQR: 42.84-60.22); 70.1 months (IQR: 46.85-79.97) for postoperative radiotherapy, 68.5 (IQR: 41.13-78.23) for preoperative radiotherapy, and 67.5 (IQR: 25.92-70.99) for no radiotherapy. The 5-year survival rate was 80.01% (79.56-80.47) for LABC patients who received postoperative radiotherapy, 64.08% (57.55-71.34) for preoperative radiotherapy, and 59.67% (58.60-60.77) for no radiotherapy. Compared with no radiation, patients receiving postoperative radiotherapy had a 38% lower risk of mortality (HR=0.62, 95%CI: 0.60-0.65, pConclusionsPatients with LABC underwent postoperative radiotherapy had improved overall survival, whereas no significant survival benefit was observed in patients receiving preoperative radiotherapy. Preoperative radiotherapy did not present a better survival than postoperative radiotherapy for LABC patients.

Cancer is the leading cause of death among children.We report on the latest estimates of the burden of cancer among children at the global, regional, and national levels from 1990 to 2019.Based on the Global Burden of Disease Study 2019, children's cancer data were analyzed by sex, age, year, and location. Age-standardized rates were used to compare the burdens among regions and nations. Joinpoint analysis was applied to assess the temporal trend of the global childhood cancer burden.In 2019, 291,319 (95% uncertainty interval [UI], 254,239 to 331,993) new cases and 98,834 (86,124 to 113,581) deaths from childhood cancer were documented globally. Further, 8,302,464 (7,230,447 to 9,555,118) DALYs and 1,806,630 (1,567,808 to 2,089,668) prevalent cases were recorded in the same year. Age-standardized incidence and prevalence rates of childhood cancer were greatest in higher SDI settings and increased most significantly in Australasia and Southern Latin America over the last 30 years. However, although age-standardized death and DALY rates of childhood cancer have remarkably decreased in all regions since 1990, countries with a lower SDI showed the highest rates in 2019, particularly in countries in Eastern Sub-Saharan Africa. Among all cancers, leukemia has shown the largest decrease in burden since 1990. Despite this, leukemia was still the most common cancer and the leading cause of death among children in 2019, followed by brain and central nervous system cancer.On a global scale, the childhood cancer burden has significantly fallen over the last 30 years, but is still higher in lower SDI countries. Effective interventions and collaborations among nations should be facilitated to improve healthcare among children with cancer in countries with lower SDI.

Background Liver cancer has caused a serious disease burden worldwide wherein prognostic risk factors may have had a significant role. However, previous studies have focused on liver cancer distributions and trend variations without analyzing the role of risk factors. Methods We assessed liver cancer burden attributable to five recognized risk factors as well as temporal trends from 1990 to 2019 based on the 2019 Global Burden of Disease Study. The risk exposure levels and their contributed burden were estimated by cause, sex, age, and location. Furthermore, the relationship between the risks and social-demographic index (SDI) was investigated. Results The total liver cancer burden attributable to risk factors is still increasing year by year in terms of death and disability-adjusted life years. However, the burden attributable to alcohol use and smoking has shown a downward trend in recent years. Risk-related burden in males was more than three times as that in females, the burden among the middle-aged and elderly was the most serious, and Central Asia, high-income Asia Pacific and East Asia exhibited the highest burden worldwide. The exposure levels of the five recognized risk factors were generally positively correlated with SDI value. However, the risk-related liver cancer burden first increased and then decreased with the SDI value. Conclusion These findings could help in understanding the role of prognostic risk factors in liver cancer burden, in promoting the development of relevant studies, and in proposing better prevention and control policies tailored to local conditions.

