Abstract
BackgroundMicrobial dysbiosis and microbiome-induced inflammation have emerged as important factors in oral squamous cell carcinoma (OSCC) tumorigenesis during the last two decades. However, the “rare biosphere” of the oral microbiome, including fungi, has been sparsely investigated. This study aimed to characterize the salivary mycobiome in a prospective Sudanese cohort of OSCC patients and to explore patterns of diversities associated with overall survival (OS).Materials and MethodsUnstimulated saliva samples (n = 72) were collected from patients diagnosed with OSCC (n = 59) and from non-OSCC control volunteers (n = 13). DNA was extracted using a combined enzymatic–mechanical extraction protocol. The salivary mycobiome was assessed using a next-generation sequencing (NGS)-based methodology by amplifying the ITS2 region. The impact of the abundance of different fungal genera on the survival of OSCC patients was analyzed using Kaplan–Meier and Cox regression survival analyses (SPPS).ResultsSixteen genera were identified exclusively in the saliva of OSCC patients. Candida, Malassezia, Saccharomyces, Aspergillus, and Cyberlindnera were the most relatively abundant fungal genera in both groups and showed higher abundance in OSCC patients. Kaplan–Meier survival analysis showed higher salivary carriage of the Candida genus significantly associated with poor OS of OSCC patients (Breslow test: p = 0.043). In contrast, the higher salivary carriage of Malassezia showed a significant association with favorable OS in OSCC patients (Breslow test: p = 0.039). The Cox proportional hazards multiple regression model was applied to adjust the salivary carriage of both Candida and Malassezia according to age (p = 0.029) and identified the genus Malassezia as an independent predictor of OS (hazard ratio = 0.383, 95% CI = 0.16–0.93, p = 0.03).ConclusionThe fungal compositional patterns in saliva from OSCC patients were different from those of individuals without OSCC. The fungal genus Malassezia was identified as a putative prognostic biomarker and therapeutic target for OSCC.
Highlights
The oral cavity is a habitat for a diverse and fluctuating collection of microorganisms (Aas et al, 2005; Nasidze et al, 2009; Yang et al, 2016)
This study aimed to investigate the salivary mycobiome in a cohort of oral squamous cell carcinoma (OSCC) patients and in non-OSCC controls from Sudan and its possible impact on clinical variables, including overall survival (OS)
The baseline mycobiome profiles utilizing nextgeneration sequencing (NGS) have been established for some time (Ghannoum et al, 2010; Mukherjee et al, 2014; Chandra et al, 2016), studies on the mycobiome in disease and health are scarce, and the actual contribution of the mycobiota in carcinogenesis has only recently been explored
Summary
The oral cavity is a habitat for a diverse and fluctuating collection of microorganisms (Aas et al, 2005; Nasidze et al, 2009; Yang et al, 2016). The oral microbiome, which includes, in addition to complex bacterial communities, oral fungi, viruses, and phages (Baker et al, 2017), is one of the most diverse microbial communities in the human body (Dewhirst et al, 2010; Huttenhower et al, 2012), and this is related to its multiple ecosystems (Arweiler et al, 2016). Recent advances in microbial detection techniques allowed the transition from culture-dependent studies of a single species to complex in vitro multispecies community detection and characterization studies (Baker et al, 2017). This study aimed to characterize the salivary mycobiome in a prospective Sudanese cohort of OSCC patients and to explore patterns of diversities associated with overall survival (OS)
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