School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China.
Center of Special Environmental Biomechanics & Biomedical Engineering, Northwestern Polytechnical University, Xi'an, Shaanxi, China.
Mol Genet Genomic Med. 2019 Jun;7(6):e693. doi: 10.1002/mgg3.693. Epub 2019 May 6.
Liver cancer is the fifth most common cancer, and hepatocellular carcinoma (HCC) is the major liver tumor type seen in adults. HCC is usually caused by chronic liver disease such as hepatitis B virus or hepatitis C virus infection. One of the promising treatments for HCC is liver transplantation, in which a diseased liver is replaced with a healthy liver from another person. However, recurrence of HCC after surgery is a significant problem. Therefore, it is important to discover reliable cellular biomarkers that can predict recurrence in HCC.
We analyzed previously published HCC RNA-Seq data that includes 21 paired tumor and normal samples, in which nine tumors were recurrent after orthotopic liver transplantation and 12 were nonrecurrent tumors with their paired normal samples. We used both the reference genome and de novo transcriptome assembly based analyses to identify differentially expressed genes (DEG) and used RandomForest to discover biomarkers.
We obtained 398 DEG using the Reference approach and 412 DEG using de novo assembly approach. Among these DEG, 258 genes were identified by both approaches. We further identified 30 biomarkers that could predict the recurrence. We used another independent HCC study that includes 50 patients normal and tumor samples. By using these 30 biomarkers, the prediction accuracy was 100% for normal condition and 98% for tumor condition. A group of Metallothionein was specifically discovered as biomarkers in both reference and de novo assembly approaches.
We identified a group of Metallothionein genes as biomarkers to predict recurrence. The metallothionein genes were all down-regulated in tumor samples, suggesting that low metallothionein expression may be a promoter of tumor growth. In addition, using de novo assembly identified some unique biomarkers, further confirmed the necessity of conducting a de novo assembly in human cancer study.
肝癌是第五大常见癌症，肝细胞癌（HCC）是成人中主要的肝脏肿瘤类型。HCC 通常由慢性肝病引起，如乙型肝炎病毒或丙型肝炎病毒感染。HCC 的一种有前途的治疗方法是肝移植，即将患病的肝脏替换为另一个人提供的健康肝脏。然而，手术后 HCC 的复发是一个重大问题。因此，发现可靠的细胞生物标志物来预测 HCC 的复发非常重要。
我们分析了之前发表的 HCC RNA-Seq 数据，其中包括 21 对肿瘤和正常样本，其中 9 个肿瘤在原位肝移植后复发，12 个肿瘤是无复发肿瘤，有其配对的正常样本。我们使用参考基因组和从头转录组组装分析来识别差异表达基因（DEG），并使用随机森林来发现生物标志物。
我们使用参考方法获得了 398 个 DEG，使用从头组装方法获得了 412 个 DEG。在这些 DEG 中，有 258 个基因是两种方法都鉴定出来的。我们进一步鉴定了 30 个可以预测复发的生物标志物。我们使用另一个包含 50 例正常和肿瘤样本的 HCC 独立研究。使用这 30 个生物标志物，正常情况下的预测准确率为 100%，肿瘤情况下的预测准确率为 98%。一组金属硫蛋白被特别发现为参考和从头组装方法中的生物标志物。
我们确定了一组金属硫蛋白基因作为预测复发的生物标志物。金属硫蛋白基因在肿瘤样本中均下调，表明低金属硫蛋白表达可能是肿瘤生长的促进因素。此外，使用从头组装方法鉴定了一些独特的生物标志物，进一步证实了在人类癌症研究中进行从头组装的必要性。
