Plasma exosome miR-196a and miR-1246 are potential indicators of localized pancreatic cancer.

Plasma exosome miR-196a and miR-1246 are potential indicators of localized pancreatic cancer.
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DOI:
10.18632/oncotarget.20332
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发表时间:
2017-09-29
期刊:
影响因子:
--
通讯作者:
Ding WQ
Ding WQ
中科院分区:
其他
文献类型:
--
作者:
Xu YF;Hannafon BN;Zhao YD;Postier RG;Ding WQ

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局限性胰腺癌(I期和IIA期)患者的生存率比晚期患者高得多,但早期发现仍然是这种恶性肿瘤的挑战。本研究的目的是评估外泌体miRNA特征是否指示局部胰腺癌。从胰腺癌细胞系的条件培养基和局部胰腺癌患者(I-IIA期,n=15)和健康受试者(n=15)的血浆样品中收集外泌体。通过下一代小RNA测序分析来自胰腺癌细胞系的细胞和外泌体miRNA。通过qRT-PCR分析血浆外泌体miRNA表达。我们发现某些miRNA,如miR-196 a和miR-1246,在胰腺癌外泌体中高度富集。一致地,与健康受试者相比,胰腺癌患者的血浆外泌体miR-196 a和miR-1246水平显著升高。对癌症亚型的分析表明,血浆外泌体miR-196 a是胰腺导管腺癌(PDAC)的更好指标,而血浆外泌体miR-1246在导管内乳头状粘液性肿瘤(IPMN)患者中显著升高。相比之下,胰腺神经内分泌肿瘤(NET)患者和健康受试者之间的血浆外泌体miR-196 a和miR-1246水平没有差异。总之,我们证明某些miRNA种类,例如miR-196 a和miR-1246,在胰腺癌外泌体中高度富集,并且在局部胰腺癌患者的血浆外泌体中含量升高。
Patients with localized pancreatic cancer (stage I and stage IIA) have a much higher survival rate than those presenting at later stages, yet early detection remains a challenge to this malignancy. The aim of this study was to evaluate whether exosome miRNA signatures are indicative of localized pancreatic cancer. Exosomes were collected from the conditioned media of pancreatic cancer cell lines and plasma samples of localized pancreatic cancer patients (Stage I-IIA, n=15), and healthy subjects (n=15). Cellular and exosome miRNAs from pancreatic cancer cell lines were profiled by next-generation small RNA sequencing. Plasma exosome miRNA expression was analyzed by qRT-PCR. We found that certain miRNAs, such as miR-196a and miR-1246, are highly enriched in pancreatic cancer exosomes. Consistently, plasma exosome miR-196a and miR-1246 levels were significantly elevated in pancreatic cancer patients as compared to healthy subjects. An analysis of the cancer subtypes indicated that plasma exosome miR-196a is a better indicator of pancreatic ductal adenocarcinoma (PDAC), whereas plasma exosome miR-1246 is significantly elevated in patients with intraductal papillary mucinous neoplasms (IPMN). In contrast, there were no differences in the plasma exosome miR-196a and miR-1246 levels between patients with pancreatic neuroendocrine tumors (NET) and healthy subjects. In conclusion, we demonstrate that certain miRNA species, such as miR-196a and miR-1246, are highly enriched in pancreatic cancer exosomes and elevated in plasma exosomes of patients with localized pancreatic cancer.
MicroRNA-1246与CCNG2介导的化学耐药性和胰腺癌的干性相关的表达。
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