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Abstract Background Aberrant alternative splicing (AS) contributes to tumor progression. A crucial component of AS is cleavage and polyadenylation specificity factor 4 (CPSF4). It remains unclear whether CPSF4 plays a role in triple-negative breast cancer (TNBC) progression through AS regulation. In this study, our objective is to investigate the prognostic value of CPSF4 and pinpoint pivotal AS events governed by CPSF4 specifically in TNBC. Methods We examined the expression levels and prognostic implications of CPSF4 in patients diagnosed with TNBC through public databases. CPSF4-interacting transcripts, global transcriptome, and alternative splicing were captured through RNA immunoprecipitation sequencing (RIP-seq) and RNA sequencing (RNA-seq). The top 10 CPSF4-regulated alternative splicing events (ASEs) were validated using qRT-PCR. TNBC cells transfected with high mobility group 20B (HMG20B) siRNA were subjected to CCK-8 and transwell assays. Results In TNBC, CPSF4 exhibited heightened expression levels and was correlated with unfavorable prognosis. Overexpression of CPSF4 significantly promoted colony formation and migration, whereas knockdown of CPSF4 had the opposite effect. Inhibition of CPSF4 altered the transcriptome profile of MDA-MB-231 cells. CPSF4-regulated numerous genes showed enrichment in cancer-related functional pathways, including mRNA processing, cell cycle, RNA transport, mRNA surveillance pathway, and apoptosis. CPSF4-regulated ASEs were highly validated by qRT-PCR. CPSF4 modulated selective splicing events by inhibiting alternative 3′ splice site events of HMG20B and promoted cell proliferation, migration, and invasion. Conclusion CPSF4 promotes TNBC progression by regulating AS of HMG20B. These findings contribute to the development of more useful prognostic, diagnostic and potentially therapeutic biomarkers for TNBC.

Abstract Breast cancer represents the most prevalent tumor type and a foremost cause of mortality among women globally. The complex pathophysiological processes of breast cancer tumorigenesis and progression are regulated by protein post-translational modifications (PTMs), which are triggered by different carcinogenic factors and signaling pathways, with small ubiquitin-like modifier (SUMOylation) emerging as a particularly pivotal player in this context. Recent studies have demonstrated that SUMOylation does not act alone, but interacts with other PTMs, such as phosphorylation, ubiquitination, acetylation, and methylation, thereby leading to the regulation of various pathological activities in breast cancer. This review explores novel and existing mechanisms of crosstalk between SUMOylation and other PTMs. Typically, SUMOylation is regulated by phosphorylation to exert feedback control, while also modulates subsequent ubiquitination, acetylation, or methylation. The crosstalk pairs in promoting or inhibiting breast cancer are protein-specific and site-specific. In mechanism, alterations in amino acid side chain charges, protein conformations, or the occupation of specific sites at specific domains or sites underlie the complex crosstalk. In summary, this review centers on elucidating the crosstalk between SUMOylation and other PTMs in breast cancer oncogenesis and progression and discuss the molecular mechanisms contributing to these interactions, offering insights into their potential applications in facilitating novel treatments for breast cancer.

Sorafenib resistance is a major obstacle influencing its therapeutic efficacy in advanced hepatocellular carcinoma (HCC). The knowledge of circular RNAs (circRNAs), a group of novel endogenous non-coding RNAs, in sorafenib resistance of HCC is still inadequate. In this study, a series of bioinformatic analyses and validation were performed. Firstly, a dataset GSE101850 was included for screening out differentially expressed circRNAs between sorafenib resistant and sensitive HCC, after which the structural patterns and binding microRNAs (miRNAs) of these candidate circRNAs were acquired. By combination of the results from expression, prognosis and diagnosis analysis, miR-221-3p and miR-222-3p were selected as the most potential binding miRNAs of hsa_circ_0006220, which was correlated with sorafenib resistance of HCC. Next, the target genes of miR-221-3p and miR-222-3p were predicted. Subsequently, ESR1 was identified as the top one hub gene among all these target genes. By conducting survival analysis and correlation analysis, ESR1 and KDR were considered as the most potential genes associated with sorafenib resistance of HCC. Collectively, we elucidated a potential hsa_circ_0006220-miR-221/222-3p-ESR1/KDR regulatory axis linked to sorafenib resistance of HCC.

