Gene expression in hepatocellular carcinoma: pilot study of potential transarterial chemoembolization response biomarkers.
OBJECTIVE
To perform a feasibility study to explore the relationship between hepatocellular carcinoma genetics and transarterial chemoembolization treatment response to identify potential biomarkers associated with enhanced treatment efficacy.


METHODS
In this single-institution study, pretreatment hepatocellular carcinoma biopsy specimens for tumors in 19 patients (14 men, five women; mean age, 59 y) treated with chemoembolization between 2007 and 2013 were analyzed for a panel of 60 chemotherapy-sensitivity, hypoxia, mitosis, and inflammatory genes with the QuantiGene Plex 2.0 mRNA detection assay. Demographic, disease, and procedure data and tumor response outcomes were collected. Quantitative mRNA levels were compared based on radiologic response between tumors exhibiting complete response (CR) versus partial response (PR).


RESULTS
The study sample included 19 biopsy specimens from tumors (mean size, 3.0 cm; grade 1, n = 6; grade 2, n = 9; grade 3, n = 4) in patients treated with a mean of two conventional chemoembolization sessions. Thirteen and six tumors exhibited CR and PR, respectively, at a mean of 116 days after treatment. Tumors with CR showed a significant increase in (P < .05) or trend toward (P < .1) greater (range, 1.49-3.50 fold) pretreatment chemotherapy-sensitivity and mitosis (ATF4, BAX, CCNE1, KIF11, NFX1, PPP3CA, SNX1, TOP2A, and TOP2B) gene mRNA expression compared with tumors with PR, in addition to lower CXCL10 levels (0.48-fold), and had significantly (P < .05) higher (1.65-fold) baseline VEGFA levels.


CONCLUSIONS
Genetic signatures may allow prechemoembolization stratification of tumor response probability, and gene analysis may therefore offer an opportunity to personalize locoregional therapy by enhancing treatment modality allocation. Further corroboration of identified markers and exploration of their respective predictive capacity thresholds is necessary.
Department of Radiology and Division of Interventional Radiology, University of Illinois Hospital and Health Sciences System, 1740 W. Taylor St., MC 931, Chicago IL 60612. Electronic address: rgaba@uic.edu.
Ron C
RC
Gaba
Department of Pathology, University of Illinois Hospital and Health Sciences System, 1740 W. Taylor St., MC 931, Chicago IL 60612.
John V
JV
Groth
Department of Radiology and Division of Interventional Radiology, University of Illinois Hospital and Health Sciences System, 1740 W. Taylor St., MC 931, Chicago IL 60612.
Ahmad
A
Parvinian
Department of Pathology, University of Illinois Hospital and Health Sciences System, 1740 W. Taylor St., MC 931, Chicago IL 60612.
Grace
G
Guzman
Department of Radiology and Division of Interventional Radiology, University of Illinois Hospital and Health Sciences System, 1740 W. Taylor St., MC 931, Chicago IL 60612.
Leigh C
LC
Casadaban
D015415:Biomarkers / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016133:Polymerase Chain Reaction
D015415:Biomarkers