Cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC) are biliary tract cancers with poor five-year survival and high recurrence rates. Both CCA and GBC patients suffer from lack of circulating diagnostic biomarkers at the early stage. Extracellular vesicles, especially exosomes, have been emerged as promising diagnostic sources for cancers due to easy and quick accessibility. Hence, identification of exosomal biomarkers provides a novel strategy for CCA and GBC diagnosis. Here, five CCA patients and four GBC patients were enrolled for exosomal small RNA sequencing. Our data showed that exosomal piwi-interacting RNA (piRNA) populations were altered in the plasma of CCA and GBC patients. In comparison to healthy individuals, 694 and 323 piRNAs were upregulated in CCA and GBC, respectively, while 36 and 191 piRNAs were downregulated. Interestingly, sequencing results predicted that piR-2660989, piR-10506469, piR-20548188, piR-10822895, piR-hsa-23209, and piR-18044111 were upregulated in both CCA and GBC plasma. Importantly, we further included blood samples from 50 health individuals, 40 CCA patients, and 25 GBC patients and found that piR-10506469 were significantly increased in the exosomes of plasma from both CCA and GBC patients. Moreover, we analyzed the expression levels of differentially expressed exosomal piRNAs in the plasma of CCA and GBC patient before and after surgeries and found that piR-10506469 and piR-20548188 were significantly decreased in patients underwent surgeries. Taken together, our data revealed that exosomal piRNAs those are differentially expressed in CCA and GBC plasma may serve as potential biomarkers for the diagnosis of CCA and GBC.

中文翻译：

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外体piRNA分析显示胆管癌和胆囊癌独特的循环piRNA特征。

胆管癌（CCA）和胆囊癌（GBC）是五年生存期差且复发率高的胆道癌。CCA和GBC患者在早期都缺乏循环诊断生物标志物。细胞外囊泡，尤其是外来体，由于容易和快速的可及性而已成为有希望的癌症诊断来源。因此，外泌体生物标志物的鉴定为CCA和GBC诊断提供了一种新颖的策略。在此，招募了5位CCA患者和4位GBC患者进行外泌体小RNA测序。我们的数据显示，CCA和GBC患者血浆中的外泌体小卵磷脂相互作用RNA（piRNA）群体发生了改变。与健康个体相比，CCA和GBC中分别有694和323个piRNA上调，而36和191个piRNA被下调。有趣的是，测序结果预测piR-2660989，piR-10506469，piR-20548188，piR-10822895，piR-hsa-23209和piR-18044111在CCA和GBC血浆中均上调。重要的是，我们还包括了来自50名健康个体，40名CCA患者和25名GBC患者的血液样本，发现piR-10506469在CCA和GBC患者的血浆外泌体中均显着增加。此外，我们分析了手术前后CCA和GBC患者血浆中差异表达的外泌体piRNA的表达水平，发现进行手术的患者中piR-10506469和piR-20548188明显降低。综上所述，我们的数据表明，在CCA和GBC血浆中差异表达的外泌体piRNA可能作为诊断CCA和GBC的潜在生物标记。测序结果预测，在CCA和GBC血浆中，piR-2660989，piR-10506469，piR-20548188，piR-10822895，piR-hsa-23209和piR-18044111均被上调。重要的是，我们还包括了来自50名健康个体，40名CCA患者和25名GBC患者的血液样本，发现piR-10506469在CCA和GBC患者的血浆外泌体中均显着增加。此外，我们分析了手术前后CCA和GBC患者血浆中差异表达的外泌体piRNA的表达水平，发现进行手术的患者中piR-10506469和piR-20548188明显降低。综上所述，我们的数据表明，在CCA和GBC血浆中差异表达的外泌体piRNA可能作为诊断CCA和GBC的潜在生物标记。测序结果预测，在CCA和GBC血浆中，piR-2660989，piR-10506469，piR-20548188，piR-10822895，piR-hsa-23209和piR-18044111均被上调。重要的是，我们还包括了来自50名健康个体，40名CCA患者和25名GBC患者的血液样本，发现piR-10506469在CCA和GBC患者的血浆外泌体中均显着增加。此外，我们分析了手术前后CCA和GBC患者血浆中差异表达的外泌体piRNA的表达水平，发现进行手术的患者中piR-10506469和piR-20548188明显降低。综上所述，我们的数据表明，在CCA和GBC血浆中差异表达的外泌体piRNA可能作为诊断CCA和GBC的潜在生物标记。