Label-based comparative proteomics of oral mucosal tissue to understand progression of precancerous lesions to oral squamous cell carcinoma

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemistry and Biophysics Reports Pub Date : 2024-10-13 DOI:10.1016/j.bbrep.2024.101842
Vipra Sharma , Sundararajan Baskar Singh , Sabyasachi Bandyopadhyay , Kapil Sikka , Aanchal Kakkar , Gururao Hariprasad
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引用次数: 0

Abstract

Introduction

Oral squamous cell carcinomas typically arise from precancerous lesions such as leukoplakia and erythroplakia. These lesions exhibit a range of histological changes from hyperplasia to dysplasia and carcinoma in situ, during their transformation to malignancy. The molecular mechanisms driving this multistage transition remain incompletely understood. To bridge this knowledge gap, our current study utilizes label based comparative proteomics to compare protein expression profiles across different histopathological grades of leukoplakia, erythroplakia, and oral squamous cell carcinoma samples, aiming to elucidate the molecular changes underlying lesion evolution.

Methodology

An 8-plex iTRAQ proteomics of 4 biological replicates from 8 clinical phenotypes of leukoplakia and erythroplakia, with hyperplasia, mild dysplasia, moderate dysplasia; along with phenotypes of well differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinoma was carried out using the Orbitrap Fusion Lumos mass spectrometer. Raw files were processed with Maxquant, and statistical analysis across groups was conducted using MetaboAnalyst. Statistical tools such as ANOVA, PLS-DA VIP scoring, and correlation analysis were employed to identify differentially expressed proteins that had a linear expression variation across phenotypes of hyperplasia to cancer. Validation was done using Bioinformatic tools such as ClueGO + Cluepedia plugin in Cytoscape to extract functional annotations from gene ontology and pathway databases.

Results and discussion

A total of 2685 protein groups and 12,397 unique peptides were identified, and 61 proteins consistently exhibited valid reporter ion corrected intensities across all samples. Of these, 6 proteins showed linear varying expression across the analysed sample phenotypes. Collagen type VI alpha 2 chain (COL6A2), Fibrinogen β chain (FGB), and Vimentin (VIM) were found to have increased linear expression across pre-cancer phenotypes of leukoplakia to cancer, while Annexin A7 (ANXA7) was seen to be having a linear decreasing expression. Collagen type VI alpha 2 chain (COL6A2) and Annexin A2 (ANXA2) had increased linear expression across precancer phenotypes of erythroplakia to cancer. The mass spectrometry proteomics data have been deposited to the ProteomeXchanger Consortium via the PRIDE partner repository with the data set identifier PXD054190. These differentially expressed proteins mediate cancer progression mainly through extracellular exosome; collagen-containing extracellular matrix, hemostasis, platelet aggregation, and cell adhesion molecule binding.

Conclusion

Label-based proteomics is an ideal platform to study oral cancer progression. The differentially expressed proteins provide insights into the molecular mechanisms underlying the progression of oral premalignant lesions to malignant phenotypes. The study has translational value for early detection, risk stratification, and potential therapeutic targeting of oral premalignant lesions and in its prevention to malignant forms.
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基于标签的口腔黏膜组织比较蛋白质组学,了解癌前病变到口腔鳞状细胞癌的发展过程
导言:口腔鳞状细胞癌通常源于癌前病变,如白斑病和红斑病。这些病变在向恶性肿瘤转化的过程中会出现一系列组织学变化,从增生到发育不良和原位癌。驱动这种多阶段转变的分子机制仍不完全清楚。为了弥补这一知识空白,我们目前的研究利用基于标记的比较蛋白质组学比较了不同组织病理学等级的白斑病、红斑病和口腔鳞状细胞癌样本的蛋白质表达谱,旨在阐明病变演变的分子变化。方法 使用 Orbitrap Fusion Lumos 质谱仪对白斑病和红斑病的 8 种临床表型(增生、轻度发育不良、中度发育不良)以及分化良好的鳞状细胞癌和中度分化的鳞状细胞癌表型的 4 个生物重复样本进行了 8 重 iTRAQ 蛋白组学分析。使用 Maxquant 处理原始文件,并使用 MetaboAnalyst 进行跨组统计分析。采用方差分析、PLS-DA VIP 评分和相关性分析等统计工具来识别从增生到癌症的不同表型中具有线性表达变化的差异表达蛋白。利用Cytoscape中的ClueGO + Cluepedia插件等生物信息学工具从基因本体论和通路数据库中提取功能注释进行验证。其中,6 种蛋白质在分析样本表型中的表达呈线性变化。在从白斑病到癌症的癌前表型中,六型胶原蛋白α2链(COL6A2)、纤维蛋白原β链(FGB)和波形蛋白(VIM)的线性表达量增加,而Annexin A7(ANXA7)的线性表达量下降。六型胶原α2链(COL6A2)和Annexin A2(ANXA2)在红斑狼疮到癌症的癌前表型中的线性表达增加。质谱蛋白质组学数据已通过 PRIDE 合作伙伴存储库存入 ProteomeXchanger Consortium,数据集标识符为 PXD054190。这些差异表达的蛋白质主要通过细胞外基质、含胶原的细胞外基质、止血、血小板聚集和细胞粘附分子结合介导癌症进展。差异表达的蛋白质有助于深入了解口腔癌前病变向恶性表型发展的分子机制。这项研究对于口腔癌前病变的早期检测、风险分层、潜在治疗目标以及预防恶性病变具有转化价值。
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来源期刊
Biochemistry and Biophysics Reports
Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
4.60
自引率
0.00%
发文量
191
审稿时长
59 days
期刊介绍: Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.
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