Liver metastasis is the main lethal cause of colorectal cancer (CRC). The knowledge of role and mechanism of circular RNA (circRNA) in liver metastasis of CRC is still inadequate. In this study, whole-transcriptome analysis was performed using three datasets (GSE147597, GSE147602 and GSE147603). A total of 14 potential circRNAs were identified, after which their structural patterns and binding miRNAs were obtained. Next, 45 differentially expressed miRNAs (DEmiRNAs) between CRC without and with liver metastasis were acquired, consisting 38 upregulated and 7 downregulated miRNAs. After conducting intersection analysis, expression validation and correlation analysis, miR-761 and miR-424-5p were selected as the most potential miRNAs linked to liver metastasis of CRC. Subsequently, the target genes of miR-761 or miR-424-5p were predicted and differentially expressed genes (DEGs) between CRC without and with liver metastasis were obtained. 257 genes that were commonly appeared in predicted genes and DEGs were significantly enriched in “epithelial-to-mesenchymal transition” and “signaling by Robo receptor”. Among these enriched genes, only TPM2, SRPX and SRGAP1 were significantly negatively correlated with miR-424-5p and were positively linked to hsa_circ_0000375 in CRC without or with liver metastasis. Collectively, the current findings elucidated a potential hsa_circ_0000375-miR-424-5p-TPM2/SRPX/SRGAP1 network contributing to liver metastasis of CRC.

Introduction: Cancer is the leading cause of death among children. Objectives: We report on the latest estimates of the burden of cancer among children at the global, regional, and national levels from 1990 to 2019. Methods: 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. Results: 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. Conclusions: 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.

Abstract 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.

IntroductionThis study aimed to describe the latest epidemiology of female breast cancer globally, analyze the change pattern of the incidence rates and the disease’s association with age, period, and birth cohort, and subsequently present a forecast of breast cancer incidence.MethodsData for analysis were obtained from Global Burden of Disease (GBD) Study 2019 and World Population Prospects 2019 revision by the United Nations (UN). We described the age-standardized incidence rates (ASIRs) from 1990 to 2019 and then calculated the relative risks of period and cohort using an age-period-cohort model, and predicted the trends of ASIRs to 2035.ResultsIn 2019, the global incidence of breast cancer in women increased to 1,977,212 (95% uncertainty interval = 1 807 615 to 2 145 215), with an ASIR of 45.86 (41.91 to 49.76) per 100 000 person-year. Among the six selected countries facing burdensome ASIRs, only the USA showed a downward trend from 1990 to 2019, whereas the others showed an increasing or stable trend. The overall net drift was similar in Japan (1.78%), India (1.66%), and Russia (1.27%), reflecting increasing morbidity from 1990 to 2019. The increase in morbidity was particularly striking in China (2.60%) and not significant in Germany (0.42%). The ASIRs were predicted to continue to increase globally, from 45.26 in 2010 to 47.36 in 2035. In most countries and regions, the age specific incidence rate is the highest in those aged over 70 years and will increase in all age groups until 2035. In high-income regions, the age specific incidence rates are expected to decline in women aged over 50 years.ConclusionsThe global burden of female breast cancer is becoming more serious, especially in developing countries. Raising awareness of the risk factors and prevention strategies for female breast cancer is necessary to reduce future burden.

The expression of the SRY-Box Transcription Factor 15 (Sox15) is reduced by DNA methylation, and its progression is suppressed within numerous tumors. However, its effect on hepatocellular carcinoma (HCC) remains unknown. In the present work, the clinical importance and function of Sox15, as well as the underlying molecular mechanism, were explored within HCC. The expression of Sox15 is reduced and positively correlated with prognosis in HCC as analyzed by GEPIA (Gene Expression Profiling Interactive Analysis) and OncoLnc. Meanwhile, the hypermethylated Sox15 promoter CpG-site predicted a dismal HCC prognosis. Besides, ectopic Sox15 expression within the HCC cells (LM3, HUH7, SK-hep-1) remarkably inhibited in vitro cell growth and inhibited xenograft tumorigenesis in the nude mice. Moreover, Sox15 inactivated the Wnt pathway under both in vivo and in vitro conditions. To summarize, Sox15 played a tumor suppressor role within the HCC via the inactivated Wnt pathway. Sox15 and CpG-site methylation of its promoter are the factors that independently predict the prognosis of HCC.

Background: Antihypertensive drugs might play a key role in the risk and poor prognosis of colorectal cancer. However, current epidemiologic evidence remains inconsistent. The aim of this study is to quantify the association between antihypertensive drugs and colorectal cancer.Methods: To identify available studies, we systematically searched electronic databases: PubMed, Web of Science, Embase, Cochrane Library. The risk estimates and their corresponding 95% confidence intervals (CIs) were collected and analyzed by using random-effects models. Heterogeneity test and sensitivity analysis were also performed.Results: Overall, 37 observational studies were included in this analysis (26 studies with cohort design, three studies with nested case-control design, and 8 studies with case-control design). Antihypertensive drugs did not present a significant effect on the risk or overall survival of patients with colorectal cancer [Risk ratio (RR) = 1.00, 95% CI: 0.95–1.04; Hazard ratio (HR) = 0.93, 95% CI: 0.84–1.02]. In the subgroup analysis, diuretics use was significantly associated with a worse overall survival of patients with colorectal cancer (HR = 1.27; 95% CI: 1.14–1.40). However, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was associated with improved progression-free survival of patients who suffered from colorectal cancer (HR = 0.83; 95% CI: 0.72–0.95).Conclusion: Antihypertensive drug usage did not influence the risk and overall survival of patients with colorectal cancer in general. Further investigation reminded us that diuretics use might reduce the overall survival time in colorectal cancer patients, whereas those who took Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers had a longer progression-free survival.

