Tandem mass tag-based quantitative proteomic analysis of cervical cancer.

BACKGROUND: Cervical cancer is a common cancer in women caused by high-risk human papillomavirus (Hr-HPV). Many potential biomarkers have been proposed for precancerous lesions and cancer diagnosis and some of these markers studied for prognosis. This study determined potential biomarkers for cervical cancer diagnosis in regard to HPV genotype by using isobaric labeling quantitative proteomics. METHODS: in the current study, there were 75 formalin fixed paraffin embedded (FFPE) uterine cervical samples that used to determine the 14 HPV genotypes and the viral load of each genotype was determined. The tandem mass tag (TMT) proteomic work was performed on four FFPE samples of cervical cancer and four FFPE of control samples. The validation of biomarkers from cervical proteome were evaluated using Immunohistochemistry (IHC) testing. RESULTS: The most frequent HPV genotype among all other genotypes was HPV 16. There were 2753 proteins quantified by TMT and 336 of these proteins had significant differential abundances. KPNA2, MCM2, COL1A1, and DCN were selected based on functional enrichment analysis and validated by Immunohistochemistry (IHC) testing. The staining of IHC confirmed the upregulation of KPNA2 and MCM2 expression in cervical neoplasia and the downregulation of DCN and COL1A1 in some cervical cancer group subjects. CONCLUSION: The KPNA2 marker was compared to other previously reported biomarkers and is a putative biomarker to be validated in further studies, specifically the relationship with HPV load.