23 research outputs found
NF-Y activates genes of metabolic pathways altered in cancer cells
The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Specific cancer-driving nodes are generally under NF-Y control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production and other anabolic pathways commonly altered in cancer cells
Years of life that could be saved from prevention of hepatocellular carcinoma
BACKGROUND:
Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved.
AIM:
To assess how many years of life are lost after HCC diagnosis.
METHODS:
Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables.
RESULTS:
Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth.
CONCLUSIONS:
Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost
Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype
Cirrhosis-related abnormal liver function is associated with predisposition to hepatocellular carcinoma (HCC). It features in several HCC classification systems and is an HCC prognostic factor. The aim of the present study was to examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. A 2,416-patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely, blood alpha-fetoprotein (AFP) levels, tumor size, presence of portal vein thrombosis (PVT) and tumor multifocality. In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality, and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even among patients with small tumors. A multiple logistic regression model for PVT or tumor multifocality showed increased odds ratios for elevated levels of gamma glutamyl transpeptidase (GGTP), bilirubin, and AFP and for larger tumor sizes. We conclude that HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had an increased incidence of PVT and tumor multifocality, and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness
Low alpha-fetoprotein HCC and the role of GGTP
BACKGROUND: HCC patients are heterogeneous in terms of both tumor and liver
factors. Alpha-fetoprotein (AFP) is an important prognostic tumor marker for
those patients with elevated AFP levels.
AIMS: To examine the differences in HCC patients with high or low AFP levels in
blood and evaluate the prognostic parameters in low AFP patients.
METHODS: A cohort of 2,440 HCC patients from 11 Italian medical centers was
studied. AFP-positive patients were compared to AFP-negative ones, and the blood
and tumor parameters of AFP-negative patients were examined.
RESULTS: Low blood AFP levels were found in 58% of the total cohort, in 64% of
patients with small HCCs, and in 51% of patients with large HCCs. In patients
with large tumors, platelet and gamma glutamyl transpeptidase (GGTP) levels,
tumor multifocality and portal vein thrombosis (PVT) incidence were all greater
than in patients with small tumors, regardless of AFP status. Patients with
higher AFP levels had worse survival rates than those with low AFP in each tumor
size group. In patients with small tumors, the elevated AFP was associated with
significantly increased PVT and worse survival. In patients with large tumors,
the elevated AFP was associated with significantly higher GGTP, ALKP, and
bilirubin levels, as well as with increased PVT and multifocality, and worse
survival. Low-AFP patients with high GGTP levels had worse survival than patients
with low GGTP levels.
CONCLUSION: Patients with low AFP were the majority in this cohort, and patients
with elevated GGTP had worse prognosis than those with low GGTP. GGTP may be a
useful tumor and prognosis marker in low-AFP patients. AFP-negative patients are
important to identify due to their enhanced survival
Hepatocellular carcinoma in patients without cirrhosis in Italy
BACKGROUND: In the Western world, hepatocellular carcinoma seldom develops in patients without cirrhosis, and reports describing the characteristics of non-cirrhotic patients with hepatocellular carcinoma are rather infrequent.
METHODS: We evaluated the main clinical characteristics, treatment options, and survival of patients with hepatocellular carcinoma developed in non-cirrhotic liver among the 3027 consecutive cases of hepatocellular carcinoma accrued in the Italian Liver Cancer database during the last 20 years.
RESULTS: We identified 52 patients with hepatocellular carcinoma in non-cirrhotic livers (1.7% of all hepatocellular carcinomas), 42 with (80.8%) and 10 without (19.2%) chronic liver disease. In patients without chronic liver disease, median tumour diameter was greater compared to patients with chronic liver disease (7.8 versus 4.0 cm, P=0.046). Curative treatment was feasible in 20 patients (38.5%). Median overall survival was 26 months and 5-year survival rate was 23.7%. Detection of hepatocellular carcinoma outside surveillance (P=0.036), advanced hepatocellular carcinoma stage (P<0.0001), and non-curative treatment (P=0.007) were associated with worse prognosis, but tumour stage was the only independent predictor of survival.
