Predictive model containing gene signature and shear wave elastography to predict patient outcomes after Kasai surgery in biliary atresia
Predictive model containing gene signature and shear wave elastography to predict patient outcomes after Kasai surgery in biliary atresia
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DOI：
10.1111/hepr.13948
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发表时间：
2023-08-08
影响因子：
4.2
通讯作者：
Zhou，Luyao
中科院分区：
文献类型：
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作者：
Wang，Guotao;Chen，Huadong;Zhou，Luyao
胆道闭锁（BA）的婴儿采用加塞门肠吻合术（KPE）治疗，但许多BA患者需要随后进行挽救性肝移植。本研究的目的是开发一个全面的基因临床模型的基础上二维剪切波弹性成像（2DSWE），肝脏基因表达，和其他临床参数，以预测响应KPE为BA patient.MethodsDifferentially BA（n= 102）和非BA对照（n= 14）的肝脏样本之间的差异表达基因模式进行了鉴定，使用RNA测序分析。然后将胆道闭锁患者随机分配到培训和验证队列。在训练队列中建立基于差异表达基因的基因分类器。进一步构建和验证了带和不带基因分类器的诺模图模型，用于预测BA患者的天然肝存活率。的实用性的列线图进行了比较，通过C-index.ResultsUsing最小绝对收缩和选择算子模型，我们生成了一个九基因预后分类。在训练队列中，与单独的基因分类器相比，基于九基因分类器、年龄、术前2DSWE和白蛋白的列线图具有更好的C指数（0.83 [0.76-0.90] vs. 0.69 [0.61-0.77]，p= 0.003）和验证队列（0.74 [0.67-0.82] vs. 0.62 [0.55-0.70]，p= 0.001）。使用从列线图中得出的风险评分，具有自体肝脏的BA患者的12个月生存率为35.7%（95%置信区间[CI]，22.7-56.3）和80.8%（95%CI，63.4-100.0）在低风险组的验证cohol.ConclusionsThe综合遗传临床诺模图的基础上术前2DSWE，肝脏基因表达和其他临床参数可以准确预测对KPE的反应。
AimsInfants with biliary atresia (BA) are treated with Kasai portoenterostomy (KPE) surgery, but many BA patients need subsequent salvage liver transplants. The aim of this study is to develop a comprehensive gene‐clinical model based on two‐dimensional shear wave elastography (2DSWE), liver gene expression, and other clinical parameters to predict response to KPE for BA patients.MethodsDifferentially expressed gene patterns between liver samples of BA (n= 102) and non‐BA control (n= 14) were identified using RNA sequencing analysis. Biliary atresia patients were then randomly assigned to training and validation cohorts. Gene classifier based on the differentially expressed genes was built in the training cohort. Nomogram models with and without gene classifier were further constructed and validated for predicting native liver survival of BA patients. The utility of the nomograms was compared by C‐index.ResultsUsing the least absolute shrinkage and selection operator model, we generated a nine‐gene prognostic classifier. The nomogram based on the nine‐gene classifier, age, preoperative 2DSWE, and albumin had the better C‐index compared to gene classifier alone in the training cohort (0.83 [0.76–0.90] vs. 0.69 [0.61–0.77],p= 0.003) and the validation cohort (0.74 [0.67–0.82] vs. 0.62 [0.55–0.70],p= 0.001). Using risk scores developed from the nomogram, the 12‐month survival rates of BA patients with native liver were 35.7% (95% confidence interval [CI], 22.7–56.3) in the high‐risk group and 80.8% (95% CI, 63.4–100.0) in the low‐risk group in the validation cohort.ConclusionsThe comprehensive genetic‐clinical nomogram based on preoperative 2DSWE, liver gene expression, and other clinical parameters can accurately predict response to KPE.