Abstract
We previously described a divergent clinical and molecular presentation of hepatocellular carcinoma (HCC) in Peru. The present study aimed to further characterize the tissue features associated with this singular nosological form of HCC in order to gain insight into the natural history of the disease. We performed an exploratory analysis of the histology of both tumor and non-tumor liver (NTL) tissues from 50 Peruvian HCC patients, and compared with that of 75 individuals with non-HCC liver tumor or benign liver lesions as a baseline for NTL features. We complemented this approach with a transcriptome analysis in a subset of NTL tissue samples and also performed an ultra-sensitive hepatitis B virus (HBV) detection in liver tissues of the patients. Overall, results highlighted the low rate of liver parenchymal alterations in a young patient cohort (median age: 40 years old), despite a strong prevalence of underlying HBV infection (c. 67%). Withal, liver clear cell foci of cellular alteration were genuinely associated with HCC and appended to some changes in immune and G protein-coupled receptor gene expression ontologies. Our findings confirm the occurrence of a particular setting of HCC in South America, a region where the pathophysiology of liver cancer remains largely unexplored.
Highlights
We previously described a peculiar clinical epidemiology of hepatocellular carcinoma (HCC) among patients attending the National Cancer Institute of Peru (INEN) in Lima, Peru[6]
We found that several genes, which are key players for carbohydrate anabolism, were transcriptionally overexpressed in periodic acid–Schiff (PAS)(+) non-tumor liver (NTL) compared to PAS(−) NTLs, such as insulin-like growth factor 1 (IGF1) (P = 6.17E-03), insulin receptor substrate 1 (IRS1) (P = 2.26E-02), forkhead box O1 (FOXO1) (P = 1.11E-02), or even pyruvate dehydrogenase kinase 4 (PDK4) (P = 1.73E-03)
HCC arising in non-cirrhotic liver displays several histopathological and clinical features that distinguish it from HCC occurring in the setting of cirrhosis[18]
Summary
We previously described a peculiar clinical epidemiology of HCC among patients attending the National Cancer Institute of Peru (INEN) in Lima, Peru[6] These HCC patients displayed notable clinical features: (i) 50% of them were relatively young with a median age below 40 years old; (ii) the large majority of the patients presented with advanced-stage HCC and large tumors exceeding 10 cm diameter; and last but not least, (iii) only 11% of HCCs occurred in the context of cirrhosis, whereas the proportion of cirrhotic patients with HCC in relevant literature ranges from 80% to 90%7–9. We contrasted this HCC patient population with a second cohort of Peruvian individuals with primary or secondary, non-HCC liver tumor or benign liver lesions as a baseline for NTL features in order to gain insight into the tissue alterations associated with the development of non-fibrolamellar HCC in young, non-cirrhotic individuals
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