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Page 6 of 9 Martini et al. Hepatoma Res 2018;4:28 I http://dx.doi.org/10.20517/2394-5079.2018.50

SCCA-IgM above the cut-off (200 AU/mL) developed more frequently HCC during follow-up than those
[54]
negative for the biomarker .

Patients with HCC
In a recent study that has retrospectively analyzed patients with cirrhosis and HCC, SCCA-IgM was proven
efficient in the prediction of HCC prognosis, identifying HCC patients with long overall and progression-free
[55]
survival . Median survival was indeed about two fold increased in patients with low levels of SCCA-IgM,
compared to those with elevated SCCA-IgM levels. At multivariate analysis tumour size and SCCA-IgM
levels were identified as the only independent predictors of survival. In addition, levels of this biomarker
were correlated with overall response to treatment, with a median time to progression that was more than
doubled in patients with low SCCA-IgM levels . The levels of the biomarker at four weeks were stable
[55]
or increased in treated patients with stable disease or tumor, and were reduced in patients with complete
response, while patients with partial response showed an intermediate behaviour. It is worth to note that
in the same study, AFP was not able to predict complete response . Another recent study addressed the
[55]
behaviour of SCCA-IgM in patients with HCC who underwent locoregional therapy. Among the enrolled
patients with a new diagnosis of HCC, SCCA-IgM levels at basal time and after one month of treatment,
[56]
resulted significantly lower in patients who responded to therapy compared to those who did not respond .
These findings need to be confirmed in further studies, but are supported by a previous report that within
the liver, HCCs with high SCCA-1 tissue expression have a poor prognosis and present higher rate of early
recurrence after surgical resection .
[8]

FUTURE PERSPECTIVES
Chronic inflammation and immune system play a crucial role in the development of dysplastic nodules
and liver cancer [41,44] , as the pathogenesis of HCC has been associated with hepatocyte death, infiltration of
inflammatory cells, and compensatory liver regeneration, which is dependent on the production of hepatic
mitogenic cytokines produced by Kuppfer cells, such as IL-6 . A previous study documented a positive
[57]
correlation between RAS mutation, enhanced SerpinB3 and interleukin-6 expression in samples of human
colorectal and pancreatic tumors, reflecting an inflammatory response related to the nuclear factor kappa-
light chain enhancer of activated B cell . Moreover, SerpinB3 was found physiologically expressed on
[58]
the surface of CD27+ B lymphocytes , and it has been detected in peripheral blood mononuclear cells at
[59]
transcript level both in cultured and in primary monocytes . These findings suggest that SerpinB3 might
[60]
play a role in the modulation of the immune response, favouring tumor development, but further studies are
needed to clearly elucidate its role in this specific field.

DECLARATIONS
Authors’ contributions
Drafted the article: Martini A
Revised the article and approved the version to be published: Pontisso P

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
Both authors declare that there are no conflicts of interest.