Abstract

Natural killer/T cell lymphoma (NKTCL) most frequently affects the nasal cavity and upper aerodigestive tract (UAT) and is often mistaken for reactive disease processes, such as chronic rhinosinusitis (CRS). Recently, alterations of the nasal resident microbiota have been found in CRS. However, nasal microbial features in NKTCL have never been reported. This case-control study collected 46 NKTCL patients, 25 CRS patients and 24 matched healthy controls (HCs) to analyze nasal microbial profiles via 16S rRNA sequencing technology to improve our understanding of changes in the nasal microbiota in NKTCL. We found that alpha diversity was significantly decreased, while beta diversity was significantly increased in NKTCL compared with those in CRS and HCs. The genus Corynebacterium was significantly depleted in CRS and NKTCL versus that in HCs, while genus Staphylococcus was the most abundant in the NKTCL compared to that in the other two groups. The nasal microbial community was significantly different between UAT-NKTCL and non-UAT NKTCL patients. Importantly, based on a panel of taxa, excellent classification power with an AUC of 0.875 between UAT-NKTCL and CRS was achieved. Furthermore, the alpha diversity of the nasal microbiota was associated with several clinical covariates of NKTCL. Finally, PICRUSt analysis implicated an array of distinct functions in NKTCL that might be involved in the pathogenesis of the disease. In conclusion, the nasal microbial profile was unique in NKTCL. The nose-microbiota-UAT NKTCL axis represents a panel of promising biomarkers for clinical practice and contributes to revealing the potential pathogenesis of this malignancy.

Highlights

  • Natural killer/T cell lymphoma (NKTCL) is a rare lymphoma subtype of peripheral T/NK-cell lymphoma that generally exhibits aggressive behavior and poor prognosis, with an elevated prevalence in Asia and South America (Aozasa et al, 2008; Haverkos et al, 2016)

  • Rarefaction analysis showed that the observed species basically approached saturation in each sample, which suggested that the sequencing data were sufficient, with very few new species undetected (Figure 1A)

  • A Venn diagram exhibiting the overlaps between groups indicated that 314 of the total 2105 operational taxonomic units (OTUs) were unique to NKTCL, and 1248 of 1999 OTUs were shared between the chronic rhinosinusitis (CRS) and NKT groups, while 992 of 2105 OTUs were shared among the three groups (Figure 1B)

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Summary

Introduction

Natural killer/T cell lymphoma (NKTCL) is a rare lymphoma subtype of peripheral T/NK-cell lymphoma that generally exhibits aggressive behavior and poor prognosis, with an elevated prevalence in Asia and South America (Aozasa et al, 2008; Haverkos et al, 2016). NKTCL constitutes a distinct category of systemic malignancy, it presents predominantly as a localized tumor of the upper aerodigestive tract (UAT), involving the nasal cavity and adjacent sites, with topical aggressive destruction (Liu et al, 2014). Tumors presenting outside the UAT whereas share identical histologic characteristics with UAT disease have been classified as non-upper aerodigestive tract (NUAT) NKTCL, which has variable manifestations depending on the main site of involvement and typically exhibits a highly aggressive course (Au et al, 2009). The human nasal cavity is inhabited by a complex bacterial community which is mainly stable at the genus level, and bacterial colonization of the upper airways is a prerequisite for subsequent invasive disease (De Boeck et al, 2019). Alterations of the microbial communities that lead to detrimental effects on the host, has been proposed to contribute to the genesis of several diseases of the lymphohematopoietic system, including

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