Clinical Significance of CUB and Sushi Multiple Domains 1 Inactivation in Head and Neck Squamous Cell Carcinoma.

Ah Jung,Kee Kwon,Joo Noh,Young-Gyu Eun,Young Lee

doi:10.3390/ijms19123996

Abstract

Although the genetic alteration of CUB and Sushi multiple domains 1 (CSMD1) is known to be associated with poor prognosis in several cancers, there is a lack of clinical relevance in head and neck cancer. The aim of this study was to offer insight into the clinical significance of CSMD1, utilizing a multimodal approach that leverages publicly available independent genome-wide expression datasets. CSMD1-related genes were found and analyzed to examine the clinical significance of CSMD1 inactivation in the HNSCC cohort of publicly available databases. We analyzed the frequency of somatic mutations, clinicopathologic characteristics, association with immunotherapy-related gene signatures, and the pathways of gene signatures. We found 363 CSMD1-related genes. The prognosis of the CSMD1-inactivated subgroup was poor. FBXW7, HLA-A, MED1, NOTCH2, NOTCH3, and TP53 had higher mutation rates in the CSMD1-inactivated subgroups. The Interferon-gamma score and immune signature score were elevated in CSMD1-inactivated subgroups. We identified several CSMD1-related pathways, such as the phosphatidylinositol signaling system and inositol phosphate metabolism. Our study using three large and independent datasets suggests that CSMD1-related gene signatures are associated with the prognosis of HNSCC patients.

Highlights

Head and neck squamous cell carcinoma (HNSCC) arises from mucosa lining the paranasal sinuses, nasal cavities, oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx [1]
We sought to find genes involved in the inactivation of CUB and Sushi multiple domains 1 (CSMD1)
We identified genes whose expression is correlated with mRNA expression of CSMD1 in the training cohort (TCGA cohort) (p < 0.001 and Pearson correlation coefficient >0.4 or

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) arises from mucosa lining the paranasal sinuses, nasal cavities, oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx [1]. Since there is considerable clinicopathological heterogeneity among the tumors, a deeper understanding of pathogenesis of HNSCC is needed. CUB and Sushi multiple domains 1 (CSMD1) is a large (~390 kDa) membrane-bound complement inhibitor [3]. It is composed of N-terminal CUB domains separated by single complement control protein (CCP) domains and followed by consecutive CCP domains. It has a single membrane-spanning domain at the C-terminus and a small cytoplasmic tail of 56 amino acids with a putative tyrosine phosphorylation site. A weaker expression was seen in breast, placenta and thyroid gland [3]

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