Conference Proceedings – 6th International Conference on Molecular Diagnostics and Biomarker Discovery (MDBD 2022): Building Resilience in Biomedical Research

Abstract

Background Tissue-based proteomics is an evolving tool used in cancer research to characterize the pathophysiology of disease. However, the proteome alterations involved in cervical carcinogenesis are not extensively studied. This study aims to elucidate the differentially expressed proteins and offer insights into the cellular processes and pathways involved in the development of cervical cancer. Methodology The pathological regions of interest in the cervical squamous epi-thelium were micro-dissected from formalin-fixed paraffin-embedded (FFPE) tissue sections of six normal cervix cases, five HPV-associated squamous intraepithelial lesion (SIL), and six squa-mous cell carcinomas (SCC). The samples were trypsin digestion and subjected to high throughput liquid chromatography-electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) and trapped ion mobility time-of-flight-mass spectrometry (tim-sTOF-MS), followed by quantification with MaxQuant and Perseus software. Bioinformatics analyses were carried out using DAVID, ConsensusPathDB, and STRING. Results and Discussion We identified a total of 3597 proteins with 589, 550, and 1570 proteins unique to the normal cervix, SIL, and SCC groups, respectively, while 332 proteins were similar across all three groups. The predominant protein found was histone. Interestingly, the quantification results showed an upward trend for the up-regulated proteins and a downward trend for the down-regulated proteins in the progression from normal to SIL and SCC. The main molecular function was the binding process, and the top biological processes were chromatin silencing for SIL compared to the normal cervix and nucleosome assembly for the SCC compared to SIL group. The key pathways involved were viral carcinogenesis and necroptosis, reflecting their role in cell proliferation, migration, and metastasis. Conclusion The identification of proteins and their associated pathways provides a deeper understanding of the underlying molecular mechanisms involved in HPV-associated cervical cancer.