Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations.

Background Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Methods Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Results Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. Conclusions The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance

The evolution of sex-specific virulence in infectious diseases

Fatality rates of infectious diseases are often higher in men than women. Although this difference is often attributed to a stronger immune response in women, we show that differences in the transmission routes that the sexes provide can result in evolution favouring pathogens with sex-specific virulence. Because women can transmit pathogens during pregnancy, birth or breast-feeding, pathogens adapt, evolving lower virulence in women. This can resolve the long-standing puzzle on progression from Human T-cell Lymphotropic Virus Type 1 (HTLV-1) infection to lethal Adult T-cell Leukaemia (ATL); a progression that is more likely in Japanese men than women, while it is equally likely in Caribbean women and men. We argue that breastfeeding, being more prolonged in Japan than in the Caribbean, may have driven the difference in virulence between the two populations. Our finding signifies the importance of investigating the differences in genetic expression profile of pathogens in males and females

Prevalence of human T-lymphotropic virus type 1 and 2 among blood donors in Manaus, Amazonas State, Brazil

Introduction: Human T-lymphotropic virus type 1 and 2 (HTLV-1/2) is endemic in Brazil, but few studies have investigated the seroprevalence of HTLV and its subtypes among blood donors in the capital city Manaus, Amazonas State, Brazil. Aim: To estimate the seroprevalence of HTLV-1/2 and to identify circulating subtypes among blood donors in Manaus. Materials and Methods: Blood donors (2001-2003) were screened for HTLV-1/2 antibodies by ELISA. Positive results were confirmed and subtyped by Western blot assays. Prevalence rates were calculated and compared with demographic data. Results: Among the 87,402 individuals screened, 116 (0.13%) were seropositive for HTLV-1/2. A second sample (76/116) was collected and retested by HTLV-1/2 ELISA, of which only 41/76 were positive. Western blot confirmed HTLV infection in 24/41 retested blood donors [HTLV-1 (n=16), HTLV-2 (n=5) and HTLV-untypable (n=3)]. Discussion: HTLV-1 and HTLV-2 are prevalent among blood donors in Manaus. However, additional studies are needed to comprehend the epidemiology of HTLV-1/2 in Amazonas not only to understand the pathophysiology of the disease providing adequate medical assistance, but also to reduce or block virus transmission. © 2017, Instituto de Medicina Tropical de Sao Paulo. All rights reserved

Diet and hepatocellular carcinoma: A case-control study in Greece

We conducted a case-control study in Athens, Greece, to investigate the role of diet in the etiology of hepatocellular carcinoma (HCC). Subjects were 97 incident cases of HCC and 128 controls with no history of cancer admitted for minor ailments In three major hospitals. Information on diet was collected using a validated food frequency questionnaire and infection with hepatitis virus B (HBV) or C (HCV) was assessed using third-generation assays. Data were modeled through multiple logistic regression. We found no evidence that vegetable intake may reduce the risk of HCC, as reported in earlier investigations. In a multivariate model, only consumption of milk and dairy products appear-ed to be inversely related to HCC risk (odds ratio = 0.70, 95% confidence interval = 0.49-1.01), but the association was not statistically significant and is likely to have been generated by the multiple comparisons undertaken overall. Our data do not support an association of specific food groups or particular nutrients with the risk of HCC, whether positive or negative for HBV and/or HCV

Birth order, as a proxy for age at infection, in the etiology of hepatocellular carcinoma

First-born and second-born children are exposed to common infections after enrollment at school, whereas later-born children are exposed to these infections earlier through their older siblings. We have evaluated whether birth order is a risk factor for hepatitis B virus (HBV)-related, hepatitis C virus (HCV)related, and apparently virus-unrelated hepatocellular carcinoma (HCC) in a large case-control study that included 333 HCC cases and 632 controls. In comparison with controls who were carriers of hepatitis B surface antigen (HBsAg), HBsAg-positive HCC cases were more likely to have been later-born children (odds ratio per increase in birth order = 2.0; 95% confidence interval = 1.2-3.6). There was no such evidence for anti-HCV-positive cases compared with anti-HCV-positive controls or for virus-negative HCC cases compared with virus-negative controls. We conclude that early infection with HBV increases the risk of HBV carriers to develop HCC, over and beyond its role in facilitating the establishment of a carrier state

Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma

During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of hepatocellular carcinoma (HCC), as well as from 360 controls who were hospitalized for eye, ear, nose, throat or orthopedic conditions in Athens, Greece. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays, and information on smoking habits and beverage consumption was obtained. We found a significant dose-response, positive association between smoking and HCC risk [greater than or equal to 2 packs per day, odds ratio (OR) = 2.5]. This association was stronger in individuals without chronic infection with either HBV or HCV (greater than or equal to 2 packs per day, OR = 2.8). Consumption of alcoholic beverages above a threshold of 40 glasses per week increased the risk of HCC (OR = 1.9). We also found evidence of a strong, statistically significant and apparently super-multiplicative effect of heavy smoking and heavy drinking in the development of HCC (OR for both exposures = 9.6). This interaction was particularly evident: among individuals without either HBsAg or anti-HCV (OR for both exposures = 10.9). Coffee intake was not positively associated with HCC risk, but the reverse could not be excluded for the subgroup of chronically infected individuals. In conclusion, tobacco smoking and heavy alcohol consumption are associated with increased risk of HCC, especially when these 2 exposures occur together. Int. J. Cancer 85:498-502, 2000. (C) 2000 Wiley-Liss, Inc