CONCLUSIONS: In Italy, less than 2% of hepatocellular carcinomas develop in a non-cirrhotic liver, and almost never in a normal liver. These patients frequently present with advanced tumours, have low eligibility rates for curative treatment, and have a dismal prognosis despite their preserved liver function
Significance of platelet and AFP levels and liver function parameters for HCC size and survival
BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous disease with both
tumor and liver factors being involved.
AIMS: To investigate HCC clinical phenotypes and factors related to HCC size.
METHODS: Prospectively-collected HCC patients' data from a large Italian database
were arranged according to the maximum tumor diameter (MTD) and divided into
tumor size terciles, which were then compared in terms of several common clinical
parameters and patients' survival.
RESULTS: An higer MTD tercile was significantly associated with increased blood
alpha-fetoprotein (AFP), gamma-glutamyl transpeptidase (GGTP), and platelet
levels. Patients with higher platelet levels had larger tumors and higher GGTP
levels, with lower bilirubin levels. However, patients with the highest AFP
levels had larger tumors and higher bilirubin levels, reflecting an aggressive
biology. AFP correlation analysis revealed the existence of 2 different groups of
patients: those with higher and with lower AFP levels, each with different
patient and tumor characteristics. The Cox proportional-hazard model showed that
a higher risk of death was correlated with GGTP and bilirubin levels, tumor size
and number, and portal vein thrombosis (PVT), but not with AFP or platelet
levels.
CONCLUSIONS: An increased tumor size was associated with increased blood platelet
counts, AFP and GGTP levels. Platelet and AFP levels were important indicators of
tumor size, but not of survival
Alpha-fetoprotein has no prognostic role in small hepatocellular carcinoma identified during surveillance in compensated cirrhosis.
none14Alpha-fetoprotein is a tumor marker that has been used for surveillance and diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. The prognostic capability of this marker in patients with HCC has not been clearly defined. In this study our aim was to evaluate the prognostic usefulness of serum alpha-fetoprotein in patients with well-compensated cirrhosis, optimal performance status, and small HCC identified during periodic surveillance ultrasound who were treated with curative intent. Among the 3,027 patients included in the Italian Liver Cancer study group database, we selected 205 Child-Pugh class A and Eastern Cooperative Group Performance Status 0 patients with cirrhosis with a single HCC ≤ 3 cm of diameter diagnosed during surveillance who were treated with curative intent (hepatic resection, liver transplantation, percutaneous ethanol injection, radiofrequency thermal ablation). Patients were subdivided according to alpha-fetoprotein serum levels (i.e., normal ≤ 20 ng/mL; mildly elevated 21-200 ng/mL; markedly elevated >200 ng/mL). Patient survival, as assessed by the Kaplan-Meier method, was not significantly different among the three alpha-fetoprotein classes (P = 0.493). The same result was obtained in the subgroup of patients with a single HCC ≤ 2 cm (P = 0.714). An alpha-fetoprotein serum level of 100 ng/mL identified by receiver operating characteristic curve had inadequate accuracy (area under the curve = 0.536, 95% confidence interval = 0.465-0.606) to discriminate between survivors and deceased patients.
CONCLUSION:
Alpha-fetoprotein serum levels have no prognostic meaning in well-compensated cirrhosis patients with single, small HCC treated with curative intent.Giannini, Eg; Marenco, S; Borgonovo, G; Savarino, V; Farinati, F; Del Poggio, P; Rapaccini, Gl; Di Nolfo, Ma; Benvegnù, L; Zoli, M; Borzio, F; Caturelli, E; Chiaramonte, M; Trevisani, F.Giannini, EDOARDO GIOVANNI; Marenco, Simona; Borgonovo, Giacomo; Savarino, Vincenzo; Farinati, F; Del Poggio, P; Rapaccini, Gl; Di Nolfo, Ma; Benvegnù, L; Zoli, M; Borzio, F; Caturelli, E; Chiaramonte, M; Trevisani, F