STAT1 expression and HPV16 viral load predict cervical lesion progression

Abstract

Cervical cancer is the fourth leading cause of cancer-associated mortality worldwide. However, its underlying molecular mechanisms are unclear. It is important to explore these mechanisms in order to identify novel diagnostic and prognostic biomarkers. The present study determined the association between STAT1 and human papillomavirus (HPV)16 in cervical lesions. STAT1 expression was detected by immunohistochemistry. Quantitative PCR was used to detect HPV16 viral load and STAT1 expression in cervical lesions. The potential associations among STAT1 expression, HPV16 viral load and the severity of cervical lesions in patients were analyzed using receiver operating characteristic (ROC) curves. The Cancer Genome Atlas database was used to analyze STAT1 expression and survival. High STAT1 expression was observed in 10.71 (3/28), 41.18 (14/34), 53.06 (26/49) and 90.00% (27/30) of normal tissue, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and cervical squamous cell carcinoma samples, respectively. The HPV16 copy number gradually increased with the progression of cervical lesions, with the highest copy number observed in cervical cancer samples. In addition, STAT1 expression was positively correlated with HPV16 viral load. Furthermore, ROC curve analysis demonstrated that the combination of STAT1 expression and HPV16 viral load was able to differentiate between LSIL/HSIL and cervical cancer samples. Bioinformatics analysis revealed that STAT1 expression was associated with improved survival in cervical cancer. Additionally, STAT1 expression was positively associated with the progression of cervical lesions, and HPV16 viral load may affect STAT1 expression. Overall, these findings indicate that STAT1 may be an indicator of the status of cervical lesions.

Nuclear factor IB is downregulated in vulvar squamous cell carcinoma (VSCC): Unravelling differentially expressed genes in VSCC through gene expression dataset analysis

“…Our results regarding IHC-expression of STAT1 were in contrast to those of a recent study, which reported a higher STAT1-expression in cervical intraepithelial neoplasia (CIN) than in normal cervical epithelium, and deduced an association of increased STAT1-expression with malignant progression of CIN ( 26 ). Since STAT-1 expression is regulated by a complex network of interferons, we speculate that the difference in expression between vulvar and cervical tissue could be ascribed to the dissimilar microenvironments of these anatomical sites.…”

“…For all tissue types, diffuse, cytoplasmic STAT1-expression of moderate-to-strong intensity was noted across full epithelial thickness. STAT1 is a component of the Janus kinase (JAK)-STAT signaling pathway, and can act as an antimicrobial mediator, a tumor suppressor, or a promotor of tumor progression ( 26 ). Aberrant expression of STAT1 in HPV-related lesions is considered to reflect activation of the JAK-STAT pathway as a consequence of the inflammatory response induced by HPV ( 26 ).…”

Molecular Differences Between Squamous Cell Carcinoma and Adenocarcinoma Cervical Cancer Subtypes: Potential Prognostic Biomarkers

“…Given that ADC and SCC have frequently HPV 18 and 16, respectively, it is expected that this pathway is altered in both subtypes, nonetheless we were able to distinguish that it is enriched in the SCC subtype, which is an interesting fact that has yet to be validated. However, Wu S. and collaborators, reported that STAT1 expression, a member of this pathway, was positively correlated with HPV 16 viral load [33]. Therefore, if the SCC subtype has a higher HPV16 load, an increase activation of this pathway is expected.…”

Bovine Delta Papillomavirus E5 Oncoprotein Interacts With TRIM25 and Hampers Antiviral Innate Immune Response Mediated by RIG-I-Like Receptors

“…It is well known that physical status of the virus (episomal or integrated forms) may generate variability in the host innate antiviral response ( 15 ). Therefore, a protein can be both downregulated by episomal papillomavirus and upregulated by integrated papillomavirus in infected cells being its expression positively associated with the progression of lesions ( 37 , 38 ). The lack of correlation between viral load and the expression of the studied antiviral immune response factors suggests that viral replication is not determinant in the E5-mediated downregulation of host immune responses.…”