Human papillomavirus‐stratified analysis of the prognostic role of miR‐21 in oral cavity and oropharyngeal squamous cell carcinoma

Abstract

Human papillomavirus (HPV) infection plays a significant role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Expression of miR-21 has a prognostic role in a wide variety of cancers. The upregulation of miR-21 suppresses a number of target genes, including phosphatase tensin homologue (PTEN) and programmed cell death 4 (PDCD4). We investigated the association between the expression of miR-21 and the clinical features of HNSCC using stratified analysis based on HPV infection status. HPV status and miR-21 expression in HNSCC tissues from 167 patients were evaluated using in situ hybridization. The expression of PDCD4 and PTEN was examined by immunohistochemistry. The up-regulation of stromal miR-21 expression occurred in 40.6% of HPV-negative samples and 28.3% of the HPV-positive group. In HPV-stratified multivariate analysis, high miR-21 expression was associated with poor cancer-specific survival in HPV-negative tumors, but not in HPV-positive tumors. There was a significant association between miR-21 and cytoplasmic PDCD4 overexpression in HPV-negative HNSCCs. We suggest that stromal miR-21 expression is an independent prognostic factor in HPV-negative tumors and miR-21 may play different roles depending on HPV infection status.

Comparison of the miRNA expression profiles in fresh frozen and formalin-fixed paraffin-embedded tonsillar tumors

“…Furthermore, miR-9 has been shown to be activated by HPV leading to increased cell motility [53] and to be involved in the pathways regulating metastasis [54]. Upregulated miR-31, miR-221, and miR-21 were selected for confirmation from the group of miRNAs specific for HPV-independent tumors including HNC as playing a role in increasing cell proliferation, invasion, and migration [55–58], participating in regulation of epithelial-mesenchymal transition (EMT), or having a prognostic impact [59, 60]. Further choices were miR-34a, specific for HPV-negative tumors, a tumor suppressor whose downregulation has been shown in a number of tumor types including HNC [61, 62], as well as miR-16, the inhibition of which promotes cell proliferation, migration, invasion, and EMT and contributes to tumor progression [63].…”

Prognostic Value of MiR-21: An Updated Meta-Analysis in Head and Neck Squamous Cell Carcinoma (HNSCC)

“…Figure 2 describes the forest plot for miR-21 with the hazard ratio for each study included in the meta-analysis. As shown, from a total of seven studies included in the analysis, five revealed significant hazard ratios [22][23][24][25][26] indicating high expressions of miR-21 associated with poor survival, while two studies obtained nonsignificant hazard ratios [21,27]. The overall corrected hazard ratio is HR = 1.719, 95% CI = (1.402, 2.109) and statistically significant (Z = 5.198, p < 0.001), indicating that a high expression of miR-21 is associated with poor survival for patients diagnosed with HNSCC.…”

“…Eventually, we removed 11 more articles, as survival analyses was not reported as HR and 95% CI. The current meta-analysis collected seven articles that investigated the prognostic value of miR-21 in head and neck cancers [21][22][23][24][25][26][27].…”

Visualization of mucosal field in HPV positive and negative oropharyngeal squamous cell carcinomas: combined genomic and radiology based 3D model

“…www.nature.com/scientificreports www.nature.com/scientificreports/ We found miR-21-5p expression to reach higher levels in HPV positive tumors and 1 cm distant peritumoral area. In study evidences published so far, miR-21 showed significantly lower expression in HPV positive head and neck tumors, compared to HPV negative ones [36][37][38] . However, these studies lacked the clinical and histopathological homogeneity of their samples.…”