血液基因标记早期肝癌检测

StephenW

J Clin Gastroenterol. 2015 Feb;49(2):150-7. doi: 10.1097/MCG.0000000000000112.
Blood gene signature for early hepatocellular carcinoma detection in patients with chronic hepatitis B.
Omar H1, Lim CR, Chao S, Lee MM, Bong CW, Ooi EJ, Yu CG, Tan SS, Abu Hassan MR, Menon J, Muthukaruppan R, Singh M, Nik Abdullah NA, Ooi BP, Ding RP, Low EJ, Tan F, Novak D, Harris DF, Yang H, Merican I, Liew CC.
Author information

    1*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.

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.

StephenW

Ĵ临床Gastroenterol。 2015年2月;49（2）：150-7。 DOI：10.1097/ MCG.0000000000000112。
治疗慢性乙型肝炎的血液基因标记早期肝癌检测
奥马尔H1，林CR，超S，李MM，奉CW，大井EJ，于CG，谭SS，阿布·哈桑·MR，农Ĵ，Muthukaruppan R，辛格男，聂阿卜杜拉NA，大井BP，丁RP，低EJ，谭楼诺瓦克D，哈里斯DF，杨H，美利肯我，刘氏CC。
作者信息

    1*士拉央医院，Lebuhraya士拉央，甲洞，黑风洞，雪兰莪之家分支伊赫桑†GeneNews（马来西亚）私人有限公司。转载必究，仪山癌症医院，丹绒武雅**岛医院，槟城§SultanahBahiyah医院，惹Langgar，亚罗士打，吉打∥Queen伊丽莎白医院，哥打京那巴鲁，沙巴¶Umum古晋砂拉越医院，惹敦·艾哈迈德·扎伊迪Adruce，古晋，沙捞越#Penang医院，惹Residensi††林华夷医院，槟城‡‡GeneNews诊断，办公室/实验室9，生物技术孵化中心，科技园马来西亚，吉隆坡，马来西亚‡GeneNews有限公司，列治文山，ON，加拿大§§Brigham妇科医院，哈佛大学医学院，波士顿，MA。

抽象
用途：

截至慢性乙型肝炎的25％（CHB）患者最终会发展肝细胞癌（HCC），疾病预后较差，除非及早发现。这项研究确定血液为基础的生物标志物RNA面板早期肝癌检测CHB。
材料和方法：

使用来自马来西亚的患者（HCC匹配，CHB，对照组）的血样中提取RNA进行全基因组RNA表达分析。基因的控制区分HCC被选定为使用实时定量聚合酶链反应进行进一步的测试。最后，一个6基因生物标志物被鉴定和表征使用训练集（队列I =126），并针对2测试集（队列II=222;队列III =174）进行测试。用于每个组的样本的总数是：肝癌+ CHB=143，CHB=211，对照=168。
结果：

我们的基因面板显示一致趋势，从我们的测试台控制区分HCC，根据0.9的世代III接收器操作特性曲线的区域。我们的独立的测试集（队列Ⅲ）表明，该基因的面板具有70％与92％的特异性，灵敏度。在小亚慢性乙型肝炎患者被检测一贯的HCC生物标记概况，从而有可能早期预测，癌症应该更深入的临床前筛选病例。
结论：

在本研究中鉴定的生物标记物可以被用作基于血液的测试的早期肝癌慢性乙型肝炎的检测的基础。