Chua-On Daraporn, Proungvitaya Tanakorn, Techasen Anchalee, Limpaiboon Temduang, Roytrakul Sittiruk, Wongkham Sopit, Wongkham Chaisiri, Somintara Ongart, Sungkhamanon Sakkarn, Proungvitaya Siriporn
Centre of Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.
Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
Tumour Biol. 2016 Oct;37(10):13659-13667. doi: 10.1007/s13277-016-5204-x. Epub 2016 Jul 29.
Prognosis of cholangiocarcinoma (CCA) patients is absolutely poor in spite of extensive efforts for the development of chemotherapy. Mitochondrial proteins play key roles in carcinogenesis of various cancers. Therefore, mitochondria are considered as the target organelles for chemotherapy of several cancers including CCA. The purpose of this study is to identify potential candidate proteins for chemotherapy using mitochondrial proteome analysis for CCA tissues. A shotgun proteomic approach using SDS-PAGE coupled with LC-MS/MS was applied to compare the expression of mitochondrial proteins in CCA and the adjacent non-cancerous tissues. Using the proteomic analysis for the pooled mitochondrial proteins purified from three each of papillary and non-papillary types of CCA and their adjacent tissues, 281 proteins were identified as mitochondrial proteins, and 105 of them have significantly different expression levels compared with the corresponding counterparts. Among the 105 proteins, apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) was a unique protein commonly over-expressed in both papillary and non-papillary types of CCA tissues but not in the adjacent non-cancerous tissues. In conclusion, AIFM3 was aberrantly expressed only in the mitochondria of CCA tissues. This finding suggests that AIFM3 could be a potential target molecule for CCA chemotherapy.
尽管在开发化疗方法方面付出了巨大努力，但胆管癌（CCA）患者的预后仍然极差。线粒体蛋白在各种癌症的发生过程中起着关键作用。因此，线粒体被认为是包括CCA在内的几种癌症化疗的靶细胞器。本研究的目的是通过对CCA组织进行线粒体蛋白质组分析，确定潜在的化疗候选蛋白。采用SDS-PAGE结合LC-MS/MS的鸟枪法蛋白质组学方法，比较CCA组织和相邻非癌组织中线粒体蛋白的表达。通过对从乳头状和非乳头状CCA及其相邻组织各三个样本中纯化的线粒体蛋白进行蛋白质组分析，共鉴定出281种线粒体蛋白，其中105种与相应对照相比表达水平有显著差异。在这105种蛋白质中，线粒体相关凋亡诱导因子3（AIFM3）是一种独特的蛋白质，在乳头状和非乳头状CCA组织中均普遍过表达，但在相邻非癌组织中未过表达。总之，AIFM3仅在CCA组织的线粒体中异常表达。这一发现表明，AIFM3可能是CCA化疗的潜在靶分子。