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, p

Background: Colorectal cancer remains a public health problem worldwide. Dietary risk factors play a key role in the carcinogenesis and progression of colorectal cancer. This study aimed to explore the geographical and temporal trends in various dietary factor-related colorectal cancers.Methods: Data were extracted from the Global Burden of Disease (GBD) 2019 study, including the deaths, disability-adjusted life-years (DALYs), age-standardized rate (ASR), and summary exposure value (SEV) among 4 world regions, 11 age groups, 21 regions, and 204 countries and territories between 1990 and 2019. The estimated annual percentage changes (EAPCs) were calculated to evaluate the variation trend of ASR.Results: Dietary factors were the leading cause of colorectal cancer death and DALY rate, regardless of age. Dietary factor-related deaths and DALYs accounted for 32 and 34% of global colorectal cancer, respectively. Further analysis showed that low whole grain intake remained the leading cause of cancer death and DALY rate, followed by milk and calcium. Diets that were low in whole grains, milk, and calcium accounted for 81.61% of deaths and 81.64% of DALYs. Deaths and DALYs of dietary factors related to colorectal cancer grew by half from 1990 to 2019. All ASRs remained higher for men than women. Asia carried the highest colorectal cancer burden attributed to dietary risks, especially for East Asia [age-standardized death rate (ASDR): EAPC = 1.15, 95% CI:0.88–1.42; DALY: EAPC = 1.08, 95% CI:0.82–1.34]. The heavy burden also existed in high-middle and middle socio-demographic index (SDI) quintiles. China has always had the highest deaths and DALYs of colorectal cancer attributable to dietary risks, followed by the USA, India, and Japan.Conclusions: Large variations existed in the dietary risk-related colorectal cancer burdens among sexes, regions, and countries. More targeted interventions to address modifiable dietary risk factors would save 32% of deaths and 34% of DALYs for colorectal cancer.

To identify a glycolysis-related gene signature for the evaluation of prognosis in patients with breast cancer, we analyzed the data of a training set from TCGA database and four validation cohorts from the GEO and ICGC databases which included 1,632 patients with breast cancer. We conducted GSEA, univariate Cox regression, LASSO, and multiple Cox regression analysis. Finally, an 11-gene signature related to glycolysis for predicting survival in patients with breast cancer was developed. And Kaplan–Meier analysis and ROC analyses suggested that the signature showed a good prognostic ability for BC in the TCGA, ICGC, and GEO datasets. The analyses of univariate Cox regression and multivariate Cox regression revealed that it’s an important prognostic factor independent of multiple clinical features. Moreover, a prognostic nomogram, combining the gene signature and clinical characteristics of patients, was constructed. These findings provide insights into the identification of breast cancer patients with a poor prognosis.

Abstract Background 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. Methods 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. Results 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. Conclusion 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.

Abstract 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.

In the publication of our publication [1], we have noticed there is a wrong label in Fig. 1e, in which the position of “HCC” and “Adjacent” should be transposed.

In the publication of this article [1], there are two inadvertent errors.

BACKGROUND:Although liver transplantation is one of the most efficient curative therapies of end stage liver diseases, recipients may suffer liver graft loss opst-operation. IRF-5, a member of Interferon Regulatory Factors, functions as a key regulator in TLR4 cascade, and is capable of inducing inflammatory cytokines. Although TLR4 has been proved to contribute to acute allograft rejection, including after liver transplantation, the correlation between IRF5 gene and acute rejection has not been elucidated yet. METHODS:The study enrolled a total of 289 recipients, including 39 females and 250 males, and 39 recipients developed acute allograft rejection within 6 months post-transplantation. The allograft rejections were diagnosed by liver biopsies. Genome DNA of recipients was extracted from pre-operative peripheral blood. Genotyping of IRF-5, including rs3757385, rs752637 and rs11761199, was performed, followed by SNP frequency and Hardy-Weinberg equilibrium analysis. RESULTS:The genetic polymorphism of rs3757385 was found associated with acute rejection. G/G homozygous individuals were at higher risk of acute rejection, with a P value of 0.042 (OR = 2.34 (1.07-5.10)). CONCLUSIONS:IRF5, which transcriptionally activates inflammatory cytokines, is genetically associated with acute rejection and might function as a risk factor for acute rejection of liver transplantations.

