Integrative Genomics and Transcriptomics Analysis Reveals Potential Mechanisms for Favorable Prognosis of Patients with HPV-Positive Head and Neck Carcinomas

Abstract

Patients with HPV-positive head neck squamous cell carcinomas (HNSCC) usually have a better prognosis than the HPV-negative cases while the underlying mechanism remains far from being well understood. We investigated this issue by an integrative analysis of clinically-annotated multi-omics HNSCC data released by the Cancer Genome Atlas. As confirmatory results, we found: (1) Co-occurrence of mutant TP53 and HPV infection was rare; (2) Regardless of HPV status, HNSCCs of wild-type TP53 implied a good survival chance for patients and had fewer genome-wide somatic mutations than those with a mutation burden on the gene. Our analysis further led to some novel observations. They included: (1) The genes involved in “DNA mismatch repair” pathway were up-regulated in HPV-positive tumors compared to normal tissue samples and HPV-negative cases, and thus constituted a strong predictive signature for the identification of HPV infection; (2) HPV infection could disrupt some regulatory miRNA-mRNA correlations operational in the HPV-negative tumors. In light of these results, we proposed a hypothesis for the favorable clinical outcomes of HPV-positive HNSCC patients. That is, the replication of HPV genome and/or its invasion into the genomes of cancer cells may enhance DNA repair mechanisms, which in turn limit the accumulation of lethal somatic mutations.

Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma

“…Studies implementing and exploring integrative approaches have unveiled therapy candidates in many tumors 26 , 28 . Nevertheless, molecular mechanisms underlying penile cancer remain poorly understood.…”

“…More recently, by assessing 23 PeCa patients we identified a high sensitivity and specificity of PPARG , MMP1 and MMP12 and hsa-miR-31-5p, hsa-miR-223-3p and hsa-miR-224-5p to distinguish penile tumors from normal tissue 22 . Next generation sequencing studies in penile carcinomas revealed the involvement of well-described genes, such as EGFR , PIK3CA , TP53 and CCND1 23 – 25 and dysregulated miRNAs 26 , all associated with cancer signaling pathways.…”

Somatic Host Cell Alterations in HPV Carcinogenesis

“…Head and neck cancers with wild-type TP53 have a better prognosis than those with TP53 mutations [ 2 , 83 ]. HPV positivity and p16 INK4A expression, which are both related to retention of wild type TP53 , are also positively correlated with overall 3-year survival in anal cancers [ 84 ].…”

Transcriptomics and Epigenomics in head and neck cancer: available repositories and molecular signatures

“…Another point of emphasis derived from the present overview is the growing integration among omics data obtained on the same cohort of patients. Even if these experiences are still limited for HNSCC and in terms of types of omics employed and amount of published studies [23,27,43,58,66,76], these initiatives enabling to better dissect cancer complexity deserve further investigations. Moreover, we can expect that new approaches based on artificial intelligence will be available in the next future dealing with more complex data even integrating multi-omics layers [94].…”