Triple-negative breast cancer is a special type of breast cancer, characterized by younger onset age, shorter survival period, higher malignant degree, higher mortality, recurrence and metastasis. Triple-negative breast cancer is more harmful to women's life and health, compared with other types of breast cancer. This paper mainly studied the role of miR-585 in triple-negative breast cancer. Real-time quantitative PCR was used to detect the expression of miR-585 in triple-negative breast cancer cell lines and tissues. Kaplan-Meier curve and Cox proportional hazards model analysis were used to investigate the prognostic value of miR-585 in triple-negative breast cancer. CCK-8 and Transwell assays were used to detect cell proliferation, invasion and migration. miR-585 was significantly down-regulated in triple-negative breast cancer cells and tissues. The low expression of miR-585 has been shown to be significantly associated with poor prognosis in triple-negative breast cancer patients. Abnormally low expression of miR-585 can promote cell proliferation, migration and invasion. Overall, abnormally low expression of miR-585 is associated with prognosis and progression of triple-negative breast cancer. miR-585 may serve as a prognostic biomarker for patients with triple-negative breast cancer and it is expected to be a new method and strategy for the treatment of triple-negative breast cancer.

Background Ovarian cancer (OV) is deemed the most lethal gynecological cancer in women. The aim of this study was to construct an effective gene prognostic model for predicting overall survival (OS) in patients with OV. Methods The expression profiles of glycolysis‐related genes (GRGs) and clinical data of patients with OV were extracted from The Cancer Genome Atlas (TCGA) database. Univariate, multivariate, and least absolute shrinkage and selection operator Cox regression analyses were conducted, and a prognostic signature based on GRGs was constructed. The predictive ability of the signature was analyzed using training and test sets. Results A gene risk signature based on nine GRGs (ISG20, CITED2, PYGB, IRS2, ANGPTL4, TGFBI, LHX9, PC, and DDIT4) was identified to predict the survival outcome of patients with OV. The signature showed a good prognostic ability for OV, particularly high‐grade OV, in the TCGA dataset, with areas under the curve (AUC) of 0.709 and 0.762 for 3‐ and 5‐year survival, respectively. Similar results were found in the test sets, and the AUCs of 3‐, 5‐year OS were 0.714 and 0.772 in the combined test set. And our signature was an independent prognostic factor. Moreover, a nomogram combining the prediction model and clinical factors was developed. Conclusion Our study established a nine‐GRG risk model and nomogram to better predict OS in patients with OV. The risk model represents a promising and independent prognostic predictor for patients with OV. Moreover, our study on GRGs could offer guidance for the elucidation of underlying mechanisms in future studies., Novel 9‐gene risk signature based on glycolysis‐related genes was developed to predict ovarian cancer survival. A nomogram combining the gene signature and patient characteristics provided superior estimation of overall survival. Our research provided a new prognostic tool and guidelines for future research.

Background: Prognosis classifier is necessary for patients with hepatocellular carcinoma (HCC). Here, we developed a clinically applicable automatic system to predict prognosis directly from HCC histology image. Methods: In total, 1480 participants were enrolled (ZJU1: n=202, ZJU2: n=179, ZJU3: n=738, TCGA: n=361). We trained 7 convolutional neural network (CNN) nets to select the top one in learning HCC image. Firstly, lesion detector and lesion decomposer net (classifying lesion into five different classes) were developed in ZJU1 and validated in ZJU2. Second, a prognosis classifier using the classes derived from decomposer net was constructed by LASSO Cox in ZJU3. Lastly, the two nets and the prognosis classifier were validated in external TCGA. Findings: Of the 7 CNNs, VGG19 achieved the top performer for detecting lesion with an accuracy of 96.4%, and classifying lesion with test accuracy of 99% in ZJU2. In ZJU3, two classes derived from the decomposer net were significantly associated with RFS (p

