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感染及相关胆管癌的新型潜在生物标志物

Novel Potential Biomarkers for Infection and Associated Cholangiocarcinoma.

作者信息

Aksorn Nithikoon, Roytrakul Sittiruk, Kittisenachai Suthathip, Leelawat Kawin, Chanvorachote Pithi, Topanurak Supachai, Hamano Shinjiro, Lek-Uthai Usa

机构信息

Doctor of Public Health Programme (Parasitology), Faculty of Graduate Studies, Mahidol University, Bangkok, Thailand.

Department of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok, Thailand.

出版信息

In Vivo. 2018 Jul-Aug;32(4):871-878. doi: 10.21873/invivo.11321.

Abstract

BACKGROUND/AIM: Early detection of disease is a pivotal factor for determining prognosis and clinical outcome of patients with cancer. As cholangiocarcinoma (CCA) is currently difficult to detect and most cases of such cancer present with late-stage disease at the time of initial diagnosis, we employed proteomic analysis of the bile to identify potential candidate biomarkers for Opisthorchis viverrini (OV)-associated CCA.

MATERIALS AND METHODS

Proteins in pooled bile samples from patients with CCA and OV infection, with CCA without OV infection, with OV infection but no CCA, and with neither OV infection nor CCA were separated by 15% sodium dodecyl sulfate-polyacrylamide gel electrophoresis, in-gel trypsin digestion and analyzed by liquid chromatography-tandem mass spectrometry.

RESULTS

According to our analysis, three proteins, namely aristaless-like homeobox1 isoform X1 (ALX1), major histocompatibility complex polypeptide-related sequence A (MICA), and uncharacterized protein C14orf105 isoform X12 were found to be potential markers for OV infection, as they were predominantly found in all OV-infected groups. Although these proteins were detected in both OV-infected patients with and without CCA, their abundance was 2.90-, 7.06-and 3.65-fold higher, respectively, in those with CCA. In patients with CCA, potential novel biomarkers wre immunoglobulin heavy chain, translocated in liposarcoma (TLS), visual system homeobox 2 (VSX2) and an unnamed protein product.

CONCLUSION

We provided novel information regarding potential biomarkers for OV infection and CCA. These two protein profiles could benefit diagnosis as well as monitoring of CCA.

摘要

背景/目的:疾病的早期检测是决定癌症患者预后和临床结局的关键因素。由于胆管癌(CCA)目前难以检测,且大多数此类癌症病例在初诊时已处于晚期,我们对胆汁进行了蛋白质组分析,以确定与华支睾吸虫(OV)相关的CCA的潜在候选生物标志物。

材料与方法

通过15%十二烷基硫酸钠-聚丙烯酰胺凝胶电泳、胶内胰蛋白酶消化,对来自患有CCA和OV感染、患有CCA但无OV感染、患有OV感染但无CCA以及既无OV感染也无CCA的患者的混合胆汁样本中的蛋白质进行分离,并通过液相色谱-串联质谱分析。

结果

根据我们的分析,发现无翅型同源盒蛋白1亚型X1(ALX1)、主要组织相容性复合体多肽相关序列A(MICA)和未表征蛋白C14orf105亚型X12这三种蛋白质是OV感染的潜在标志物,因为它们主要在所有OV感染组中被发现。尽管在患有和未患有CCA的OV感染患者中均检测到了这些蛋白质,但在患有CCA的患者中,它们的丰度分别高出2.90倍、7.06倍和3.65倍。在患有CCA的患者中,潜在的新型生物标志物有免疫球蛋白重链、脂肪肉瘤转移蛋白(TLS)、视觉系统同源盒2(VSX2)和一种未命名的蛋白质产物。

结论

我们提供了有关OV感染和CCA潜在生物标志物的新信息。这两种蛋白质谱可能有助于CCA的诊断和监测。

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