Identification of differentially expressed genes and pathways for risk stratification in HPV-associated cancers governing different anatomical sites

Abstract

Background: Human papillomavirus (HPV) is the major cause of cervical cancer (CC) etiology; its contribution to head and neck cancer (HNC) incidence is steadily increasing. As individual patients' response to the treatment of HPV-associated cancer is variable, there is a pressing need for the identification of biomarkers for risk stratification that can help determine the intensity of treatment. Methods:We have previously reported a novel prognostic and predictive indicator (HPPI) scoring system in HPV-associated cancers regardless of anatomical location by analyzing The Cancer Genome Atlas and Gene Expression Omnibus databases. In the present study, we comprehensively investigated the association of group-specific expression patterns of common differentially expressed genes (DEGs) between high-and low-risk groups in HPV-associated CC and HNC, identifying molecular biomarkers and pathways for risk stratification. Results: Among the 174 identified DEGs, the expression of genes associated with extracellular matrix (ECM)-receptor interaction pathway (ITGA5, ITGB1, LAMB1, and LAMC1) was increased in high-risk groups in both HPV-associated CC and HNC, while the expression of genes associated with T-cell immunity (CD3D, CD3E, CD8B, LCK, and ZAP70) was decreased and vice versa. The individual genes showed significant prognostic impact on HPV-associated cancers but not on HPV-negative cancers. The expression levels of identified genes were similar between HPV-negative and HPV-associated high-risk groups with distinct expression patterns only in HPV-associated low-risk groups. Each group of genes showed negative correlations and distinct patterns of immune cell infiltration in tumor microenvironments. Conclusions: These results allowed us to identify molecular biomarkers and pathways for risk stratification in HPV-associated cancers regardless of anatomical location. The identified targets were found to be selectively working in only HPV-associated cancers and not in HPV-negative cancers, indicating the possibility of selective targets governing HPV-infective tumor microenvironments.

Possibilities of skin coat color‐dependent risks and risk factors of squamous cell carcinoma and deafness of domestic cats inferred via RNA‐seq data

“…HPV infection is implicated in the development of human squamous cell carcinoma and cervical cancer (Augustin et al, 2020; Bao et al, 2021; Chrysovergis et al, 2021; Hennessey et al, 2009; Husain & Neyaz, 2017; Karina, 2022; Kwon et al, 2022; Teh & Krockenberger, 2021). Feline papillomavirus (FPV) type‐2 has been proposed as the primary cause of squamous cell carcinoma in domestic cats (Altamura et al, 2022; Carrai et al, 2020; Munday & Aberdein, 2012; Munday et al, 2008; Munday et al, 2011; Munday et al, 2017; O'Neill et al, 2011; Teh & Krockenberger, 2021; Thomson et al, 2016; Yamashita‐Kawanishi et al, 2021).…”

Possibilities of skin coat color-dependent risks and risk factors of squamous cell carcinoma and deafness of domestic cats inferred via RNA-seq data

“…The analysis identified the following pathways related to squamous cell carcinoma in which significantly larger number of SCDEGs were involved. Pathways in cancer (FDR ∼ 3.58×10 -3 ) The p53 signaling pathway (FDR ∼ 0.013×10 -2 ) Human papillomavirus (HPV) infection (FDR ∼ 8.33 × 10 -2 ) HPV infection is implicated in the development of human squamous cell carcinoma and cervical cancer (Hennessey et al, 2009; Husain et al, 2017; Augustin et al, 2020; Bao et al, 2021; Chrysovergis et al, 2021; The et al, 2021; Karina, 2022; Kwon et al, 2022). Feline papillomavirus (FPV) type-2 has been proposed as the primary cause of squamous cell carcinoma in domestic cats (Munday et al, 2008; Munday et al, 2011; O’Neill et al, 2011; Munday et al, 2012; Thomson et al, 2016; Munday et al, 2017; Carrai et al, 2020; Yamashita-Kawanishi et al, 2021; Teh et al, 2021; Altamura et al, 2022).…”

Implications of oral dysbiosis and HPV infection in head and neck cancer: from molecular and cellular mechanisms to early diagnosis and therapy

“…Genes associated with T lymphocyte function, CD3D (CD3 delta subunit of T-cell receptor complex), CD3E (CD3 epsilon subunit of T-cell receptor complex), CD8B (CD8 beta subunit), LCK (LCK proto-oncogene, SRC family tyrosine kinase), and ZAP70 (zeta chain of T-cell receptor-associated protein kinase 70kDa), are underexpressed in HPV-positive HNCs and cervical cancers. The observed dysregulation in the latter set of genes in both cancers indicates some expression specificity related to HPV infection, showing a significant prognostic impact on HPV-associated cancers ( 131 ).…”