The Mucin Family of Proteins: Candidates as Potential Biomarkers for Colon Cancer

Cox, Kristin E.; Liu, Shanglei; Lwin, Thinzar M.; Hoffman, Robert M.; Batra, Surinder K.; Bouvet, Michael

doi:10.3390/cancers15051491

Cited by 21 publications

(12 citation statements)

References 121 publications

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“…Although the set of CMR genes includes a wide variety of genetically diverse genes, several important polymorphic gene families are underrepresented in it. One such highly heterogeneous gene family is the mucin gene cluster ( MUC1 – MUC24 ) 40 . Mucin genes encode large glycoproteins that are essential to barrier maintenance and the defense of epithelial tissues.…”

Section: Resultsmentioning

confidence: 99%

Locityper: targeted genotyping of complex polymorphic genes

Prodanov,

Plender,

Seebohm

et al. 2024

Preprint

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The human genome contains numerous structurally-variable polymorphic loci, including several hundred disease-associated genes, almost inaccessible for accurate variant calling. Here we present Locityper, a tool capable of genotyping such challenging genes using short and long-read whole genome sequencing. For each target, Locityper recruits and aligns reads to locus haplotypes, for instance extracted from a pangenome, and finds the likeliest haplotype pair by optimizing read alignment, insert size and read depth profiles. Locityper accurately genotypes up to 194 of 256 challenging medically relevant loci (95% haplotypes at QV33), an 8.8-fold gain compared to 22 genes achieved with standard variant calling pipelines. Furthermore, Locityper provides access to hyperpolymorphic HLA genes and other gene families, including KIR, MUC and FCGR. With its low running time of 1h10m per sample at 8 threads, Locityper is scalable to biobank-sized cohorts, enabling association studies for previously intractable disease-relevant genes.

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Section: Resultsmentioning

confidence: 99%

Locityper: targeted genotyping of complex polymorphic genes

Prodanov,

Plender,

Seebohm

et al. 2024

Preprint

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“…Because there is a strong correlation between the types of mucins produced by the colon intestinal mucosa and the prognosis for cancer, as has been demonstrated in multiple studies (Cox et al, 2023;Hsu et al, 2017;Imai et al, 2013;Kasprzak et al, 2019;Lungulescu et al, 2017;Zhang et al, 2004), we performed a brief evaluation of neutral mucin produced in the colon mucosa of our groups by histochemistry using the periodic acid-Schiff method (PAS). Three semiseriated sections per rat were rehydrated, stained with hematoxylin for 2 min, washed in water, immersed in a 0.5% periodic acid solution for 15 min, and in a Schiff solution for 30 min.…”

Section: Histochemistry Proceduresmentioning

confidence: 99%

MT1‐MMP and TIMP‐2 are first expressed in the colon glands after a single dose of azoxymethane (AOM)

da Silva,

Freitas,

do Carmo

et al. 2023

The Anatomical Record

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Tissue inhibitor of metalloproteinase‐2 (TIMP‐2) and membrane‐type 1‐matrix metalloproteinase (MT1‐MMP) are always expressed during the cancer process. The aim was to identify which regions of the colon mucosa MT1‐MMP and TIMP‐2 begin to express themselves, as well as to establish their expression in relation to cell proliferation and mucin production. After intraperitoneal injection of 15 mg/kg of azoxymethane (AOM) at 4, 12, and 20 weeks, histological sections of the middle segment of the rat colon mucosa were evaluated by immunohistochemistry for cell proliferation and expression of MT1‐MMP and TIMP‐2 and histochemistry for mucin. As a result, a single dose of AOM initially increased the intensity of MT1‐MMP and TIMP‐2 expression in the conjunctive cells and glands, concurrently with alterations in the distribution of the mucin produced in the gland of the large intestine mucosa and cell proliferation. As a result, at 4 and 12 weeks, a single dose of AOM initially stimulated the expression of MT1‐MMP and TIMP‐2 in the conjunctive cells and glands with greater intensity. Changes in the cell proliferation and distribution of the mucin produced in the large intestine mucosa gland were observed. We conclude that MT1‐MMP and TIMP‐2 were first and strongly expressed in all cells of the colon glands, concurrently with an increase in cell proliferation and a diffuse dispersion of mucin, indicating the onset of the dysplasia process following a single dosage of AOM.

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“…The mucin family of glycoproteins contains twenty-four mucin proteins (MUC1–MUC24) which are involved in cell signaling and barrier protection [ 31 ]. Mucins have been shown to have diverse expression profiles among numerous organ systems and between normal vs. premalignant vs. malignant tissues within the colon [ 32 ]. MUC4 is known to be expressed within the normal colon [ 33 , 34 ], while MUC5AC is absent [ 35 , 36 , 37 ], making it a superior target for the detection of premalignant and malignant colonic tissues.…”

Section: Introductionmentioning

confidence: 99%

Specific Targeting and Labeling of Colonic Polyps in CPC-APC Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon Cancer

Turner

Cox

Liu

et al. 2023

CIMB

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Poor visualization of polyps can limit colorectal cancer screening. Fluorescent antibodies to mucin5AC (MUC5AC), a glycoprotein upregulated in adenomas and colorectal cancer, could improve screening colonoscopy polyp detection rate. Adenomatous polyposis coli flox mice with a Cdx2-Cre transgene (CPC-APC) develop colonic polyps that contain both dysplastic and malignant tissue. Mice received MUC5AC-IR800 or IRdye800 as a control IV and were sacrificed after 48 h for near-infrared imaging of their colons. A polyp-to-background ratio (PBR) was calculated for each polyp by dividing the mean fluorescence intensity of the polyp by the mean fluorescence intensity of the background tissue. The mean 25 μg PBR was 1.70 (±0.56); the mean 50 μg PBR was 2.64 (±0.97); the mean 100 μg PBR was 3.32 (±1.33); and the mean 150 μg PBR was 3.38 (±0.87). The mean PBR of the dye-only control was 2.22 (±1.02), significantly less than the 150 μg arm (p-value 0.008). The present study demonstrates the ability of fluorescent anti-MUC5AC antibodies to specifically target and label colonic polyps containing high-grade dysplasia and intramucosal adenocarcinoma in CPC-APC mice. This technology can potentially improve the detection rate and decrease the miss rate of advanced colonic neoplasia and early cancer at colonoscopy.

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The Mucin Family of Proteins: Candidates as Potential Biomarkers for Colon Cancer

Cited by 21 publications

References 121 publications

Locityper: targeted genotyping of complex polymorphic genes

Locityper: targeted genotyping of complex polymorphic genes

MT1‐MMP and TIMP‐2 are first expressed in the colon glands after a single dose of azoxymethane (AOM)

Specific Targeting and Labeling of Colonic Polyps in CPC-APC Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon Cancer

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