Association of Inherited Copy Number Variation in ADAM3A and ADAM5 Pseudogenes with Oropharynx Cancer Risk and Outcome

Abstract

Inherited copy number variations (CNVs) can provide valuable information for cancer susceptibility and prognosis. However, their association with oropharynx squamous cell carcinoma (OPSCC) is still poorly studied. Using microarrays analysis, we identified three inherited CNVs associated with OPSCC risk, of which one was validated in 152 OPSCC patients and 155 controls and related to pseudogene-microRNA-mRNA interaction. Individuals with three or more copies of ADAM3A and ADAM5 pseudogenes (8p11.22 chromosome region) were under 6.49-fold increased risk of OPSCC. ADAM5 shared a highly homologous sequence with the ADAM9 3′-UTR, predicted to be a binding site for miR-122b-5p. Individuals carrying more than three copies of ADAM3A and ADAM5 presented higher ADAM9 expression levels. Moreover, patients with total deletion or one copy of pseudogenes and with higher expression of miR-122b-5p presented worse prognoses. Our data suggest, for the first time, that ADAM3A and ADAM5 pseudogene-inherited CNV could modulate OPSCC occurrence and prognosis, possibly through the interaction of ADAM5 pseudogene transcript, miR-122b-5p, and ADAM9.

Identifying the prognosis implication, immunotherapy response prediction value, and potential targeted compound inhibitors of integrin subunit α3 (ITGA3) in human cancers

“…TMB and MSI have emerged as major response-predictive biomarkers for the effectiveness of ICB therapy [ 24 , 25 ]. CNV, as a form of genomic structural variation, has been proven to be involved in the occurrence and development of various cancers and affects the prognosis of patients [ 37 , 38 ], and can also be used in cancer diagnosis [ 39 ]. As an epigenetic modification, DNA methylation often disrupts gene regulation and affects patient prognosis in a variety of cancers [ 40 , 41 ].…”

Pseudogenes in Cancer: State of the Art

“…In a study by Carron et al, an increased risk of developing oropharynx squamous cell carcinoma was associated with the presence of three or more copies of the pseudogenes ADAM3A and ADAM5 [ 58 ]. The authors also identified a highly homologous region in the 3′-UTR sequence of ADAM5 and ADAM9 that serves as a binding site for miR-122b-5p.…”

“…The authors also identified a highly homologous region in the 3′-UTR sequence of ADAM5 and ADAM9 that serves as a binding site for miR-122b-5p. The competition for this miRNA binding site between ADAM5 and ADAM9 suggests a potential mechanism for the coordination of their expression and the promotion of tumorigenesis [ 58 ].…”

The impact ofERP29on the progression of pharyngeal squamous cell carcinoma

“…Smoking and drinking chronic habits [2] and HPV infection [3] are known risk factors for developing the disease. Additionally, inherited and acquired genetic alterations play important roles in pharynx cancer risk and progression [4][5][6][7].…”