Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
Key Laboratory of Medical Bioinformatics, Fujian Province, Fuzhou, China.
Liver Int. 2018 Oct;38(10):1812-1819. doi: 10.1111/liv.13864. Epub 2018 May 12.
BACKGROUND & AIMS: Currently, using biopsy specimens to confirm suspicious liver lesions of early hepatocellular carcinoma are not entirely reliable because of insufficient sampling amount and inaccurate sampling location. It is necessary to develop a signature to aid early hepatocellular carcinoma diagnosis using biopsy specimens even when the sampling location is inaccurate.
Based on the within-sample relative expression orderings of gene pairs, we identified a simple qualitative signature to distinguish both hepatocellular carcinoma and adjacent non-tumour tissues from cirrhosis tissues of non-hepatocellular carcinoma patients.
A signature consisting of 19 gene pairs was identified in the training data sets and validated in 2 large collections of samples from biopsy and surgical resection specimens. For biopsy specimens, 95.7% of 141 hepatocellular carcinoma tissues and all (100%) of 108 cirrhosis tissues of non-hepatocellular carcinoma patients were correctly classified. Especially, all (100%) of 60 hepatocellular carcinoma adjacent normal tissues and 77.5% of 80 hepatocellular carcinoma adjacent cirrhosis tissues were classified to hepatocellular carcinoma. For surgical resection specimens, 99.7% of 733 hepatocellular carcinoma specimens were correctly classified to hepatocellular carcinoma, while 96.1% of 254 hepatocellular carcinoma adjacent cirrhosis tissues and 95.9% of 538 hepatocellular carcinoma adjacent normal tissues were classified to hepatocellular carcinoma. In contrast, 17.0% of 47 cirrhosis from non-hepatocellular carcinoma patients waiting for liver transplantation were classified to hepatocellular carcinoma, indicating that some patients with long-lasting cirrhosis could have already gained hepatocellular carcinoma characteristics.
The signature can distinguish both hepatocellular carcinoma tissues and tumour-adjacent tissues from cirrhosis tissues of non-hepatocellular carcinoma patients even using inaccurately sampled biopsy specimens, which can aid early diagnosis of hepatocellular carcinoma.
目前，使用活检标本来确诊早期肝细胞癌的可疑病变并不完全可靠，因为采样量不足和采样位置不准确。因此，有必要开发一种生物标志物，以便即使采样位置不准确，也能辅助使用活检标本进行早期肝细胞癌诊断。
基于基因对的样本内相对表达顺序，我们确定了一种简单的定性标志物，用于区分肝细胞癌和癌旁组织与非肝细胞癌患者的肝硬化组织。
在训练数据集和 2 个大样本集（来自活检和手术切除标本）中验证了一个由 19 个基因对组成的标志物。对于活检标本，141 例肝细胞癌组织中有 95.7%和 108 例非肝细胞癌肝硬化组织中有 100%的组织被正确分类。特别是，60 例肝细胞癌旁正常组织和 80 例肝细胞癌旁肝硬化组织中的 100%和 77.5%被正确分类为肝细胞癌。对于手术切除标本，733 例肝细胞癌标本中有 99.7%被正确分类为肝细胞癌，而 254 例肝细胞癌旁肝硬化组织中有 96.1%和 538 例肝细胞癌旁正常组织中有 95.9%被正确分类为肝细胞癌。相比之下，47 例等待肝移植的非肝细胞癌患者的肝硬化中有 17.0%被误诊为肝细胞癌，表明一些长期肝硬化的患者可能已经获得了肝细胞癌的特征。
即使使用采样不准确的活检标本，该标志物也能区分非肝细胞癌患者的肝硬化组织与肝细胞癌组织和癌旁组织，有助于早期诊断肝细胞癌。
