Dataset Information

Serum miR-21, miR-29a, and miR-125b Are Promising Biomarkers for the Early Detection of Colorectal Neoplasia.

ABSTRACT: Circulating microRNAs (miRNA) are emerging as promising diagnostic biomarkers for colorectal cancer, but their usefulness for detecting early colorectal neoplasms remains unclear. This study aimed to identify serum miRNA biomarkers for the identification of patients with early colorectal neoplasms.A cohort of 237 serum samples from 160 patients with early colorectal neoplasms (148 precancerous lesions and 12 cancers) and 77 healthy subjects was analyzed in a three-step approach that included a comprehensive literature review for published biomarkers, a screening phase, and a validation phase. RNA was extracted from sera, and levels of miRNAs were examined by real-time RT-PCR.Nine miRNAs (miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-24, miR-29a, miR-92, and miR-125b) were selected as candidate biomarkers for initial analysis. In the screening phase, serum levels of miR-21, miR-29a, and miR-125b were significantly higher in patients with early colorectal neoplasm than in healthy controls. Elevated levels of miR-21, miR-29a, and miR-125b were confirmed in the validation phase using an independent set of subjects. Area under the curve (AUC) values for serum miR-21, miR-29a, miR-125b, and their combined score in discriminating patients with early colorectal neoplasm from healthy controls were 0.706, 0.741, 0.806, and 0.827, respectively. Serum levels of miR-29a and miR-125b were significantly higher in patients who had only small colorectal neoplasms (?5 mm) than in healthy subjects.Because serum levels of miR-21, miR-29a, and miR-125b discriminated patients with early colorectal neoplasm from healthy controls, our data highlight the potential clinical use of these molecular signatures for noninvasive screening of patients with colorectal neoplasia.

SUBMITTER: Yamada A

PROVIDER: S-EPMC4573815 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Serum miR-21, miR-29a, and miR-125b Are Promising Biomarkers for the Early Detection of Colorectal Neoplasia.

Yamada Atsushi A Horimatsu Takahiro T Okugawa Yoshinaga Y Nishida Naoshi N Honjo Hajime H Ida Hiroshi H Kou Tadayuki T Kusaka Toshihiro T Sasaki Yu Y Yagi Makato M Higurashi Takuma T Yukawa Norio N Amanuma Yusuke Y Kikuchi Osamu O Muto Manabu M Ueno Yoshiyuki Y Nakajima Atsushi A Chiba Tsutomu T Boland C Richard CR Goel Ajay A

Clinical cancer research : an official journal of the American Association for Cancer Research 20150602 18

<h4>Purpose</h4>Circulating microRNAs (miRNA) are emerging as promising diagnostic biomarkers for colorectal cancer, but their usefulness for detecting early colorectal neoplasms remains unclear. This study aimed to identify serum miRNA biomarkers for the identification of patients with early colorectal neoplasms.<h4>Experimental design</h4>A cohort of 237 serum samples from 160 patients with early colorectal neoplasms (148 precancerous lesions and 12 cancers) and 77 healthy subjects was analyze ...[more]

