Screening of Prognostic Biomarkers for Stereotactic Body Radiation Therapy in Primary Liver Cancer.
Screening of Prognostic Biomarkers for Stereotactic Body Radiation Therapy in Primary Liver Cancer.
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DOI：
10.1177/15593258221097589
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发表时间：
2022-04
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到目前为止，仍然没有有效的立即早期标记物来评估立体定向体部放射治疗（SBRT）的疗效。为了寻找有效的生物标志物来准确评估原发性肝癌患者SBRT的疗效，我们进行了这项研究，包括回顾性部分和前瞻性部分。纳入广西医科大学附属瑞康医院2012年1月至2018年12月的589例原发性肝癌患者。进行随访，收集17例患者的临床信息和51份血液样本（SBRT前、出院前和SBRT后2个月）。通过高通量测序检测2例患者6份血液样本的mRNA谱，然后对15例患者45份血液样本进行qPCR验证。常用的血清生物标志物如AFP、CEA和CA 125在区分存活组和死亡组中显示出低预后价值，表现为低AUC（小于0.7）和Youden指数（小于0.5）。通过对试验组的高通量测序和对另一验证组的qPCR检测，发现SBRT后有16个基因表达上调，12个基因表达下调。其中ADIPOR 1和EPB 42在SBRT后有效组和无效组间差异有统计学意义，ROC曲线提示，以0.5838为最佳阈值，ADIPOR 1区分有效组和无效组的敏感性为100%，特异性为83.33%。EPB 42在最佳阈值1.3817时的敏感性为75%，特异性为100%。GSEA结果显示ADIPOR 1的高表达主要与错配修复、昼夜节律、内质网蛋白质加工、DNA复制和Fanconi贫血通路有关。全血中的ADIPOR 1是一种有希望的候选者，可作为预测原发性肝癌患者SBRT结局的预后生物标志物。
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. 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. 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. ADIPOR1 in whole blood is a promising candidate to act as prognostic biomarker for predication of SBRT outcomes in primary liver cancer patients.