Genomic alterations in mucins across cancers

Abstract

The significance of mucins in cancers has led to the development of novel biomarkers and therapeutic agents against cancers. Despite significant advances in the understanding of mucins, systemic investigations into the role of mucins in cancer biology focusing particularly on the histological subtypes and stages, along with other variables, are yet to be carried out to discover potential novel functions and cancer-specific roles. Here, we investigated 11 mucin expressing cancers for DNA mutations, mRNA expression, copy number, methylation, and the impacts these genomic features may have on patient survival by utilizing The Cancer Genome Atlas dataset. We demonstrate that mucin DNA mutations have a significant rate, pattern, and impact on cancer patient survival depending on the tissue of origin. This includes a frequent T112P mutation in MUC1 that is seen in half of the pancreatic MUC1 mutations, as well as being present in other cancers. We also observed a very frequent MUC4 mutation at H4205, which correlated with survival outcomes in patients. Furthermore, we observed significant alterations in mucin mRNA expression in multiple tumor types. Our results demonstrate de novo expression of certain mucins in cancer tissues, including MUC21 in colorectal cancers. We observed a general decrease in promoter methylation for mucins, which correlated with decreased expression of many genes, such as MUC15 in kidney cancers. Lastly, several mucin gene loci demonstrated copy number increase in multiple histological subtypes. Thus, our study presents a comprehensive analysis of genomic alterations in mucins and their corresponding roles in cancer progression.

Dual prognostic role for 2-oxoglutarate oxygenases in ten diverse cancer types: Implications for cell cycle regulation and cell adhesion maintenance

“…Likewise, mucin MUC4 mutations improved survival in clear cell renal cancer patients (HR=0.57, P=0.012) (Table S3); an observation that is consistent with another study [22].…”

Comprehensive Characterization of RNA Editing in Primary Gastric Adenocarcinoma through RNA-seq Data Analysis

“…Normal gastric epithelial cells transcribe MUCs, which have several functions including; protection against mechanical and infectious lesions, lubrication and acid resistance [86]. Several studies have been reported that transcription pro le of mucins are changed in gastrointestinal cancers, which overall suggests an important role for MUCs in gastric cancer [87][88][89]. Our results reinforced the hypothesis that inappropriate RNA editing can be involved in gastric cancer development.…”

Phosphoinositide 3-Kinase Signaling Pathway in Pancreatic Ductal Adenocarcinoma Progression, Pathogenesis, and Therapeutics

“…Mucins, such as MUC4, have been demonstrated to be the targets of K-Ras G12D mutant, which is regulated by a transcriptional or post-transcriptional mechanisms (Vasseur et al, 2015 ). Furthermore, PI3K signaling is regulated by MUC1, a type I transmembrane glycoprotein that regulates aggressiveness in PDAC by inducing metabolic and signaling alterations (Chaika et al, 2012a ; Liu et al, 2014 ; Mehla and Singh, 2014 ; Gebregiworgis et al, 2017 ; King et al, 2017 ). MUC1 regulates the expression and signaling of multiple receptor tyrosine kinases, including PDGFR, EGFR, and c-Met that signals through the PI3K signaling cascade to drive cellular processes such as proliferation, migration, and survival (Singh and Hollingsworth, 2006 ; Singh et al, 2007 , 2008 ; Engel et al, 2016 ).…”