Dataset Information

Plasma Protein Levels Analysis in Multiple Sclerosis Sardinian Families Identified C9 and CYP24A1 as Candidate Biomarkers.

ABSTRACT: Here we investigate protein levels in 69 multiple sclerosis (MS) cases and 143 healthy controls (HC) from twenty Sardinian families to search for promising biomarkers in plasma. Using antibody suspension bead array technology, the plasma levels of 56 MS-related proteins were obtained. Differences between MS cases and HC were estimated using Linear Mixed Models or Linear Quantile Mixed Models. The proportion of proteins level variability, explained by a set of 119 MS-risk SNPs as to the literature, was also quantified. Higher plasma C9 and CYP24A1 levels were found in MS cases compared to HC (p < 0.05 after Holm multiple testing correction), with protein level differences estimated as, respectively, 0.53 (95% CI: 0.25, 0.81) and 0.42 (95% CI: 0.19, 0.65) times plasma level standard deviation measured in HC. Furthermore, C9 resulted in both statistically significantly higher relapsing-remitting MS (RRMS) and secondary-progressive MS (SPMS) compared to HC, with SPMS showing the highest differences. Instead, CYP24A1 was statistically significantly higher only in RRMS as compared to HC. Respectively, 26% (95% CI: 10%, 44%) and 16% (95% CI: 9%, 39%) of CYP24A1 and C9 plasma level variability was explained by known MS-risk SNPs. Our results highlight C9 and CYP24A1 as potential biomarkers in plasma for MS and allow us to gain insight into molecular disease mechanisms.

SUBMITTER: Nova A

PROVIDER: S-EPMC8879906 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Plasma Protein Levels Analysis in Multiple Sclerosis Sardinian Families Identified C9 and CYP24A1 as Candidate Biomarkers.

Nova Andrea A Fazia Teresa T Beecham Ashley A Saddi Valeria V Piras Marialuisa M McCauley Jacob L JL Berzuini Carlo C Bernardinelli Luisa L

Life (Basel, Switzerland) 20220120 2

Here we investigate protein levels in 69 multiple sclerosis (MS) cases and 143 healthy controls (HC) from twenty Sardinian families to search for promising biomarkers in plasma. Using antibody suspension bead array technology, the plasma levels of 56 MS-related proteins were obtained. Differences between MS cases and HC were estimated using Linear Mixed Models or Linear Quantile Mixed Models. The proportion of proteins level variability, explained by a set of 119 MS-risk SNPs as to the literatur ...[more]

PMID: 35207439

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Project description:DNA hypermethylation is a common epigenetic abnormality in colorectal cancers (CRCs) and a promising class of CRC screening biomarkers. We conducted a genome-wide search for novel neoplasia-specific hypermethylation events in the colon. We applied methylation microarray analysis to identify loci hypermethylated in 17 primary CRCs relative to eight non-neoplastic colonic mucosae (NCs) from neoplasia-free subjects. These CRC-associated hypermethylation events were then individually evaluated for their ability to discriminate neoplastic from non-neoplastic cases, based on real-time quantitative methylation-specific PCR (qMSP) assays in 113 colonic tissues: 51 CRCs, nine adenomas, 19 NCs from CRC patients (CRC-NCs), and 34 NCs from neoplasia-free subjects (control NCs). A strict microarray data filtering identified 169 candidate CRC-associated hypermethylation events. Fourteen of these 169 loci were evaluated using qMSP assays. Ten of these 14 methylation events significantly distinguished CRCs from age-matched control NCs (P<0.05 by receiver operator characteristic curve analysis); methylation of visual system homeobox 2 (VSX2) achieved the highest discriminative accuracy (83.3% sensitivity and 92.3% specificity, P<1×10(-6)), followed by BEN domain containing 4 (BEND4), neuronal pentraxin I (NPTX1), ALX homeobox 3 (ALX3), miR-34b, glucagon-like peptide 1 receptor (GLP1R), BTG4, homer homolog 2 (HOMER2), zinc finger protein 583 (ZNF583), and gap junction protein, gamma 1 (GJC1). Adenomas were significantly discriminated from control NCs by hypermethylation of VSX2, BEND4, NPTX1, miR-34b, GLP1R, and HOMER2 (P<0.05). CRC-NCs were significantly distinguished from control NCs by methylation of ALX3 (P<1×10(-4)). In conclusion, systematic methylome-wide analysis has identified ten novel methylation events in neoplastic and non-neoplastic colonic mucosae from CRC patients. These potential biomarkers significantly discriminate CRC patients from controls. Thus, they merit further evaluation in stool- and circulating DNA-based CRC detection studies.

Dataset Information

Plasma Protein Levels Analysis in Multiple Sclerosis Sardinian Families Identified C9 and CYP24A1 as Candidate Biomarkers.

Publications

Plasma Protein Levels Analysis in Multiple Sclerosis Sardinian Families Identified C9 and CYP24A1 as Candidate Biomarkers.

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