定量蛋白质组学分析宫颈癌组织鉴定与癌症进展相关的蛋白。
Quantitative Proteomic Analysis of Cervical Cancer Tissues Identifies Proteins Associated With Cancer Progression.
机构信息
Proteomics, Center for Genomic Sciences, The National Autonomous University of Mexico (UNAM), Cuernavaca, Mexico.
Division of Oncology, Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Lund, Sweden.
出版信息
Cancer Genomics Proteomics. 2022 Mar-Apr;19(2):241-258. doi: 10.21873/cgp.20317.
BACKGROUND/AIM: To date, several proteomics studies in cervical cancer (CC) have focused mainly on squamous cervical cancer (SCC). Our study aimed to discover and clarify differences in SCC and CAD that may provide valuable information for the identification of proteins involved in tumor progression, in CC as a whole, or specific for SCC or CAD.
MATERIALS AND METHODS
Total protein extracts from 15 individual samples corresponding to 5 different CC tissue types were compared with a non-cancerous control group using bidimensional liquid chromatography-mass spectrometry (2D LC-MS/MS), isobaric tags for relative and absolute quantitation (ITRAQ), principal component analysis (PCA) and gene set enrichment analysis (GSEA).
RESULTS
A total of 622 statistically significant different proteins were detected. Exocytosis-related proteins were the most over-represented, accounting for 25% of the identified and quantified proteins. Based on the experimental results, reticulocalbin 3 (RCN3) and Ras-related protein Rab-14 (RAB14) were chosen for further downstream in vitro and vivo analyses. RCN3 was overexpressed in all CC tissues compared to the control and RAB14 was overexpressed in squamous cervical cancer (SCC) compared to invasive cervical adenocarcinoma (CAD). In the tumor xenograft experiment, RAB14 protein expression was positively correlated with increased tumor size. In addition, RCN3-expressing HeLa cells induced a discrete size increment compared to control, at day 47 after inoculation.
CONCLUSION
RAB14 and RCN3 are suggested as potential biomarkers and therapeutic targets in the treatment of CC.
背景/目的：迄今为止，已有多项关于宫颈癌（CC）的蛋白质组学研究主要集中在鳞状宫颈癌（SCC）上。我们的研究旨在发现和阐明 SCC 和 CAD 之间的差异，这些差异可能为识别与肿瘤进展相关的蛋白质提供有价值的信息，这些蛋白质可能存在于整个 CC 中，也可能特异性存在于 SCC 或 CAD 中。
材料和方法
使用二维液相色谱-质谱联用（2D LC-MS/MS）、相对和绝对定量同位素标记（ITRAQ）、主成分分析（PCA）和基因集富集分析（GSEA）比较了 15 个对应于 5 种不同 CC 组织类型的个体样本的总蛋白提取物与非癌对照。
结果
共检测到 622 个具有统计学意义的差异蛋白。外排相关蛋白的表达最为显著，占鉴定和定量蛋白的 25%。根据实验结果，选择网钙蛋白 3（RCN3）和 Ras 相关蛋白 Rab-14（RAB14）进行进一步的体外和体内分析。与对照相比，所有 CC 组织中 RCN3 的表达均升高，与侵袭性宫颈腺癌（CAD）相比，SCC 中 RAB14 的表达升高。在肿瘤异种移植实验中，RAB14 蛋白表达与肿瘤体积增大呈正相关。此外，与对照相比，接种后第 47 天，表达 RCN3 的 HeLa 细胞诱导肿瘤大小略有增加。
结论
RAB14 和 RCN3 可作为 CC 治疗的潜在生物标志物和治疗靶点。
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