原发性肝癌立体定向体部放疗预后生物标志物的筛选
Screening of Prognostic Biomarkers for Stereotactic Body Radiation Therapy in Primary Liver Cancer.
作者信息
Liang Zhenzhen, Xue Chang, Chen Qing, Li Mengke, Li Guanghui, Feng Hao, Liu Yi, Liu Xiaodong, Ma Shumei
机构信息
School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China.
NHC Key Laboratory of Radiobiology (Jilin University), Changchun, Jilin, China.
出版信息
Dose Response. 2022 May 6;20(2):15593258221097589. doi: 10.1177/15593258221097589. eCollection 2022 Apr-Jun.
OBJECTIVE
So far there are still no effective immediate-early markers for assessing the efficacy of Stereotactic Body Radiation Therapy (SBRT). To find effective biomarkers for accurate assessment of the efficacy of SBRT in patients with primary liver cancer, we conducted this study including retrospective part and prospective part.
MATERIAL AND METHODS
589 patients with primary liver cancer were included at Ruikang Hospital affiliated to Guangxi Medical University from January 2012 to December 2018. Follow-up was conducted, clinical information and a total of 17 patients with 51 blood samples (before SBRT, before discharge and 2 months after SBRT) were collected. mRNAs profiles on 2 patients with 6 blood samples were detected by high-throughput sequencing, followed by qPCR verification on 15 patients with 45 blood samples.
RESULTS
The commonly used serum biomarkers such as AFP, CEA, and CA125 shown low prognostic value in distinguishing survival group and death group, indicated by low AUC (less than .7) and Youden indexes (less than .5). Based on high-throughput sequencing of test group and qPCR detection of another verification group, we found 16 up-regulated and 12 downregulated genes after SBRT. Among them, ADIPOR1 and EPB42 showed significantly different between effective and ineffective group after SBRT, ROC suggested that based on the optimal threshold of .5838, ADIPOR1 shown a sensitivity of 100% and a specificity of 83.33% to distinguish effective from ineffective group. And EPB42 had a sensitivity of 75% and a specificity of 100% at the optimal threshold of 1.3817. In addition, GSEA showed that high expression of ADIPOR1 was mainly related to Mismatch repair, Circadian rhythm, Protein processing in endoplasmic reticulum, DNA replication, and Fanconi anemia pathways.
CONCLUSION
ADIPOR1 in whole blood is a promising candidate to act as prognostic biomarker for predication of SBRT outcomes in primary liver cancer patients.
目的
目前仍没有有效的即时早期标志物用于评估立体定向体部放疗（SBRT）的疗效。为了找到有效的生物标志物以准确评估SBRT对原发性肝癌患者的疗效，我们开展了这项包括回顾性部分和前瞻性部分的研究。
材料与方法
纳入2012年1月至2018年12月在广西医科大学附属瑞康医院就诊的589例原发性肝癌患者。进行随访，收集临床信息，并采集了共17例患者的51份血样（SBRT前、出院前及SBRT后2个月）。通过高通量测序检测了2例患者6份血样的mRNA谱，随后对15例患者45份血样进行qPCR验证。
结果
常用的血清生物标志物如甲胎蛋白（AFP）、癌胚抗原（CEA）和糖类抗原125（CA125）在区分生存组和死亡组时预后价值较低，曲线下面积（AUC）低（小于0.7），约登指数（小于0.5）。基于测试组的高通量测序和另一验证组的qPCR检测，我们发现SBRT后有16个基因上调，12个基因下调。其中，脂肪组织特异性蛋白1（ADIPOR1）和红细胞膜收缩蛋白4.2（EPB42）在SBRT后的有效组和无效组之间存在显著差异，ROC曲线表明，基于最佳阈值0.5838，ADIPOR1区分有效组和无效组的灵敏度为100%，特异性为83.33%。而EPB42在最佳阈值1.3817时灵敏度为75%，特异性为100%。此外，基因集富集分析（GSEA）表明，ADIPOR1的高表达主要与错配修复、昼夜节律、内质网中的蛋白质加工、DNA复制和范可尼贫血途径有关。
结论
全血中的ADIPOR1有望作为预测原发性肝癌患者SBRT疗效的预后生物标志物。
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