Prediction of early-stage hepatocellular carcinoma using Onco Scan chromosomal copy number aberration data

AIM To identify chromosomal copy number aberrations(CNAs) in early-stage hepatocellular carcinoma(HCC) and analyze whether they are correlated with patient prognosis.METHODS One hundred and twenty patients with early-stage HCC were enrolled in our study, with the collection of formalin fixed, paraffin-embedded(FFPE) specimens and clinicopathological data. Tumor areas were marked by certified pathologists on a hematoxylin and eosinstained slide, and cancer and adjacent non-cancerous tissues underwent extraction of DNA, which was analyzed with the Affymetrix Onco Scan platform to assess CNAs and loss of heterozygosity(LOH). Ten individuals with nonmalignant disease were used as the control group. Another cohort consisting of 40 patients with stage Ⅰ/Ⅱ HCC were enrolled to analyze gene expression and to correlate findings with the Onco Scan data.RESULTS Copy number amplifications occurred at chromosomes 1 q21.1-q44 and 8 q12.3-24.3 and deletions were found at 4 q13.1-q35.2, 8 p 23.2-21.1, 16 q23.3-24.3, and 17 p13.3-12, while LOH commonly occurred at 1 p32.3, 3 p21.31, 8 p23.2-21.1, 16 q22.1-24.3, and 17 p 13.3-11 in early-stage HCC. Using Cox regression analysis, we also found that a higher percentage of genome change(≥ 60%) was an independent factor for worse prognosis in early-stage HCC(P = 0.031). Among the 875 genes in the Onco Scan Gene Chip, six were independent predictors of worse disease-free survival, of which three were amplified(MYC, ELAC2, and SYK) and three were deleted(GAK, MECOM, and WRN). Further, patients with HCC who exhibited ≥ 3 CNAs involving these six genes have worse outcomes compared to those who had < 3 CNAs(P < 0.001). Similarly, Asian patients with stage I HCC from The Cancer Genome Atlas harboring CNAs with these genes were also predicted to have poorer outcomes.CONCLUSION Patients with early-stage HCC and increased genome change or CNAs involving MYC, ELAC2, SYK, GAK, MECOM, or WRN are at risk for poorer outcome after resection.

Liver resection for hepatocellular carcinoma larger than 10 cm: A multi-institution long-term observational study

BACKGROUND The treatment of hepatocellular carcinoma(HCC)≥10 cm remains a challenge.AIM To consolidate the role of surgical resection for HCC larger than 10 cm.METHODS Eligible HCC patients were identified from the Chang Gung Research Database,the largest multi-institution database,which collected medical records of all patients from Chang Gung Memorial Foundation.The surgical outcome of HCC≥10 cm(L-HCC)was compared to that of HCC<10 cm(S-HCC)(model 1).The survival of L-HCC after either liver resection or transarterial chemoembolization(TACE)was also analyzed(model 2).The long-term risks of all-cause mortality and recurrence were assessed to consolidate the role of surgery for L-HCC.RESULTS From January 2004 to July 2015,a total of 32403 HCC patients were identified from the Chang Gung Research Database.Among 3985 patients who received liver resection,3559(89.3%)had S-HCC,and 426 had L-HCC.The L-HCC patients had a worse disease-free survival(0.27 for L-HCC vs 0.40 for S-HCC)and overall survival(0.18 for L-HCC vs 0.45 for S-HCC)than the S-HCC after liver resection(both P<0.001).However,the surgical and long-term outcome of resected L-HCC had improved dramatically in the recent decades.After adjusting for covariates,surgery could provide a better outcome for L-HCC than TACE(adjusted hazard ratio of all-cause mortality:0.46,95%confidence interval:0.38-0.56 for surgery).Subgroup analysis stratified by different stages showed similar trend of survival benefit among L-HCC patients receiving surgery.CONCLUSION Our study demonstrated an improving surgical outcome for HCC larger than 10 cm.Under selected conditions,surgery is better than TACE in terms of disease control and survival and should be performed.Due to inferior survival,a subclassification within T1 stage should be considered.Future studies are mandatory to confirm our findings.

Attenuation of liver stiffness in sorafenib-treated patients with advanced hepatocellular carcinoma

Aim: Sorafenib is a multi-tyrosine kinase inhibitor and the standard therapy for advanced hepatocellular carcinoma (HCC). This retrospective study aimed to observe the anti-fibrotic effect of sorafenib in patients with advanced HCC. Methods: Seventeen patients with advanced HCC were recruited. Shear wave velocity (SWV) using acoustic radiation force impulse elastography and non-invasive serum markers for liver fibrosis, such as the aspartate aminotransferase (AST) to alanine aminotransferase ratio (AAR), the AST to platelet ratio index, the fibrosis-4 index and the Lok index, were recorded at the beginning of sorafenib treatment and 3-6 months after sorafenib treatment in 2014-2015. Results: Nine (52.9%) patients achieved disease control status and 8 had progressive disease after a mean duration of 11.1 months with sorafenib treatment. The mean SWV decreased from 2.37 m/s at the beginning to 1.90 m/s after sorafenib treatment (P < 0.01). This trend was observed in patients with and without liver cirrhosis (from 2.49 to 2.06 m/s, P = 0.06, and from 2.32 to 1.69 m/s, P < 0.05, respectively). Among the non-invasive serum markers, no statistically significant differences were observed except for the AAR in the cirrhotic group. Conclusion: Sorafenib has potential antif-ibrotic effects in patients with advanced HCC.