BACKGROUND:This work seeks to evaluate the association between the C/D ratios (plasma concentration of tacrolimus divided by daily dose of tacrolimus per body weight) of tacrolimus and the haplotypes of MDR1 gene combined by C1236T (rs1128503), G2677A/T (rs2032582) and C3435T (rs1045642), and to further determine the functional significance of haplotypes in the clinical pharmacokinetics of oral tacrolimus in Han Chinese liver transplant recipients. METHODOLOGY/PRINCIPAL FINDINGS:The tacrolimus blood concentrations were continuously recorded for one month after initial administration, and the peripheral blood DNA from a total of 62 liver transplant recipients was extracted. Genotyping of C1236T, G2677A/T and C3435T was performed, and SNP frequency, Hardy-Weinberg equilibrium, linkage disequilibrium, haplotypes analysis and multiple testing were achieved by software PLINK. C/D ratios of different SNP groups or haplotype groups were compared, with a p value

Breast cancer (BC) is the most common female malignancy within the spectrum of human cancer. One promising way to reduce the mortality and morbidity of BC is to explore novel diagnostic markers for early diagnosis and prognostication. The neutrophil lymphocyte ratio (NLR) is a good reflection of inflammation, which plays an important role in tumor progression and metastasis. However, the association between NLR and BC prognosis remains unclear. The aim of this meta-analysis is to explore the prognostic value of NLR in BC. Among the screened references in the database, 12 eligible studies were identified in this study. Patients with a higher NLR had a shorter disease-free survival (hazard ratio =1.46, 95% confidence interval: 1.12-1.90, P=0.044) and overall survival (hazard ratio =2.03, 95% confidence interval: 1.41-2.93, P<0.001). In the subgroup analysis of NLR and disease-free survival, the studies from Eastern countries had a positive result with perfect homogeneity (I2=0); however, this homogeneity has not been achieved in studies from Western countries. In the subgroup analysis of the NLR and overall survival, the results of the univariate and multivariate analyses were completely different, with different heterogeneity. In the luminal A and luminal B subtypes, we found that there was no association between the NLR and overall survival in the BC patients. Positive results were obtained in the analyses of the human epidermal growth factor receptor 2 (HER2)-positive and triple-negative BC subtypes. In conclusion, this meta-analysis suggests that NLR is a good prognostic marker for BC, and patients with a higher NLR have poorer prognoses. Future studies should perform more detailed investigations to decrease heterogeneity and determine the appropriate cut-off values for different races. [ABSTRACT FROM AUTHOR]

Cancer-associated inflammation is a key determinant of disease progression and survival in most cancers. The aim of our study was to assess the predictive value of preoperative inflammatory markers, such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, red cell distribution width (RDW), and mean platelet volume, for survival in breast cancer patients. In total, 608 breast cancer patients operated on between January 2009 and December 2011 were included in this observational study. The association between preoperative inflammatory markers and survival outcomes was analyzed. Patients with high NLR (>2.57) or high RDW (>13.45%) showed a significantly lower overall survival rate than those with lower NLR (⩽2.57) or lower RDW (⩽13.45%). NLR and RDW, along with node stage and molecular subtypes, were independent prognostic factors. There was a significant survival difference according to NLR in the luminal A and triple-negative subtypes (93.3% versus 99.3%, P=0.001; 68.8% versus 95.1%, P=0.000, respectively). The triple-negative subtype was the only subtype in which higher RDW patients showed significantly poor prognosis (81.3% versus 95.5%, P=0.025). Pre-operation NLR and RDW is a convenient, easily measured prognostic indicator for patients with breast cancer, especially in patients with the triple-negative subtype. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence suggesting that interleukin-18 (IL-18) plays a crucial role in viral clearance and disease pathogenesis, and that single nucleotide polymorphisms (SNPs) within the gene may influence its production. Objectives: To investigate the potential association of two polymorphisms ( 137G/C and 607C/A) in the promoter region of the IL-18 gene with the risk of HBV recurrence after liver transplantation (LT) in Han Chinese patients. Patients and Methods: IL-18 promoter genotyping was performed by the snapshot technique in 125 patients with HBV-related end-stage liver disease (ESLD) receiving LT in our center from 2004 to 2008. Results: Among the study samples, no significant association between the IL-18 promoter polymorphisms ( 137G/C and 607C/A) or haplotypes and HBV recurrence after LT was found. Conclusions: The polymorphisms ( 137G/C and 607C/A) in the promoter region of the IL- 18 gene may not play a key role in HBV recurrence after LT in Han Chinese population, and may not be suitable predictors for HBV recurrence in clinical practice. [ABSTRACT FROM AUTHOR]