Oxidative stress pathways in noncancerous human liver tissue to predict hepatocellular carcinoma recurrence: A prospective, multicenter study
✍ Scribed by Shinji Tanaka; Kaoru Mogushi; Mahmut Yasen; Daisuke Ban; Norio Noguchi; Takumi Irie; Atsushi Kudo; Noriaki Nakamura; Hiroshi Tanaka; Masakazu Yamamoto; Norihiro Kokudo; Tadatoshi Takayama; Seiji Kawasaki; Michiie Sakamoto; Shigeki Arii
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 623 KB
- Volume
- 54
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
The prediction of cancer recurrence holds the key to improvement of the postoperative prognosis of patients. In this study, the recurrence of early-stage hepatocellular carcinoma (HCC) after curative hepatectomy was analyzed by the genome-wide gene-expression profiling on cancer tissue and the noncancerous liver tissue. Using the training set of 78 cases, the cytochrome P450 1A2 (CYP1A2) gene in noncancerous liver tissue was identified as the predictive candidate for postoperative recurrence (hazard ratio [HR], 0.447; 95% confidence interval [CI], 0.249-0.808; P 5 0.010). Multivariate analysis revealed the statistically significant advantage of CYP1A2 down-regulation to predict recurrence (odds ratio, 0.534; 95% CI, 0.276-0.916; P 5 0.036), and the expression of CYP1A2 protein was confirmed immunohistochemically. An independently multi-institutional cohort of 211 patients, using tissue microarrays, validated that loss of expression of CYP1A2 in noncancerous liver tissue as the only predictive factor of recurrence after curative hepatectomy for early-stage HCC (HR, 0.480; 95% CI, 0.256-0.902; P 5 0.038). Gene set-enrichment analysis revealed close association of CYP1A2 down-regulation with oxidative stress pathways in liver tissue (P < 0.001, false discovery rate [FDR] 5 0.042; P 5 0.006, FDR 5 0.035). Our results indicate these pathways as the molecular targets to prevent recurrence, as well as the potential prediction of the super high-risk population of HCC using liver tissue. (HEPATOLOGY 2011;54:1273-1281) H epatocellular carcinoma (HCC) is one of the most common malignancies, accounting for nearly 700,000 deaths per year, and the incidence is still increasing worldwide. 1 A major obstacle in treatment is the high frequency of tumor recurrence that is mostly limited to liver tissue, even after curative resection. 2 There have been a number of studies reporting that advanced tumor factors, including size, number, and vascular invasion of cancer, were significantly associated with HCC recurrence. 3 Genome-wide geneexpression analysis by DNA microarray offers a systematic approach to unfold comprehensive information