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Plasma microRNA biomarker detection for mild cognitive impairment using differential correlation analysis

ABSTRACT: Background: Mild cognitive impairment (MCI) is an intermediate state between normal aging, and Alzheimer’s disease, and other dementias. Early detection of dementia, and MCI, is a crucial issue in terms of secondary prevention. Blood biomarker detection is a possible way for early detection of MCI. Although disease biomarkers are detected by, in general, using single molecular analysis such as t-test, another possible approach is based on interaction between molecules. Results: Differential correlation analysis, which detects difference on correlation of two variables in case/control study, was carried out to the dataset with 745 microRNAs (miRNAs) from plasma samples of 30 age-matched controls and 23 MCI patients in Japan. The 20 pairs of miRNAs, which consist of 20 miRNAs, were selected as MCI markers. Two pairs of miRNAs (hsa-miR-191 and hsa-miR-101, and hsa-miR-103 and hsa-miR-222) out of 20 attained the highest area under the curve (AUC) value of 0.962 for MCI detection. Other two miRNA pairs that include hsa-miR-191 and hsa-miR-125b also attained high AUC value of ≥ 0.95. Pathway analysis was performed to the MCI markers for further understanding of biological implications. As a result, collapsed correlation on hsa-miR-191 and emerged correlation on hsa-miR-125b may have key role in MCI, and dementia progression. Conclusion: Differential correlation analysis, a bioinformatics tool to elucidate complicated and interdependent biological systems behind diseases, detects effective MCI markers that cannot be found by single molecule analysis such as t-test.

ORGANISM(S): Homo sapiens

PROVIDER: GSE90828 | GEO | 2016/12/10

SECONDARY ACCESSION(S): PRJNA356063

REPOSITORIES: GEO

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Project description:Little is known about the alterations in microRNA (miRNA) expression patterns during the consecutive stages of cervical cancer development and their association with chromosomal instability and epigenetic changes. We integrated miRNA expression profiles in normal cervical squamous epithelium, high-grade precancerous lesions (CIN2-3), squamous cell carcinomas (SCC) and adenocarcinomas (AdCAs) with previously generated chromosomal profiles of the same samples. In addition, the DNA methylation status of downregulated miRNAs located in a CpG island was determined. Significantly differential expression during the consecutive stages of cervical SCC development was observed for 106 miRNAs. Altered expression of 5 significantly differentially expressed miRNAs, hsa-miR-9 (1q23.2), hsa-miR-15b (3q25.32), hsa-miR-28-5p (3q27.3), hsa-miR-100 and hsa-miR-125b (both 11q24.1) was directly linked to frequent chromosomal alterations. Another 9 significantly downregulated miRNAs were located within a CpG island. Three of these 9 miRNAs, hsa-miR-203, hsa-miR-572, and hsa-miR-638, showed increased methylation in cervical cancer cell lines and HPV-immortalised cells compared to primary keratinocytes. Functional analyses were performed for hsa-miR-9, representing a potential oncogene with increased expression linked to a chromosomal gain, and hsa-miR-203, representing a potential tumour suppressor gene silenced by DNA methylation. Hsa-miR-9 and hsa-miR-203 were found to alter cell viability and anchorage independent growth in vitro, respectively, supporting their oncogenic and tumour suppressive function in cervical cancer. In conclusion, differential expression of 106 miRNAs, partly associated with chromosomal alterations and epigenetic changes, was observed during cervical SCC development. Altered expression of hsa-miR-9 and hsa-miR-203 was shown to be functionally relevant, underlining the importance of deregulated miRNA expression in cervical carcinogenesis. 10 squamous cell carcinomas of the cervix, 9 adenocarcinomas of the cervix, 18 high-grade cervical intraepithelial neoplasias (CIN2-3), and 10 cervical squamous epithelial samples with normal histology were analysed using single channel (Cy3) miRNA microarrays from Agilent (G4471A-016436).

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Plasma microRNA biomarker detection for mild cognitive impairment using differential correlation analysis

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