Distinguishable Prognostic miRNA Signatures of Head and Neck Squamous Cell Cancer With or Without HPV Infection

Abstract

Since their discovery in the 1990’s, microRNAs (miRNA) have opened up new vistas in the field of cancer biology and are found to have fundamental roles in tumorigenesis and progression. As head and neck squamous cell carcinoma (HNSCC) with positive human papillomavirus (HPV+) is significantly distinct from its HPV negative (HPV−) counterpart in terms of both molecular mechanisms and clinical prognosis, the current study aimed to separately develop miRNA signatures for HPV+ and HPV− HNSCC as well as to explore the potential functions. Both signatures were reliable for the prediction of prognosis in their respective groups. Then Enrichment analysis was performed to predict the potential biological functions of the signatures. Importantly, combining previous studies and our results, we speculated that HPV+ HNSCC patients with low signature score had better immunity against the tumors and enhanced the sensitivity of therapies leading to improved prognosis, while HPV− HNSCC patients with high signature score acquired resistance to therapeutic approaches as well as dysregulation of cell metabolism leading to poor prognosis. Hence, we believe that the identified signatures respectively for HPV+ and HPV− HNSCC, are of great significance in accessing patient outcomes as well as uncovering new biomarkers and therapeutic targets, which are worth further investigation through molecular biology experiments.

Head and Neck Cancers Are Not Alike When Tarred with the Same Brush: An Epigenetic Perspective from the Cancerization Field to Prognosis

“…Not only the methylation of other genes and other genomic regions, but also other players, including noncoding RNAs and chromatin remodelers, should be explored. For example, global hypomethylation, associated with poor prognosis in other cancer types [189,[309][310][311], seems to differ according to HPV status and could help explain the prognosis differences observed. Furthermore, mutations in the histone methyltransferases NSD1 and NSD2 define a group of good prognosis among LSCC patients, but not in other HNSCC subtypes [312]…”

“…Nonetheless, miRNA signatures according to HPV status were reported in HNSCC. By comparing HPV-positive and HPV-negative tumors with adjacent tissue, 282 and 289 differentially expressed miR-NAs were identified, respectively [189]. Although these numbers were similar, when specific survival-associated miRNAs were evaluated, the expression of 39 miRNAs was associated with prognosis among HPV-positive patients, 16 among HPV-negative patients, and no miRNA was shared.…”

Micro-RNAs, the Cornerstones of the Future of Radiobiology in Head and Neck Cancers?

“…Analyzing data obtained from 515 HNSCC samples and 44 normal tissues, Luo et al highlights deregulated miRNAs for both positive and negative HPV HNSCC cases [ 96 ]. In the patient lot including 97 HPV + patients, 282 miRNAs were identified and after statistical analysis, a 7 miRNA signature was considered proper for its prognostic value.…”

“…Cases of HPV− with a high risk of miRNAs could benefit more from target therapies and HPV+ patients with a low risk of miRNAs could benefit more from immunotherapy. The authors mention metabolic disorder as a possible cause of therapeutic failure in HPV− patients with an increased miRNA risk score [ 66 , 67 , 96 ].…”

Shooting at Moving and Hidden Targets—Tumour Cell Plasticity and the Notch Signalling Pathway in Head and Neck Squamous Cell Carcinomas

“…They showed that immune-related pathways in HPV + tumours were mainly associated with low-risk scores. HPV − tumours, with characteristic high-risk scores, showed instead upregulation of metabolic and other vital oncogenic pathways [ 28 ]. It has further been shown that targeting the HPV16/18 viral oncogenes or neoantigens E6 and E7 by immunotherapy in HPV + tumours generated durable immune responses in the tumours, adding these proteins to the list of most promising targets in HNSCC.…”