Plasma-Derived Exosomal ALIX as a Novel Biomarker for Diagnosis and Classification of Pancreatic Cancer.
Plasma-Derived Exosomal ALIX as a Novel Biomarker for Diagnosis and Classification of Pancreatic Cancer.
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血浆来源的外泌体 ALIX 作为胰腺癌诊断和分类的新型生物标志物
DOI：
10.3389/fonc.2021.628346
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Yang J;Zhang Y;Gao X;Yuan Y;Zhao J;Zhou S;Wang H;Wang L;Xu G;Li X;Wang P;Zou X;Zhu D;Lv Y;Zhang S
背景胰腺癌（Pancreatic cancer，PC）早期症状隐匿，早期发现率低，预后差。外泌体可以由各种细胞类型释放，并且倾向于成为用于PC检测的潜在的新型生物标志物。在这项研究中，我们探讨了血浆外泌体的蛋白质组学谱收集PC患者在不同阶段和其他胰腺疾病。方法收集6组患者的血浆标本，包括I/II期胰腺癌、III/IV期胰腺癌、高分化胰腺神经内分泌肿瘤（P-NET）、胰腺囊性病变（PCLs）、慢性胰腺炎（CP）和健康对照（HC）。通过超离心分离血浆来源的外泌体并常规鉴定。进行基于相对和绝对定量的同位素标记（iTRAQ）的蛋白质组学分析沿着生物信息学分析以阐明蛋白质的生物学功能。通过酶联免疫吸附试验在更大的患者队列中进一步证实了外泌体阿利克斯的表达。此外，受试者工作特征曲线分析应用于评估阿利克斯作为新的诊断生物标志物的潜力。结果蛋白质组学分析显示，6组胰腺组织中共有623个蛋白质表达，其中16个蛋白质在PC与其他胰腺疾病（包括P-NET、PCLs和CP）中的丰度存在差异。基于蛋白质组学和生物信息学分析的结果，随后选择外泌体阿利克斯作为用于PC检测的新型生物标志物，并在另一个临床队列中进行验证。我们发现阿利克斯在PC患者中的表达高于其他胰腺疾病或HC患者，并且与TNM分期和远处转移密切相关。有趣的是，外泌体阿利克斯和血清CA 199的组合在区分早期与晚期PC（AUC值0.872）和PC与其他胰腺疾病（AUC值0.910）方面比单独的阿利克斯或CA 199具有更大的值。结论基于蛋白质组学分析，血浆来源exosomes蛋白可作为PC临床诊断的理想非侵入性生物标志物。重要的是，外泌体阿利克斯与CA 199的组合在PC的检测中具有很大的潜力，特别是在区分早期和晚期PC患者方面。
Background Pancreatic cancer (PC) has a dismal prognosis due to its insidious early symptoms and poor early detection rate. Exosomes can be released by various cell types and tend to be a potential novel biomarker for PC detection. In this study, we explored the proteomic profiles of plasma exosomes collected from patients with PC at different stages and other pancreatic diseases. Methods Plasma samples were collected from six groups of patients, including PC at stage I/II, PC at stage III/IV, well-differentiated pancreatic neuroendocrine tumor (P-NET), pancreatic cystic lesions (PCLs), chronic pancreatitis (CP), and healthy controls (HCs). Plasma-derived exosomes were isolated by ultracentrifugation and identified routinely. Isobaric tags for relative and absolute quantification (iTRAQ) based proteomic analysis along with bioinformatic analysis were performed to elucidate the biological functions of proteins. The expression of exosomal ALIX was further confirmed by enzyme-linked immunosorbent assay in a larger cohort of patients. Furthermore, receiver operating characteristic curve analysis was applied to evaluate the potential of ALIX as a novel diagnostic biomarker. Results The proteomic profile revealed a total of 623 proteins expressed among the six groups, and 16 proteins with differential degrees of abundance were found in PC vs. other pancreatic diseases (including P-NET, PCLs, and CP). Based on the results of proteomic and bioinformatic analyses, exosomal ALIX was subsequently selected as a novel biomarker for PC detection and validated in another clinical cohort. We noticed that ALIX expression was elevated in PC patients compared with patients with other pancreatic diseases or HC, and it was also closely associated with TNM stage and distant metastasis. Interestingly, the combination of exosomal ALIX and serum CA199 has greater values in differentiating both early vs. late PC (AUC value 0.872) and PC vs. other pancreatic diseases (AUC value 0.910) than either ALIX or CA199 alone. Conclusion In summary, our study demonstrated that based on proteomic profiling, proteins isolated from the plasma-derived exosomes may function as ideal non-invasive biomarkers for the clinical diagnosis of PC. Importantly, exosomal ALIX combined with CA199 has great potentials in detection of PC, especially in distinguishing PC patients at early stages from advanced stages.
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影响因子：
16
作者：
Lötvall J;Hill AF;Hochberg F;Buzás EI;Di Vizio D;Gardiner C;Gho YS;Kurochkin IV;Mathivanan S;Quesenberry P;Sahoo S;Tahara H;Wauben MH;Witwer KW;Théry C
通讯作者：
Théry C
影响因子：
9.7
作者：
Lai X;Wang M;McElyea SD;Sherman S;House M;Korc M
通讯作者：
Korc M
影响因子：
--
作者：
Frampton AE;Prado MM;López-Jiménez E;Fajardo-Puerta AB;Jawad ZAR;Lawton P;Giovannetti E;Habib NA;Castellano L;Stebbing J;Krell J;Jiao LR
通讯作者：
Jiao LR
影响因子：
5.7
作者：
Jin H;Liu P;Wu Y;Meng X;Wu M;Han J;Tan X
通讯作者：
Tan X
影响因子：
8.8
作者：
Liu X;Zheng W;Wang W;Shen H;Liu L;Lou W;Wang X;Yang P
通讯作者：
Yang P