无标签的nLC-MS/MS蛋白质组学分析显示结直肠癌组织与正常结肠粘膜之间的蛋白质组有显著差异。
Label-free nLC-MS/MS proteomic analysis reveals significant differences in the proteome between colorectal cancer tissues and normal colon mucosa.
发表日期:2023 Sep 14
作者:
Sezgin Zeren, Semih Seker, Gizem Akkaş Akgün, Emrah Okur, Azmi Yerlikaya
来源:
Epigenetics & Chromatin
摘要:
尽管已经发现了许多与癌症特征密切相关的驱动基因和乘客基因,但癌症治疗的进展并不令人满意。主要原因在于传统疗法既不具有选择性也不具有靶向性。另一个重要原因是由于突变和/或表观遗传变化的过度积累,癌细胞迅速产生对化疗药物的抗药性。鉴于此,我们认为发现新的靶点和关键基因/蛋白质可以改善治疗选择。在本研究中,首先通过右半结肠切除术或左半结肠切除术收集了结肠或直肠的组织样本(肿瘤和正常粘膜)。然后使用无标记的nLC-MS/MS方法进行蛋白质组学分析。我们确定了77个蛋白质在癌组织和正常粘膜之间的表达水平中存在统计学显著差异。虽然76个蛋白质的表达在癌组织中降低,但只有一个蛋白质(RNA结合基序蛋白_X染色体-RBMX)在结直肠癌组织中增加。我们使用生物信息学门户Metascape确定了涉及的生物过程。使用Clinical Proteomics Tumor Analysis Consortium(CPTAC)的数据,将77个在癌组织和正常组织之间表达有显著差异的蛋白质与UALCAN平台进行了比较。其中45个蛋白质的结果明显与CPTAC数据集匹配。Western blot研究证实,与正常粘膜相比,RBMX蛋白(在基因转录和各种预mRNA的替代剪接中起关键作用)的表达增加了2.04倍,而美蛋白质(一种具有抑制肿瘤功能的基质蛋白聚糖)明显减少了约6.04倍在肿瘤样本中。 ©2023年 Springer Science+Business Media, LLC, Springer Nature的独家授权。
Despite the discovery of numerous driving and passenger genes that play key roles in cancer characteristics, progress in cancer treatment has not been satisfactory. This is mainly because conventional therapies are neither selective nor targeted. Another important reason is that cancer cells rapidly develop resistance to chemotherapeutic agents due to excessive accumulation of mutations and/or epigenetic changes. In light of this, we believe that the discovery of new targets and key genes/proteins could improve treatment options. In this study, tissue samples (tumor and normal mucosa) were first collected from the colon or rectum by right or left hemicolectomy. Proteomic analysis was then performed using the label-free nLC-MS/MS method. We determined 77 proteins with statistically significant differences in expression levels between cancerous and normal mucosa. While the expression of 76 proteins was decreased in cancer tissues, only one protein (RNA-binding motif protein_X chromosome-RBMX) was increased in colorectal cancer tissues. The bioinformatics portal Metascape was used to determine the biological processes involved. 77 proteins with significantly different expression between cancerous and normal tissues were compared with the UALCAN platform using data from the Clinical Proteomics Tumor Analysis Consortium (CPTAC). The results for 45 of the 77 proteins clearly matched the CPTAC dataset. Western blot studies confirmed that RBMX protein (critical for gene transcription and alternative splicing of various pre-mRNAs) was increased 2.04-fold, while decorin protein (a matrix proteoglycan with tumor suppressor functions) was dramatically decreased by about 6.04-fold in tumor samples compared with normal mucosa.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.