Key Points Question Can a better prognosis model based on DNA repair–related genes be developed for the comprehensive evaluation of breast cancer? Findings In this prognostic study based on samples from 1096 women, a novel signature for breast cancer constructed using 8 DNA repair–related genes showed satisfactory performance for predicting survival in the training cohort from The Cancer Genome Atlas and the validation cohort from the Gene Expression Omnibus database. The DNA repair–related gene signature was an independent predictor of survival after adjustment for clinical characteristics. Meaning A prognostic signature based on 8 DNA repair–related genes predicted overall survival among female patients with breast cancer, thereby providing a new modality for the accurate diagnosis and targeted treatment of breast cancer., Importance Breast cancer (BC), a common malignant tumor, ranks first among cancers in terms of morbidity and mortality among female patients. Currently, identifying effective prognostic models has a significant association with the prediction of the overall survival of patients with BC and guidance of clinicians in early diagnosis and treatment. Objectives To identify a potential DNA repair–related prognostic signature through a comprehensive evaluation and to further improve the accuracy of prediction of the overall survival of patients with BC. Design, Setting, and Participants In this prognostic study, conducted from October 9, 2019, to February 3, 2020, the gene expression profiles and clinical data of patients with BC were collected from The Cancer Genome Atlas database. This study consisted of a training set from The Cancer Genome Atlas database and 2 validation cohorts from the Gene Expression Omnibus, which included 1096 patients with BC. A prognostic signature based on 8 DNA repair–related genes (DRGs) was developed to predict overall survival among female patients with BC. Main Outcomes and Measures Primary screening prognostic biomarkers were analyzed using univariate Cox proportional hazards regression analysis and the least absolute shrinkage and selection operator Cox proportional hazards regression. A risk model was completely established through multivariate Cox proportional hazards regression analysis. Finally, a prognostic nomogram, combining the DRG signature and clinical characteristics of patients, was constructed. To examine the potential mechanisms of the DRGs, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. Results In this prognostic study based on samples from 1096 women with BC (mean [SD] age, 59.6 [13.1] years), 8 DRGs (MDC1, RPA3, MED17, DDB2, SFPQ, XRCC4, CYP19A1, and PARP3) were identified as prognostic biomarkers. The time-dependent receiver operating characteristic curve analysis suggested that the 8-gene signature had a good predictive accuracy. In the training cohort, the areas under the curve were 0.708 for 3-year survival and 0.704 for 5-year survival. In the validation cohort, the areas under the curve were 0.717 for 3-year survival and 0.772 for 5-year survival in the GSE9893 data set and 0.691 for 3-year survival and 0.718 for 5-year survival in the GSE42568 data set. This DRG signature mainly involved some regulation pathways of vascular endothelial cell proliferation. Conclusions and Relevance In this study, a prognostic signature using 8 DRGs was developed that successfully predicted overall survival among female patients with BC. This risk model provides new clinical evidence for the diagnostic accuracy and targeted treatment of BC., This prognostic study evaluates a potential DNA repair–related prognostic signature to improve the accuracy of prediction of the overall survival of patients with breast cancer.

Rationale: Dysregulation of the PI3K/AKT/mTOR pathway occurs frequently in cancers, providing an attractive therapeutic target for anticancer treatments. DEPTOR plays essential roles in regulation of cell proliferation and survival by directly modulating mTOR activity. However, whether DEPTOR regulates the growth of ErbB2-positive breast cancer cells remains unknown. Methods: DEPTOR expression was determined by TCGA data analysis and immunohistochemistry of human breast tissue microarrays. The membrane localization of DEPTOR was demonstrated by immunofluorescence and subcellular fractionation. The interaction of DEPTOR with ErbB2 was determined by immunoprecipitation. Furthermore, the biological significance of this interaction was assessed by ATPlite cell growth, clonogenic survival, and flow cytometry-based apoptosis assays. Results: DEPTOR promoted the proliferation and survival of ErbB2-positive breast cancer cells by directly interacting with and stabilizing ErbB2. Specifically, DEPTOR translocates to cell membrane and interacts with ErbB2 to disrupt ErbB2 polyubiquitination and degradation promoted by β-TrCP, an E3 ubiquitin ligase. DEPTOR knockdown destabilizes ErbB2 by shortening its protein half-life to inactivate ErbB2-PI3K-AKT-mTOR signaling, leading to the suppression of cell proliferation and survival by inducing apoptosis. Ectopic expression of a constitutively active ErbB2 mutant completely rescued the reduction in cell proliferation and survival by DEPTOR knockdown. Importantly, DEPTOR expression is increased in human breast cancer tissues and its overexpression correlates with poor patient survival. Moreover, DEPTOR is located on the cell membrane in ErbB2-positive breast cancer tissues, but not in tumor-adjacent normal tissues, indicating that DEPTOR may contribute to the oncogenic characteristics of ErbB2. Conclusions: Our study reveals a novel mechanism by which DEPTOR promotes breast cancer cell proliferation and survival by stabilizing ErbB2.

