Aljawad Mohammed F, Faisal Abdul Hussein M Al, Alqanbar Mohammed F, Wilmarth Phillip A, Hassan Basima Q
Genetic Engineering and Biotechnology Institute, University of Baghdad, Baghdad, Iraq.
Department of Pathology, College of Medicine, University of Kerbala, Baghdad, Iraq.
Proteomics Clin Appl. 2023 Jan;17(1):e2100105. doi: 10.1002/prca.202100105. Epub 2022 Sep 6.
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.
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.
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.
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.
宫颈癌是由高危型人乳头瘤病毒（Hr-HPV）引起的常见女性癌症。已提出许多潜在生物标志物用于癌前病变和癌症诊断，其中一些标志物也用于预后研究。本研究采用等压标记定量蛋白质组学方法确定与HPV基因型相关的宫颈癌诊断潜在生物标志物。
在本研究中，共75例福尔马林固定石蜡包埋（FFPE）子宫颈样本用于确定14种HPV基因型，并测定每种基因型的病毒载量。对4例宫颈癌FFPE样本和4例对照FFPE样本进行串联质谱标签（TMT）蛋白质组学研究。采用免疫组织化学（IHC）检测对来自宫颈蛋白质组的生物标志物进行验证。
在所有其他基因型中，最常见的HPV基因型是HPV 16。通过TMT定量了2753种蛋白质，其中336种蛋白质具有显著的丰度差异。基于功能富集分析选择了核转运蛋白α2（KPNA2）、微小染色体维持蛋白2（MCM2）、I型胶原蛋白α1链（COL1A1）和核心蛋白聚糖（DCN），并通过免疫组织化学（IHC）检测进行验证。IHC染色证实了KPNA2和MCM2在宫颈肿瘤中的表达上调，以及DCN和COL1A1在一些宫颈癌组受试者中的表达下调。
将KPNA2标志物与其他先前报道的生物标志物进行了比较，它是一种有待在进一步研究中验证的推定生物标志物，特别是其与HPV载量的关系。
