Accelerating Decreases in the Incidences of Hepatocellular Carcinoma at a Younger Age in Shanghai Are Associated With Hepatitis B Virus Vaccination.

BackgroundRoutine vaccination of infants for protecting against hepatitis B virus (HBV) infection and its serious consequences, including hepatocellular cancer (HCC), has been carried out in Shanghai, China, since 1986. We therefore have examined the trend of HBV infection and HCC incidences before and after HBV vaccination over decades to assess the potential influences of the Shanghai HBV vaccination program.MethodsData on incidences of HBV infection and HCC were collected from the Shanghai Cancer Registry and the Shanghai HBV vaccination follow-up study. Joint-point regression and the Bayesian age-period-cohort statistical analysis methods were used.ResultsThe incidences of HBV infection dramatically declined from 23.09 and 1.13 per 100,000 for males and females in 2000 to 3.24 (-85.97%) and 0.22 (-80.53%) per 100,000 in 2014, respectively. Sero-epidemiological data from the sampling surveys during 20 years of follow-up showed that less than 1% of people undergoing HBV vaccination have a positive serum HBsAg. Consistently, the annual adjusted standardization rates (ASR) of HCC steadily fell from 33.38 and 11.65 per 100,000 for males and females in 1973 to 17.34 (-49.2%) and 5.60 (-51.9%) per 100,000 in 2014, respectively. The annual percentage change in overall HCC incidences is about -2%. HCC incidences in males at younger age groups (age <50 years old), particularly in those with age <34 groups, showed an accelerating decrease over time, whereas HCC incidences significantly declined in the female population across all age groups except for those under 19 years of age. The results supported that the universal HBV vaccination in newborns is easy to implement with high coverages and is effective for preventing both HBV infection and HCC in populations

DataSheet_1_Accelerating Decreases in the Incidences of Hepatocellular Carcinoma at a Younger Age in Shanghai Are Associated With Hepatitis B Virus Vaccination.docx

BackgroundRoutine vaccination of infants for protecting against hepatitis B virus (HBV) infection and its serious consequences, including hepatocellular cancer (HCC), has been carried out in Shanghai, China, since 1986. We therefore have examined the trend of HBV infection and HCC incidences before and after HBV vaccination over decades to assess the potential influences of the Shanghai HBV vaccination program.MethodsData on incidences of HBV infection and HCC were collected from the Shanghai Cancer Registry and the Shanghai HBV vaccination follow-up study. Joint-point regression and the Bayesian age-period-cohort statistical analysis methods were used.ResultsThe incidences of HBV infection dramatically declined from 23.09 and 1.13 per 100,000 for males and females in 2000 to 3.24 (-85.97%) and 0.22 (-80.53%) per 100,000 in 2014, respectively. Sero-epidemiological data from the sampling surveys during 20 years of follow-up showed that less than 1% of people undergoing HBV vaccination have a positive serum HBsAg. Consistently, the annual adjusted standardization rates (ASR) of HCC steadily fell from 33.38 and 11.65 per 100,000 for males and females in 1973 to 17.34 (-49.2%) and 5.60 (-51.9%) per 100,000 in 2014, respectively. The annual percentage change in overall HCC incidences is about -2%. HCC incidences in males at younger age groups (age <50 years old), particularly in those with age <34 groups, showed an accelerating decrease over time, whereas HCC incidences significantly declined in the female population across all age groups except for those under 19 years of age. The results supported that the universal HBV vaccination in newborns is easy to implement with high coverages and is effective for preventing both HBV infection and HCC in populations.</p

CDC25A^Q110del: A Novel Cell Division Cycle 25A Isoform Aberrantly Expressed in Non-Small Cell Lung Cancer

<div><h3>Objective</h3><p>Lung cancer remains number one cause of cancer related deaths worldwide. Cell cycle deregulation plays a major role in the pathogenesis of Non-Small Cell Lung Cancer (NSCLC). CDC25A represents a critical cell cycle regulator that enhances cell cycle progression. In this study we aimed to investigate the role of a novel CDC25A transcriptional variant, CDC25A^Q110del, on the regulation of the CDC25A protein, and its impact on prognosis of NSCLC patients.</p> <h3>Methodology/Principal Findings</h3><p>Here we report a novel CDC25A transcript variant with codon 110 (Glutamine) deletion, that we termed CDC25A^Q110del in NSCLC cells. In 9 (75%) of the 12 NSCLC cell lines, CDC25A^Q110del expression accounted for more than 20% of the CDC25A transcripts. Biological effects of CDC25A^Q110del were investigated in H1299 and HEK-293F cells using UV radiation, flowcytometry, cyclohexamide treatment, and confocal microscopy. Compared to CDC25A^wt, CDC25A^Q110del protein had longer half-life; cells expressing CDC25A^Q110del were more resistant to UV irradiation and showed more mitotic activity. Taqman-PCR was used to quantify CDC25A^Q110del expression levels in 88 primary NSCLC tumor/normal tissue pairs. In patients with NSCLC, Kaplan Meier curves showed tumors expressing higher levels of CDC25A^Q110del relative to the adjacent lung tissues to have significantly inferior overall survival (<em>P</em> = .0018).</p> <h3>Significance</h3><p>Here we identified CDC25A^Q110del as a novel transcriptional variant of CDC25A in NSCLC. The sequence-specific nature of the abnormality could be a prognostic indicator in NSCLC patients as well as a candidate target for future therapeutic strategies.</p> </div

Clinical Significance of CDC25A^Q110del.

<p>A. Kaplan Meier survival curves showed CDC25A^Q110del in tumor tissue to correlate with poor overall survival of NSCLC patients (log rank <i>P</i> = .074). B. Kaplan Meier Survival curves showed that when CDC25A^wt is higher in tumor versus normal tissue pair, it correlated with better overall survival (log rank <i>P</i> = .0018). Relative Quantification of target gene “CDC25A^wt” in NSCLC tumor tissue relative to normal tissue pair of NSCLC patients according to the formula: 2^−ΔΔct. CDC25A template of tumor or normal was run in triplicates of uniplex reaction for each of the Ct_wt and Ct_tot assays, and the mean was calculated for each assay.</p