Metaproteomic Analysis of an Oral Squamous Cell Carcinoma Dataset Suggests Diagnostic Potential of the Mycobiome

Abstract

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, with an estimated 5-year survival rate of only 40–50%, largely due to late detection and diagnosis. Emerging evidence suggests that the human microbiome may be implicated in OSCC, with oral microbiome studies putatively identifying relevant bacterial species. As the impact of other microbial organisms, such as fungi and viruses, has largely been neglected, a bioinformatic approach utilizing the Trans-Proteomic Pipeline (TPP) and the R statistical programming language was implemented here to investigate not only bacteria, but also viruses and fungi in the context of a publicly available, OSCC, mass spectrometry (MS) dataset. Overall viral, bacterial, and fungal composition was inferred in control and OSCC patient tissue from protein data, with a range of proteins observed to be differentially enriched between healthy and OSCC conditions, of which the fungal protein profile presented as the best potential discriminator of OSCC within the analysed dataset. While the current project sheds new light on the fungal and viral spheres of the oral microbiome in cancer in silico, further research will be required to validate these findings in an experimental setting.

Oral microbiota and oral squamous cell carcinoma: a review of their relation and carcinogenic mechanisms

“…While the bacterial elements of the OSCC microbiome have been extensively studied, the fungal components remain relatively unexplored and poorly defined ( 99 ). The mycobiome is an essential part of the human microbiome; it is the collective genome of different fungus species.…”

Fungal footprints in oral cancer: unveiling the oral mycobiome

“…In a recent metaproteomic analysis, a total of 196 fungal proteins demonstrated significant changes in abundance across different forms of OSCC. Most of the detected fungi had not been thoroughly investigated, and researchers were unaware of their toxicity or lethal associations in the oral cavity of humans ( 50 ). However, other fungi, including Verruconis gallopava ( 77 ), Dimargaris cristalligena ( 78 , 79 ), and Syncephalastrum racemosum ( 80 ), were found to be more frequently present in OSCC lesions and linked to opportunistic infections.…”

Comprehensive Overview of Bottom-Up Proteomics Using Mass Spectrometry

“…Others have performed these tasks and include various analysis routines as addons such as TAILS Nterminomics analysis, 674 quantitation analysis with Py-Quant, 675 SimPhospho, 676 WinProphet, 677 ProtyQuant, 678 and inclusion of R-tools for metaproteomic analysis. 679 As a collection of individual tools, they are easily amenable to pipelining in a very flexible manner to support a huge variety of combinations and workflows, and a custom program may easily be inserted into the pipeline to support technology development.…”

“…From its inception, the TPP has been and will always be free and open-source software, allowing anyone to use it without cost and to inspect its source code, alter the source code for their own needs, or even incorporate parts of it into their own products. Others have performed these tasks and include various analysis routines as addons such as TAILS N-terminomics analysis, quantitation analysis with PyQuant, SimPhospho, WinProphet, ProtyQuant, and inclusion of R-tools for metaproteomic analysis . As a collection of individual tools, they are easily amenable to pipelining in a very flexible manner to support a huge variety of combinations and workflows, and a custom program may easily be inserted into the pipeline to support technology development.…”