Molecular characteristics of hepatocellular carcinomas (HCC) from different age groups

Background

HCC patients (pts) from the Western hemisphere are usually diagnosed in their 50s and 60s, whereas HCCs in young adults (YA, 18-39 years) and the elderly (E, >75 years) are less common. Worldwide, HCCs diagnosed at extremes of the age spectrum are associated with distinct geography and etiologies. Multiplatform profiling data were used to compare molecular characteristics of HCCs of different age groups.

Methods

Gene sequencing, amplification and protein expression data on 421 HCC specimens were reviewed and stratified into YA, E and intermediate age (IA, 40-74 years) subgroups. Only pathogenic or presumed pathogenic (P/PP) mutations were analyzed. The Chi-square test was used for statistical comparisons. Etiologies are being collected.

Results

There were 39 YA, 336 IA and 46 E pts. Female prevalence was higher in YAs (54%) vs IA (23%, p  0.05). MRP1 expression decreased in YAs (60%) vs IA (86%, p = 0.04) and E pts (95%, p = 0.02). MGMT was higher in IA than YA (71% vs. 49%, p = 0.007) and SPARC higher in E than YA (13% vs.0, p = 0.005). PDGFR and PD-L1 were expressed in IA (14% and 10%) and E pts (29% and 17%) but not YAs. Of 47 genes analyzed, TP53 was the most frequent alteration in YAs (19%) while CTNNB1 was the most frequent in E (33%) and IA (30%) and only 9.5% in YA . PIK3CA, PTEN, and PTPN11 mutations were more prevalent in E (13.3%, 7.1% and 6.7%, respectively) vs IA pts (1.4%, 0.7% and 0%, all p 

Conclusions

HCCs from YAs were associated with female sex, decreased drug resistance protein and AR expression. YAs may be more sensitive to alkylating agents whereas E pts may be more sensitive to PIK3CA/Akt/mTOR or MAPK pathway inhibitors. Our results provide important knowledge to prospective studies among a network of cancer centers that will also incorporate etiological factors and molecular features into investigations for HCC therapies.

Clinical trial identification

Legal entity responsible for the study

Celina Ang

Funding

N/A

Disclosure

J. Xiu, Z. Gatalica, S. Reddy: Employee of Caris Life Sciences. All other authors have declared no conflicts of interest.