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宫颈鳞状细胞癌无标记定量蛋白质组学分析鉴定潜在的蛋白质生物标志物。

Labeled-free quantitative proteomic analysis of cervical squamous cell carcinoma identifies potential protein biomarkers.

机构信息

Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei province, China.

出版信息

PeerJ. 2024 Jun 28;12:e17444. doi: 10.7717/peerj.17444. eCollection 2024.

Abstract

BACKGROUND

Cervical cancer remains a prevalent cancer among women, and reliance on surgical and radio-chemical therapies can irreversibly affect patients' life span and quality of life. Thus, early diagnosis and further exploration into the pathogenesis of cervical cancer are crucial. Mass spectrometry technology is widely applied in clinical practice and can be used to further investigate the protein alterations during the onset of cervical cancer.

METHODS

Employing labeled-free quantitative proteomics technology and bioinformatics tools, we analyzed and compared the differential protein expression profiles between normal cervical squamous cell tissues and cervical squamous cell cancer tissues. GEPIA is an online website for analyzing the RNA sequencing expression data of tumor and normal tissue data from the TCGA and the GTEx databases. This approach aided in identifying qualitative and quantitative changes in key proteins related to the progression of cervical cancer.

RESULTS

Compared to normal samples, a total of 562 differentially expressed proteins were identified in cervical cancer samples, including 340 up-regulated and 222 down-regulated proteins. Gene ontology functional annotation, and KEGG pathway, and enrichment analysis revealed that the differentially expressed proteins mainly participated in metabolic pathways, spliceosomes, regulation of the actin cytoskeleton, and focal adhesion signaling pathways. Specifically, desmoplakin (DSP), protein phosphatase 1, regulatory (inhibitor) subunit 13 like (PPP1R13L) and ANXA8 may be involved in cervical tumorigenesis by inhibiting apoptotic signal transmission. Moreover, we used GEPIA database to validate the expression of DSP, PPP1R13L and ANXA8 in human cancers and normal cervix.

CONCLUSION

In this study, we identified 562 differentially expressed proteins, and there were three proteins expressed higher in the cervical cancer tissues. The functions and signaling pathways of these differentially expressed proteins lay a theoretical foundation for elucidating the molecular mechanisms of cervical cancer.

摘要

背景

宫颈癌仍然是女性中常见的癌症,手术和放化疗的依赖会不可逆转地影响患者的寿命和生活质量。因此,早期诊断和进一步探讨宫颈癌的发病机制至关重要。质谱技术在临床实践中得到广泛应用,可以进一步研究宫颈癌发病过程中的蛋白质变化。

方法

采用无标记定量蛋白质组学技术和生物信息学工具,分析和比较正常宫颈鳞状细胞组织和宫颈鳞状细胞癌组织之间的差异蛋白表达谱。GEPIA 是一个在线网站,用于分析来自 TCGA 和 GTEx 数据库的肿瘤和正常组织数据的 RNA 测序表达数据。这种方法有助于确定与宫颈癌进展相关的关键蛋白质的定性和定量变化。

结果

与正常样本相比,在宫颈癌样本中总共鉴定出 562 个差异表达蛋白,其中 340 个上调,222 个下调。基因本体功能注释和 KEGG 通路富集分析表明,差异表达蛋白主要参与代谢途径、剪接体、肌动蛋白细胞骨架调节和焦点黏附信号通路。具体而言,桥粒斑蛋白(DSP)、蛋白磷酸酶 1、调节亚基 13 样(PPP1R13L)和膜联蛋白 A8(ANXA8)可能通过抑制凋亡信号转导参与宫颈癌的发生。此外,我们使用 GEPIA 数据库验证了 DSP、PPP1R13L 和 ANXA8 在人类癌症和正常宫颈中的表达。

结论

在这项研究中,我们鉴定出 562 个差异表达蛋白,其中 3 个蛋白在宫颈癌组织中表达较高。这些差异表达蛋白的功能和信号通路为阐明宫颈癌的分子机制奠定了理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6d8/11216203/289e88fc7fa8/peerj-12-17444-g001.jpg

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