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

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.

Deregulation of CSMD1 targeted by microRNA-10b drives gastric cancer progression through the NF-κB pathway

“…Multiple mechanisms can reduce the expression of CSMD1. The allelic loss, mutation and methylation of CSMD1 have been detected in breast cancer, head and neck cancer, oral squamous cell carcinoma, prostate cancer, rectum, liver, lung and skin cancer and many other malignant tumors such as breast cancer, head and neck cancer, oral squamous cell carcinoma, prostate, colorectal cancer, liver cancer, lung cancer and skin cancer, etc [5,6,[8][9][10][11][12][13][14][15][16]. Using four databases of TargetScan, Miranda, miRWalk and PicTar, highly conserved microRNA-10b binding sites were found in CSMD1 3′-UTRs.…”

“…Hunman CUB and sushi multiple domains protein 1 (CSMD1) is a novel candidate tumor suppressor gene located on the p arm of chromosome 8 (8p23) [4]. Previous studies have shown that the deletion of 8p23.2 or reduced expression of CSMD1 has something to do with poor prognosis in many cancers [5][6][7][8][9]. Multiple mechanisms can reduce the expression of CSMD1.…”

“…Multiple mechanisms can reduce the expression of CSMD1. The allelic loss, copy number aberrations, mutations, and methylations of CSMD1 have been detected in various malignant tumours such as head and neck tumor, colorectal cancers, liver cancer, and so on [5][6][7][8][9][10][11][12][13][14][15][16]. Besides, it has been proved that the change of microRNA expression and dysfunction play an important role in tumorigenesis and metastasis by regulating target genes and pathways, subsequently resulting in the alteration of proliferation, differentiation, apoptosis, invasion and metastasis of tumor cells [17][18][19].…”

Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic Allografts

“…While UNC13C and STEAP4 mutations have been found human head and neck cancers, their role in oral carcinogenesis remains unclear. Similarly, deletion of CSMD1 gene has been associated with lymph node metastasis and poor prognosis in several cancers and is seen commonly in smokers [35]. We detected the less common NOTCH2 mutation in RP-MOC1 cells.…”

Peer Review #2 of "Whole genome sequencing analysis identifies recurrent structural alterations in esophageal squamous cell carcinoma (v0.1)"

“…Recurrent SVs in CSMD1, WWOX, ERC1, PDE4D and SHANK2 were also identified in five tumor samples. The CUB and Sushi multiple domains 1 (CSMD1) is a tumor suppressor gene reported to be associated with poor prognosis in many cancer types including breast cancer, gastric cancer, head and neck squamous cell carcinoma (HNSCC), and hepatocellular carcinoma (Deng et al, 2012) , (Zhang et al, 2019) , (Jung et al, 2018). Deletion of WWOX, a tumor suppressor gene, is frequent in esophageal adenocarcinoma (32%) and stomach adenocarcinoma (30.2%) and also observed in other human cancer types such as colon adenocarcinoma, bladder urothelial carcinoma and lung adenocarcinoma (Hussain et al, 2019).…”