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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Semin+Oncol
2014 ; 41
(3
): 406-414
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Identification of two clinical hepatocellular carcinoma patient phenotypes from
results of standard screening parameters
#MMPMID25023357
Carr BI
; Pancoska P
; Giannini EG
; Farinati F
; Ciccarese F
; Rapaccini GL
; Marco MD
; Benvegnų L
; Zoli M
; Borzio F
; Caturelli E
; Chiaramonte M
; Trevisani F
Semin Oncol
2014[Jun]; 41
(3
): 406-414
PMID25023357
show ga
Previous work has shown that two general processes contribute to hepatocellular
cancer (HCC) prognosis: liver damage, monitored by indices such as blood
bilirubin, prothrombin time (PT), and aspartate aminostransferase (AST); and
tumor biology, monitored by indices such as tumor size, tumor number, presence of
portal vein thrombosis (PVT) and blood alpha-fetoprotein (AFP) levels. These
processes may affect one another, with prognostically significant interactions
between multiple tumor and host parameters. These interactions form a context
that provide personalization of the prognostic meaning of these factors for every
patient. Thus, a given level of bilirubin or tumor diameter might have a
different significance in different personal contexts. We previously applied
network phenotyping strategy (NPS) to characterize interactions between liver
function indices of Asian HCC patients and recognized two clinical phenotypes, S
and L, differing in tumor size and tumor nodule numbers. Our aim was to validate
the applicability of the NPS-based HCC S/L classification on an independent
European HCC cohort, for which survival information was additionally available.
Four sets of peripheral blood parameters, including AFP-platelets, derived from
routine blood parameter levels and tumor indices from the ITA.LI.CA database,
were analyzed using NPS, a graph-theory-based approach that compares personal
patterns of complete relationships between clinical data values to reference
patterns with significant association to disease outcomes. Without reference to
the actual tumor sizes, patients were classified by NPS into two subgroups with S
and L phenotypes. These two phenotypes were recognized using solely the HCC
screening test results, consisting of eight common blood parameters, paired by
their significant correlations, including an AFP-platelets relationship. These
trends were combined with patient age, gender, and self-reported alcoholism into
NPS personal patient profiles. We subsequently validated (using actual scan data)
that patients in L phenotype group had 1.5× larger mean tumor masses relative to
S, P = 6 × 10(-16). Importantly, with the new data, liver test pattern-identified
S-phenotype patients had typically 1.7× longer survival compared to L-phenotype
patients. NPS integrated the liver, tumor, and basic demographic factors.
Cirrhosis-associated thrombocytopenia was typical for smaller S tumors. In L
tumor phenotype, typical platelet levels increased with the tumor mass. Hepatic
inflammation and tumor factors contributed to more aggressive L tumors, with
parenchymal destruction and shorter survival. NPS provides integrative
interpretation for HCC behavior, identifying two tumor and survival phenotypes by
clinical parameter patterns. The NPS classifier is provided as an Excel tool. The
NPS system shows the importance of considering each tumor marker and parameter in
the total context of all the other parameters of an individual patient.