Background Liver transplantation is an effective therapy for end‐stage liver diseases and acute liver failure. After the operation, however, recipients may suffer grafts loss induced by alloimmune reaction, which is termed as acute allograft rejection. The interaction between costimulatory molecules, CD276, and its ligand, TREML2, promotes T cell‐mediated immune response, as well as acute or chronic allograft rejection. Our research aimed at correlating genetic polymorphisms of CD276/TREML2 with acute rejection, and evaluating its prognostic value of acute rejection after liver transplantation. Methods The study enrolled a total of 388 recipients. Among them, acute allograft rejection was observed in 54 cases. We performed single nucleotide polymorphism genotyping of CD276, including rs11072431, rs11574495, rs12593558, rs12594627, rs2127015, rs3816661 and rs7176654, and TREML2, including rs4714431, rs6915083, rs7754593, and rs9394767 from preoperative peripheral blood genome DNA. Results We found rs2127015 of CD276, rs6915083 and rs7754593 of TREML2, and HBV infection as well were associated with acute rejection. And, rs2127015 influences CD276 expression. Moreover, we established a risk assessment model, composited by statistically proved risk factors. Conclusion By integrating both clinical and genetic variables, liver transplant recipients can be categorized into different risk groups, and might benefit from individualized therapies.

Summary The transcriptional regulators YAP and TAZ play important roles in development, physiology, and tumorigenesis and are negatively controlled by the Hippo pathway. It is yet unknown why the YAP/ TAZ proteins are frequently activated in human malignancies in which the Hippo pathway is still active. Here, by a gain-of-function cancer metastasis screen, we discovered OTUB2 as a cancer stemness and metastasis-promoting factor that deubiquitinates and activates YAP/TAZ. We found OTUB2 to be poly-SUMOylated on lysine 233, and this SUMOylation enables it to bind YAP/TAZ. We also identified a yet-unknown SUMO-interacting motif (SIM) in YAP and TAZ required for their association with SUMOylated OTUB2. Importantly, EGF and oncogenic KRAS induce OTUB2 poly-SUMOylation and thereby activate YAP/TAZ. Our results establish OTUB2 as an essential modulator of YAP/TAZ and also reveal a novel mechanism via which YAP/TAZ activity is induced by oncogenic KRAS.

Table S6. Correlation of PHF8 expression with expression of ATG17/ FIP200 and E-cadherin based on immunohistochemistry analysis. (DOCX 14 kb)

Figure S3. The blockage of PHF8 inhibits tumorigenesis and metastasis in vivo. a – d) Appearance of primary tumor, tumor growth curves and tumor weight in two groups (n = 6). d Overview of lung metastatic lesions (upper panel, white arrow indicated the metastatic colonization) and HE images (lower panel, magnification, × 100). e The number of lung metastatic nets of each group was counted in a low power field (n = 6). * P

Table S3. Oligonucleotide sequences of primers for ChIP. (DOCX 16 kb)

Table S2. Details of primary antibodies. (DOCX 15 kb)

Table S5. Univariate- and Multivariate- analysis of risk factors for relapse-free survival (RFS) and overall survival (OS). (DOCX 18 kb)

Table S4. Association of PHF8 expression with clinicopathologic features. (DOCX 17 kb)

Table S1. Oligonucleotide sequences of primers for quantitative real time PCR. (DOCX 13 kb)

Although the involvement of insulin-like signaling in cancer has been well documented in various types of cancers, the association between the genetic variants in the insulin-like signaling and the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unclear. In this study, a total of 498 individuals including 173 HBV related cirrhosis patients, 171 HBV-related HCC patients, and 154 healthy controls were enrolled. Sixteen single nucleotide polymorphisms (SNPs) in IGF1, IGF2, IGF1R and IGF2R have been genotyped by employing SNaPshot assays. We found A/A genotype at rs3743251 of IGF1R was negatively associated with HBV related HCC [odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.20-0.72, P = 0.037]; A/G genotype decreased the risk of portal vein thrombosis (OR = 0.38, 95%CI = 0.18-0.82, P = 0.01). These results indicate that rs3743251 polymorphism in IGF1R is associated with the susceptibility of HBV-related HCC.