PMID: 26038573

Similar Datasets

Project description:BackgroundEarly detection of colorectal neoplasms, including colorectal cancers (CRCs) and advanced colorectal adenomas (AAs), is crucial to improve patient survival. Circulating microRNAs (miRNAs) in peripheral blood are emerging as noninvasive diagnostic markers for multiple cancers, but their potential for screening colorectal neoplasms remains ambiguous.AimTo identify candidate circulating cell-free miRNAs as diagnostic biomarkers in patients with colorectal neoplasms.MethodsThe study was divided into three phases: (1) Candidate miRNAs were selected from three public miRNA datasets using differential gene expression analysis methods; (2) an independent set of serum samples from 60 CRC patients, 60 AA patients and 30 healthy controls (HCs) was included and analyzed by quantitative real-time polymerase chain reaction for miRNAs, and their diagnostic power was detected by receiver operating characteristic (ROC) analysis; and (3) the origin and function of miRNAs in cancer patients were investigated in cancer cell lines and tumor tissues.ResultsBased on bioinformatics analysis, miR-627-5p and miR-199a-5p were differentially expressed in both the serum and tissues of patients with colorectal neoplasms and HCs and were selected for further study. Further validation in an independent cohort revealed that both circulating miR-627-5p and miR-199a-5p were sequentially increased from HCs and AAs to CRCs. The diagnostic power of miR-672-5p yielded an area under the curve (AUC) value of 0.90, and miR-199a-5p had an AUC of 0.83 in discriminating colorectal neoplasms from HCs. A logistic integrated model combining miR-199a-5p and miR-627-5p exhibited a higher diagnostic performance than either miRNA. Additionally, the levels of serum miR-627-5p and miR-199a-5p in CRC patients were significantly lower after surgery than before surgery and the expression of both miRNAs was increased with culture time in the culture media of several CRC cell lines, suggesting that the upregulated serum expression of both miRNAs in CRC might be tumor derived. Furthermore, in vitro experiments revealed that miR-627-5p and miR-199a-5p acted as tumor suppressors in CRC cells.ConclusionSerum levels of miR-199a-5p and miR-627-5p were markedly increased in patients with colorectal neoplasms and showed strong potential as minimally invasive biomarkers for the early screening of colorectal neoplasms.

Project description:BackgroundPatient participation in colorectal cancer (CRC) screening via a stool test and colonoscopy is suboptimal, but participation can be improved by the development of a blood test. However, the suboptimal detection abilities of blood tests for advanced neoplasia, including advanced adenoma (AA) and CRC, limit their application. We aimed to investigate the proteomic landscape of small extracellular vesicles (sEVs) from the serum of patients with colorectal neoplasia and identify specific sEV proteins that could serve as biomarkers for early diagnosis.Materials and methodsWe enrolled 100 patients including 13 healthy subjects, 12 non-AAs, 13 AAs, and 16 stage-I, 15 stage-II, 16 stage-III, and 15 stage-IV CRCs. These patients were classified as normal control, early neoplasia, and advanced neoplasia. The sEV proteome was explored by liquid chromatography-tandem mass spectrometry. Generalized association plots were used to integrate the clustering methods, visualize the data matrix, and analyze the relationship. The specific sEV biomarkers were identified by a decision tree via Orange3 software. Functional enrichment analysis was conducted by using the Ingenuity Pathway Analysis platform.ResultsThe sEV protein matrix was identified from the serum of 100 patients and contained 3353 proteins, of which 1921 proteins from 98 patients were finally analyzed. Compared with the normal control, subjects with early and advanced neoplasia exhibited a distinct proteomic distribution in the data matrix plot. Six sEV proteins were identified, namely, GCLM, KEL, APOF, CFB, PDE5A, and ATIC, which properly distinguished normal control, early neoplasia, and advanced neoplasia patients from each other. Functional enrichment analysis revealed that APOF+ and CFB+ sEV associated with clathrin-mediated endocytosis signaling and the complement system, which have critical implications for CRC carcinogenesis.ConclusionPatients with colorectal neoplasia had a distinct sEV proteome expression pattern in serum compared with those patients who were healthy and did not have neoplasms. Moreover, the six identified specific sEV proteins had the potential to discriminate colorectal neoplasia between early-stage and advanced neoplasia. Collectively, our study provided a six-sEV protein biomarker panel for CRC diagnosis at early or advanced stages. Furthermore, the implication of the sEV proteome in CRC carcinogenesis via specific signaling pathways was explored.

Dataset Information

Serum miR-21, miR-29a, and miR-125b Are Promising Biomarkers for the Early Detection of Colorectal Neoplasia.

Publications

Serum miR-21, miR-29a, and miR-125b Are Promising Biomarkers for the Early Detection of Colorectal Neoplasia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets