Abstract
Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC), a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SH-HCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP) were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs). The expression of α-smooth muscle actin (α-SMA), p21Waf1/Cif1, γ-H2AX, and IL-6 was investigated by immunohistochemistry or immunofluorescence. SH-HCCs were associated with older age, higher body mass index, and a higher incidence of metabolic syndrome, compared to C-HCC (P <0.05, all). The numbers of α-SMA-positive cancer-associated fibroblasts (CAFs) (P = 0.049) and α-SMA-positive CAFs co-expressing p21Waf1/Cif1 (P = 0.038), γ-H2AX (P = 0.065), and IL-6 (P = 0.048) were greater for SH-HCCs than C-HCCs. Additionally, non-tumoral liver from SH-HCCs showed a higher incidence of non-alcoholic fatty liver disease and a higher number of α-SMA-positive stellate cells expressing γ-H2AX and p21Waf1/Cif1 than that from C-HCCs (P <0.05, all). In conclusion, SH-HCCs are considered to occur more frequently in metabolic syndrome patients. Therein, senescent and damaged CAFs, as well as non-tumoral stellate cells, expressing SASP including IL-6 may contribute to the development of SH-HCC.
Highlights
As in Western countries, the prevalence of metabolic syndrome is rapidly increasing in Asia, including Korea [1, 2]
Diabetes, and hypertriglyceridemia were more frequently seen in Steatohepatitic hepatocellular carcinoma (SH-hepatocellular carcinoma (HCC)) patients than in conventional HCCs (C-HCCs) patients (P
Chronic hepatitis B virus (HBV) infection was present in 15 (71.4%) SH-HCCs and 29 (85.3%) C-HCCs, including occult HBV infection (4 cases in SH-HCCs and 5 cases in C-HCCs), and there was no significant difference between the two groups
Summary
We aimed to investigate alterations of the tumor stroma in SH-HCCs, comparing the expression of CAFs, HSCs, senescence-associated proteins, and SASP factors (p21Waf1/Cif, γ-H2AX, and IL-6) between SH-HCCs and C-HCCs
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have