Leukocyte telomere length predicts overall survival in hepatocellular carcinoma treated with transarterial chemoembolization.

Previous studies have reported that telomere length in peripheral blood leukocytes can predict the clinical outcome of several cancers. However, whether leukocyte telomere length is associated with the prognosis of hepatocellular carcinoma (HCC) remains to be determined. In this study, relative telomere length (RTL) in peripheral blood leukocytes was measured using a real-time PCR-based method for 269 HCC patients treated with transarterial chemoembolization (TACE) from two independent hospitals. The association between RTL and the overall survival (OS) of HCC was analyzed. The immunological function of the HCC patients with different leukocyte RTLs was evaluated. Multivariate analyses indicated that long leukocyte RTL was significantly associated with poor OS of HCC patients, with a hazard ratio of 2.04 (95% confidence interval, 1.46-2.86; P < 0.001). Kaplan-Meier analyses showed a significant difference of median survival time between patients with long and short RTL (log rank P < 0.001). Fluorescence-activated cell sorting analyses showed that the long RTL group had a significantly increased percentage of CD4(+)CD25(+)FOXP3(+) Treg in CD4(+) T cells compared with short RTL group (P = 0.002). In conclusion, our results suggest that leukocyte RTL may serve as an independent prognostic marker for HCC patients treated with TACE.

Promoter hypomethylation up-regulates CD147 expression through increasing Sp1 binding and associates with poor prognosis in human hepatocellular carcinoma.

CD147 is a transmembrane glycoprotein overexpressed in human hepatocellular carcinoma (HCC) which could promote HCC progression and metastasis. Promoter methylation is one of the most important processes in gene regulation. In this study, we aim to investigate CD147 promoter methylation status and the correlation with clinicopathological features and prognosis in HCC. CD147 promoter methylation statuses and expression levels in normal and HCC cell lines and 54 paired HCC and adjacent non-tumour (ANT) tissues were, respectively, examined by bisulphite genomic sequencing, methylation-specific PCR, real-time RT-PCR, Western blot and immunohistochemistry. The correlations of promoter methylation statuses with CD147 expression level and the clinicopathological features were statistically analysed in HCC patients. Significantly higher expression of CD147 and significantly lower promoter methylation level were observed in HCC cell lines compared to normal cell lines and tissues control. In vivo and in vitro analysis indicated that demethylation with 5-Aza-2'-deoxycytidine led to increased CD147 expression through enhancing Sp1 binding affinity, and methylation with methyltransferase reduced CD147 transcriptional activity through interfering Sp1 binding. CD147 promoter methylation level in HCC tissues (22.22%) was lower than that in ANT tissues (46.30%; P < 0.05). Within HCC tissues, a significant inverse correlation was observed between CD147 expression and methylation level (r=-0.615). Moreover, HCC patients with unmethylated CD147 promoter had a significantly higher recurrence rate (88.1%versus 58.3%; P < 0.05) and death rate (83.3%versus 50.0%; P < 0.05) than patients with methylated CD147 promoter. In conclusions, promoter hypomethylation up-regulates CD147 expression primarily through increasing Sp1 binding and associates with poor prognosis in HCC patients.

Fatty acid synthesis pathway genetic variants and clinical outcome of non-small cell lung cancer patients after surgery.

Over-expression of de novo lipogenesis (DNL) genes is associated with the prognosis of various types of cancers. However, the effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and survival of non-small cell lung cancer (NSCLC) patients after surgery are still unknown. In this study, a total of 500 NSCLC patients who underwent surgery treatment were included. Eight SNPs in 3 genes (ACACA, FASN and ACLY) of the DNL pathway were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards regression and Kaplan-Meier curves were used to analyze the association of SNPs with patient survival and tumour recurrence. We found that two SNPs in the FASN gene were significantly associated with the recurrence of NSCLC. SNP rs4246444 had a significant association with lung cancer recurrence under additive model (hazard ratio [HR], 0.82; 95% confidence interval [95%CI], 0.67-1.00; p=0.05). Under the dominant model, rs4485435 exhibited a significant association with recurrence (HR, 0.75; 95%CI, 0.56-1.01; p=0.05). Additionally, SNP rs9912300 in ACLY gene was significantly associated with overall survival in lung cancer patients (HR, 1.41; 95%CI, 1.02-1.94, p=0.04) under the dominant model. Further cumulative effect analysis showed moderate dose-dependent effects of unfavorable SNPs on both survival and recurrence. Our data suggest that the SNPs in DNL genes may serve as independent prognostic markers for NSCLC patients after surgery.