Plant homeodomain finger protein 8 (PHF8) serves an activator of epithelial-mesenchymal transition (EMT) and is implicated in various tumors. However, little is known about PHF8 roles in hepatocellular carcinoma (HCC) and regulating E-cadherin expression. PHF8 expression pattern was investigated by informatic analysis and verified by RT-qPCR and immunochemistry in HCC tissues and cell lines. CCK8, xenograft tumor model, transwell assay, and tandem mCherry-GFP-LC3 fusion protein assay were utilized to assess the effects of PHF8 on proliferation, metastasis and autophagy of HCC cells in vitro and in vivo. ChIP, immunoblot analysis, rescue experiments and inhibitor treatment were used to clarify the mechanism by which PHF8 facilitated EMT, metastasis and autophagy. PHF8 upregulation was quite prevalent in HCC tissues and closely correlated with worse overall survival and disease-relapse free survival. Furthermore, PHF8-knockdown dramatically suppressed cell growth, migration, invasion and autophagy, and the expression of SNAI1, VIM, N-cadherin and FIP200, and increased E-cadherin level, while PHF8-overexpression led to the opposite results. Additionally, FIP200 augmentation reversed the inhibited effects of PHF8-siliencing on tumor migration, invasion and autophagy. Mechanistically, PHF8 was involved in transcriptionally regulating the expression of SNAI1, VIM and FIP200, rather than N-cadherin and E-cadherin. Noticeably, E-cadherin degradation could be accelerated by PHF8-mediated FIP200-dependent autophagy, a crucial pathway complementary to transcriptional repression of E-cadherin by SNAI1 activation. These findings suggested that PHF8 played an oncogenic role in facilitating FIP200-dependent autophagic degradation of E-cadherin, EMT and metastasis in HCC. PHF8 might be a promising target for prevention, treatment and prognostic prediction of HCC.

Objective Acute rejection resulting from alloimmune responses is a major risk factor affecting patient survival following liver transplantation. Since interleukin (IL)-6 can mediate acute rejection, the association between IL-6 gene single nucleotide polymorphisms (SNPs) and incidence of acute rejection in liver transplant recipients was investigated. Methods Patients who received liver transplant between January 2005 and December 2010 were typed for IL6-572C/G (rs1800796) polymorphisms using the snapshot technique. Association between genotype and acute rejection was analysed using the SNP Statistics website: http://bioinfo.iconcologia.net/snpstats/start.htm . Allelic and genotypic distributions for rs1800796 were compared among 335 patients with or without acute rejection within the first 6 months following liver transplant. Results Incidence of acute rejection was 11.94%. A heterozygous CG genotype for IL6-572C/G was associated with a lower acute rejection rate compared with homozygous CC or GG genotypes. Conclusion IL6-572 CG genotype may be related to protection from acute rejection following liver transplant in Han Chinese patients.

Background Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains one of the most common causes of poor long-term survival. However, the host genetic factors affecting increased risk of tumor recurrence after transplantation have not been thoroughly elucidated. The present study was designed to investigate the association of cytokine gene polymorphisms with the risk of tumor recurrence in LT patients for HCC. Methods Eleven single-nucleotide polymorphisms within the promoter regions of 7 cytokine genes, i.e., the IL-1 family (IL-Iα and IL-Iβ), IL-6, IL-8, IL-10, TNF-α, and TGF-βI, were genotyped in 93 HCC patients treated with LT using DNA sequencing. The association between these polymorphisms and the risk of tumor recurrence was evaluated while controlling confounding clinical variables. Results The genotype frequency of IL-10 −1082 A/G in patients with and without recurrence of HCC was AA 83.3%, GA 16.7% and AA 97.6%, GA 2.4%, respectively. The association between IL-10 −1082 GA and recurrence was significant ( P =0.033). No other single-nucleotide polymorphism in the cytokine gene was found to be associated with recurrence. Kaplan-Meier survival curves showed that the homozygous AA patients had a significantly longer mean recurrence-free survival than heterozygous GA patients (23.5 vs 5.7 months, P =0.001). However, multivariate analysis failed to reveal that the GA genotype of IL-10 −1082 A/G was an independent indicator of recurrence. Conclusions This study suggests the lack of association of selected cytokine gene polymorphisms with HCC recurrence after LT in the Han Chinese population. The finding does not exclude the idea that other cytokine polymorphisms could act as candidate biomarkers of disease prognosis.