用于慢性乙型肝炎患者早期肝细胞癌检测的血液基因特征

Blood gene signature for early hepatocellular carcinoma detection in patients with chronic hepatitis B.

作者信息

Omar Haniza, Lim Chun Ren, Chao Samuel, Lee Michelle Mei Lin, Bong Chin Wei, Ooi Edie Jian Jiek, Yu Choon Geok, Tan Soek Siam, Abu Hassan Muhammad Radzi, Menon Jayaram, Muthukaruppan Raman, Singh Mandeep, Nik Abdullah Nik Azim, Ooi Boon Phoe, Ding Robert Phooi Huat, Low Eng Joo, Tan Francis, Novak David, Harris David F, Yang Hengxuan, Merican Ismail, Liew Choong-Chin

机构信息

*Selayang Hospital, Lebuhraya Selayang-Kepong, Batu Caves, Selangor Darul Ehsan †GeneNews (Malaysia) Sdn. Bhd., Mount Miriam Cancer Hospital, Tanjung Bungah **Island Hospital, Penang §Sultanah Bahiyah Hospital, Jalan Langgar, Alor Setar, Kedah ∥Queen Elizabeth Hospital, Kota Kinabalu, Sabah ¶Umum Kuching Sarawak Hospital, Jalan Tun Ahmad Zaidi Adruce, Kuching, Sarawak #Penang Hospital, Jalan Residensi ††Lam Wah Ee Hospital, Pulau Pinang ‡‡GeneNews Diagnostics, Office/Lab 9, Biotechnology Incubation Centre, Technology Park Malaysia, Kuala Lumpur, Malaysia ‡GeneNews Ltd., Richmond Hill, ON, Canada §§Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

出版信息

J Clin Gastroenterol. 2015 Feb;49(2):150-7. doi: 10.1097/MCG.0000000000000112.

DOI:10.1097/MCG.0000000000000112

PMID:25569223

Abstract

PURPOSE

Up to 25% of chronic hepatitis B (CHB) patients eventually develop hepatocellular carcinoma (HCC), a disease with poor prognosis unless detected early. This study identifies a blood-based RNA biomarker panel for early HCC detection in CHB.

MATERIALS AND METHODS

A genome-wide RNA expression study was performed using RNA extracted from blood samples from Malaysian patients (matched HCC, CHB, controls). Genes differentiating HCC from controls were selected for further testing using quantitative real-time polymerase chain reaction. Finally, a 6-gene biomarker panel was identified and characterized using a training set (cohort I = 126), and tested against 2 test sets (cohort II = 222; cohort III = 174). The total number of samples used for each group is: HCC + CHB = 143, CHB = 211, control = 168.

RESULTS

Our gene panel displays a consistent trend distinguishing HCC from controls in our test sets, with an area under receiver-operating characteristic curve of 0.9 in cohort III. Our independent test set (cohort III) showed that the gene panel had a sensitivity of 70% with a specificity of 92%. The biomarker profile for HCC was consistently detected in a small subgroup of CHB patients, thus potentially predicting early, preclinical cases of cancer that should be screened more intensively.

CONCLUSION

The biomarkers identified in this study can be used as the basis of a blood-based test for the detection of early HCC in CHB.

摘要

目的

高达25%的慢性乙型肝炎（CHB）患者最终会发展为肝细胞癌（HCC），除非早期发现，否则这种疾病的预后很差。本研究确定了一种基于血液的RNA生物标志物 panel，用于在CHB患者中早期检测HCC。

材料与方法

使用从马来西亚患者（匹配的HCC、CHB、对照）的血液样本中提取的RNA进行全基因组RNA表达研究。选择区分HCC与对照的基因，使用定量实时聚合酶链反应进行进一步测试。最后，使用训练集（队列I = 126）确定并表征了一个6基因生物标志物panel，并在2个测试集（队列II = 222；队列III = 174）上进行测试。每组使用的样本总数为：HCC + CHB = 143，CHB = 211，对照 = 168。

结果

我们的基因panel在测试集中显示出区分HCC与对照的一致趋势，队列III中受试者操作特征曲线下面积为0.9。我们的独立测试集（队列III）表明，该基因panel的敏感性为70%，特异性为92%。在一小部分CHB患者中始终检测到HCC的生物标志物特征性图谱，因此有可能预测早期临床前癌症病例，应对其进行更密集的筛查。