Molecular characteristics of hepatocellular carcinomas from different age groups.

Celina Ang,Carol Farhangfar,Joanne Xiu,Anthony Shields,Igor Astsaturov,Jimmy Hwang,Mohamed E Salem,Zoran Gatalica,Sandeep Reddy,John L Marshall

doi:10.18632/oncotarget.21353

Abstract

While most patients in Western countries who are diagnosed with HCC are in their 50s and 60s, HCCs diagnosed at extremes of the age spectrum (i.e., < 40 years and ≥ 75 years) are less common and have been linked with distinct geographic locations and etiologies. Using multiplatform profiling, we identified differences in genetic alterations and protein expression in different age groups within a large cohort of HCC patients (N = 421). Young adult HCC patients (18-39 years’ old) were more likely to be female, living in the West and Midwestern United States, and showed decreased androgen receptor, drug resistance and pro-angiogenic protein expression compared to older patients. TP53 mutations were the most frequent alteration in young adults (19%), whereas CTNNB1 mutations occurred in 30-33% of patients ≥ 40 years’ old. The overall frequency of pathogenic and presumed pathogenic mutations was observed to increase significantly with advancing age. To our knowledge, these data represent one of the only studies to analyze age-specific molecular profiles in HCC, and provide a basis for further exploration and validation of these findings with respect to their clinical and therapeutic implications.

Highlights

Hepatocellular carcinoma (HCC) is an aggressive malignancy, representing the second and sixth leading cause of cancer deaths worldwide in men and women, respectively [1]
The majority of HCC patients in the Western hemisphere are diagnosed in their 50s and 60s, though HCCs diagnosed at extremes of the age spectrum (i.e., < 40 years, ≥ 75 years) occur
A total of 421 specimens were included in this dataset: 39 (9%) were from young adults (18-39 years’ old), 46 (11%) from elderly patients (≥ 75 years’ old) and 336 (80%) from the intermediate age group (40-74 years’ old)

Summary

Introduction

Hepatocellular carcinoma (HCC) is an aggressive malignancy, representing the second and sixth leading cause of cancer deaths worldwide in men and women, respectively [1]. HCC typically arises in the context of chronic liver disease and cirrhosis due to viral hepatitis, excessive alcohol consumption, fatty liver disease and other risk factors. The majority of HCC patients in the Western hemisphere are diagnosed in their 50s and 60s, though HCCs diagnosed at extremes of the age spectrum (i.e., < 40 years, ≥ 75 years) occur. The highest incidence of HCC in individuals ≥ 75 years' old, in men, has been reported in low-risk Western countries, South Africa and Egypt where hepatitis C prevails [2]; whereas young adult patients (i.e., 20-40 years’ old) diagnosed with HCC primarily reside in hepatitis B endemic regions. Over 85% of patients ≤ 40 years of age were found to be hepatitis B surface antigen seropositive compared to 60%

Methods

Results

Conclusion